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                    <title><![CDATA[Ankylosing Spondylitis (as)]]></title>

                    <link>https://www.benthamscience.com</link>

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                    RSS Feed for Disease Wise Article | BenthamScience

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                    <pubDate>Sun, 08 Mar 2026 17:50:22 +0000</pubDate>

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                    <title><![CDATA[Ankylosing Spondylitis (as)]]></title>

                    <url>https://www.benthamscience.com</url>

                    <link>https://www.benthamscience.com</link>

                    </image><item><title><![CDATA[Spinal Cord Image Denoising Using Dncnn Algorithm]]></title><link>https://www.benthamscience.comarticle/146944</link><description><![CDATA[<p>Background: Spinal image denoising plays a vital role in the accurate diagnosis of disc herniation (DH). </p> <p> Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem. </p> <p> Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset. </p> <p> Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method. </p> <p> Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.</p>]]></description> </item><item><title><![CDATA[The Diagnostic Value of Abnormal Bone Marrow Signal Changes on Magnetic
Resonance Imaging: Is Bone Marrow Biopsy Essential?]]></title><link>https://www.benthamscience.comarticle/138997</link><description><![CDATA[<p>Background: It is essential to determine whether bone marrow signal changes on magnetic resonance imaging (MRI) represent a physiological response or pathology; at present, the clinical significance of these signal changes is unclear. It is unknown whether a bone marrow biopsy is required when bone marrow signal changes are detected incidentally in individuals without suspected malignancy. <p> Objective: The primary purpose of this study was to determine whether incidentally detected bone marrow signal changes on MRI performed for various reasons (at the time of admission or during follow-up) are clinically significant. <p> Methods: We retrospectively evaluated the bone marrow biopsy clinical and laboratory findings of 42 patients with incidental bone marrow signal changes on MRI between September 2016 and January 2020. We also determined whether the patients were diagnosed with malignancy during admission or follow-up. <p> Results: Of the 42 patients, three (7%) were diagnosed with hematological malignancies during admission, while two were diagnosed with multiple myeloma and one with B-cell acute lymphoblastic leukemia. Of the 42 patients, 35 had a mean follow-up of 40.6 ± 5.3 months. One patient was diagnosed with monoclonal gammopathy of undetermined significance four months after their first admission. <p> Conclusions: In addition to MRI, detailed clinical and laboratory evaluations should be performed to inform the decision for bone marrow biopsy and exclude hematological malignancy. If there is any doubt, a bone marrow biopsy should be performed. Moreover, since bone marrow signal changes may be a preliminary finding, follow-up of these patients is essential.</p>]]></description> </item><item><title><![CDATA[Value of Magnetic Resonance T1 Mapping in Evaluating the Early Response to
Treatment for Rheumatoid Arthritis]]></title><link>https://www.benthamscience.comarticle/135234</link><description><![CDATA[<p>Background: Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is usually used for the semi-quantitative evaluation of joint changes in Rheumatoid Arthritis (RA). However, this method cannot evaluate early changes in bone marrow edema (BME). <p> Objective: To determine whether T1 mapping of wrist BME predicts early treatment response in RA. <p> Methods: This study prospectively enrolled 48 RA patients administered oral anti-rheumatic drugs. MRI of the most severely affected wrist was performed before and after 4 (48 patients) and 8 weeks of treatment (38 patients). Mean T1 values of BME in the lunate, triangular, and capitate bones; RAMRIS for each wrist; Erythrocyte-Sedimentation Rate (ESR); and 28-joint Disease Activity Score (DAS28)-ESR score were analyzed. Patients were divided into responders (4 weeks, 30 patients; 8 weeks, 32 patients) and non-responders (4 weeks, 18 patients; 8 weeks, 6 patients), according to EULAR response criteria. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 values. <p> Results: ESR and DAS28-ESR were not correlated with T1 value and RAMRIS at each examination (P > 0.05). Changes in T1 value and DAS28-ESR relative to the baseline were moderately positively correlated with each other at 4 and 8 weeks (r = 0.555 and 0.527, respectively; P &#60; 0.05). At 4 weeks, the change and rate of change in T1 value significantly differed between responders and non-responders (-85.63 vs. -19.92 ms; -12.89% vs. -2.81%; P < 0.05). The optimal threshold of the rate of change in T1 value at 4 weeks for predicting treatment response was -5.32% (area under the ROC curve, 0.833; sensitivity, 0.900; specificity, 0.667). <p> Conclusion: T1 mapping provides a new imaging method for monitoring RA lesions; changes in wrist BME T1 values reflect early treatment response.</p>]]></description> </item><item><title><![CDATA[Efficacy and Mechanism of Highly Active Umbilical Cord Mesenchymal Stem Cells in the Treatment of Osteoporosis in Rats]]></title><link>https://www.benthamscience.comarticle/138338</link><description><![CDATA[<p>Background: Osteoporosis increases bone brittleness and the risk of fracture. Umbilical cord mesenchymal stem cell (UCMSC) treatment is effective, but how to improve the biological activity and clinical efficacy of UCMSCs has not been determined. </p> <p> Methods: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 10<sup>6</sup> cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κβ ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10<sup>-6</sup> mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, &#946;-catenin, RUNX2, IFN-&#947; and IL-17 in the bone tissue were measured via Western blotting. </p> <p> Results: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, &#946;-catenin, and runx2 was upregulated, and IFN-&#947; and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment. </p> <p> Conclusion: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/&#946;-catenin pathway and inhibition of inflammation.</p>]]></description> </item><item><title><![CDATA[Protective Effect of Statin Therapy in Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/137719</link><description><![CDATA[Ankylosing spondylitis (AS) is a complex autoimmune and auto-inflammatory disorder characterized by a gradual onset that can progress to spinal ankylosis over time. This chronic condition primarily affects the sacroiliac joints and the spine, often extending its influence to peripheral joints and extra-articular organs, including the eyes AS is associated with significant disability, along with comorbidities such as uveitis and inflammatory bowel disease. Moreover, individuals with AS face an elevated risk of mortality due to cardiovascular disease (CVD). This paper explores the potential benefits of statins, known for their anti-inflammatory and immunomodulatory effects, in mitigating AS-related cardiovascular risk and their therapeutic effects on disease activity.]]></description> </item><item><title><![CDATA[Mechanisms of Stem Cells and Their Secreted Exosomes in the Treatment of Autoimmune Diseases]]></title><link>https://www.benthamscience.comarticle/137044</link><description><![CDATA[Stem cells play a therapeutic role in many diseases by virtue of their strong self-renewal and differentiation abilities, especially in the treatment of autoimmune diseases. At present, the mechanism of the stem cell treatment of autoimmune diseases mainly relies on their immune regulation ability, regulating the number and function of auxiliary cells, anti-inflammatory factors and proinflammatory factors in patients to reduce inflammation. On the other hand, the stem cell- derived secretory body has weak immunogenicity and low molecular weight, can target the site of injury, and can extend the length of its active time in the patient after combining it with the composite material. Therefore, the role of secretory bodies in the stem cell treatment of autoimmune diseases is increasingly important.]]></description> </item><item><title><![CDATA[The Epigenetic Contribution to the Pathogenesis of Psoriasis: Recent
Advances]]></title><link>https://www.benthamscience.comarticle/131442</link><description><![CDATA[Psoriasis is defined as a chronic autoimmune disorder of the skin in which abnormal proliferation and differentiation of keratinocytes are blamed as the central culprit of disease etiopathogenesis. A complex interplay between environmental factors and genetic risk factors has been suggested to trigger the disease. However, epigenetic regulation appears to connect external stimuli and genetic abnormalities in the development of psoriasis. The discordance in the prevalence of psoriasis between monozygotic twins and environmental factors that contribute to its onset have caused a paradigm shift regarding the mechanisms underlying the pathogenesis of this disease. Epigenetic dysregulation may be involved in aberrancies of keratinocyte differentiation, T-cell activation, and other plausible cells, leading to the initiation and perpetuation of psoriasis. Epigenetics is characterized by heritable alterations in the transcription of genes without nucleotide change and is commonly considered at three levels, i.e., DNA methylation, histone modifications, and microRNAs. To date, scientific evidence has indicated abnormal DNA methylation, histone modifications, and non-coding RNA transcription in psoriatic patients. In order to reverse aberrant epigenetic changes in psoriasis patients, several compounds and drugs (epi-drugs) have been developed to affect the major enzymes involved in the methylation of DNA, or the acetylation of histones, which aim to correct the aberrant methylation and acetylation patterns. A number of clinical trials have suggested the therapeutic potential of such drugs in the treatment of psoriasis. In the present review, we attempt to clarify recent findings with respect to epigenetic irregularities in psoriasis and discuss future challenges.]]></description> </item><item><title><![CDATA[Tumor Necrosis Alpha (TNF-&#945;) Antagonists Used in Chronic Inflammatory
Rheumatic Diseases: Risks and their Minimization Measures]]></title><link>https://www.benthamscience.comarticle/137135</link><description><![CDATA[Tumor necrosis factor alpha (TNF- &#945;) inhibitors are widely employed for the management of chronic inflammatory rheumatism. However, their usage carries significant risks, including site and infusion reactions, serious infections, malignancy, heart failure autoimmune and demyelinating disorders. These risks are comprehensively outlined in risk management plans (RMPs) associated with these molecules. RMP provides information on the safety profile of a medicinal product as well as the measures that will be taken to minimize risks; these are known as risk minimization measures. These measures are divided into routine measures related to elements, such as the summary of product characteristics, labeling, pack size, package leaflet, or legal supply status of the product, while additional measures may include educational programs, including tools for healthcare providers and patients, controlled access or pregnancy prevention programs, among others. Additional measures can consist of one or more interventions that need to be implemented in a sustainable way in a defined target group, while respecting the timing and frequency of any intervention and procedures to reach the target population. An evaluation of the effectiveness of these measures is required to determine whether or not an intervention has been effective. This comprehensive review offers an in-depth exploration of the current treatment, uses, and associated risks of TNF-&#945; inhibitors. Additionally, it provides a detailed account of risk minimization measures and risk management practices while shedding light on their real-world implementation and effectiveness.]]></description> </item><item><title><![CDATA[An Overview of Adalimumab Therapy for Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/138799</link><description><![CDATA[<p>Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease known for causing pain, stiffness, and reduced mobility in the axial skeleton. Adalimumab, a tumor necrosis factor (TNF) inhibitor, has emerged as a promising therapeutic option for AS. <p> Methods: This systematic review involved a comprehensive search of randomized controlled trials related to AS treatment, conducted in major databases such as MEDLINE, Google Scholar, and PubMed. The search terms encompassed ankylosing spondylitis, adalimumab, methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics. A total of 14 randomized controlled trials with 4,500 participants were included in the review. <p> Results: The review's results revealed that adalimumab demonstrated notable superiority when compared to a placebo. It effectively reduced disease activity, improved physical function, and lowered inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Adalimumab demonstrated a favorable safety profile, with adverse events comparable to those observed with placebo. <p> Conclusion: Based on the results, adalimumab is deemed an effective treatment for AS, showcasing its potential as a first-line therapeutic option. Notably, no significant increase in adverse events was observed compared to placebo. However, the conclusion emphasizes the need for further studies with extended follow-up durations to ascertain the long-term efficacy and safety of adalimumab in AS management. This systematic review provides valuable insights supporting the use of adalimumab in the treatment of AS and underscores the importance of ongoing investigations into its long-term effects to optimize its clinical utilization in AS patients.</p>]]></description> </item><item><title><![CDATA[Study on the Expression and Potential Function of LncRNA in Peripheral
Blood of Patients with Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/138381</link><description><![CDATA[<p>Background: Ankylosing spondylitis (AS) is an autoimmune disease that has the characteristics of difficult early diagnosis and a high disability rate. <p> Objective: The objective of this study was to further explore the possible mechanism and potential function of lncRNA in AS. <p> Methods: We used lncRNA microarray technology to detect the expression of lncRNA and mRNA in patients with active AS, stable patients, and healthy controls (HC). Afterward, bioinformatics analysis was conducted on differentially expressed genes. Seven differentially expressed lncRNAs were screened out for real-time fluorescent quantitative PCR (RT-qPCR), combined with various clinical indicators for correlation analysis, and the receiver operating characteristic (ROC) curve was used to analyze the potential of lncRNA as a diagnostic marker for AS. <p> Results: The results showed that the expression levels of NR-037662 and ENST00000599316 in the AS subgroups were significantly higher than those in the HC group, while the expression levels of ENST00000577914 and ENST00000579003 were lower than those in the HC group. The expression levels of NR-003542 and ENST00000512051 in the ASA group were significantly higher than those in the ASS and HC groups, while NR-026756 was just the opposite. Spearman’s correlation analysis showed that the expression level of NR-003542 was positively correlated with Bath Ankylosing Spondylitis Functional Index (BASFI), Erythrocyte Sedimentation Rate (ESR), and high sensitivity C-Reactive Protein (hsCRP). The expression level of NR-026756 was negatively correlated with the Bath Ankylosing Spine Inflammatory Disease Activity Index (BASDAI), BASFI, ESR, hsCRP, and globulin (GLOB). In addition, it was also found that the ROC curve analysis of the 4 lncRNAs between the AS group (ASA group and ASS group) and the HC group were statistically significant, and the area under the curve (AUC) of NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 was 0.804, 0.812, 0.706, and 0.698, respectively. <p> Conclusion: It was found that these differentially expressed lncRNAs of AS may be involved in the occurrence and development of the disease. Among them, NR-037662, ENST00000599316, ENST00000577914, and ENST00000579003 might have the potential to become AS diagnostic molecular markers. Moreover, NR -003542, ENST00000512051, and NR-026756 might have the potential to be indicators of disease activity.</p>]]></description> </item><item><title><![CDATA[Hypoparathyroidism: Musculoskeletal Manifestations Related to
Parathormone Deficiency]]></title><link>https://www.benthamscience.comarticle/137847</link><description><![CDATA[<p>Background: Hypoparathyroidism is a rare metabolic disorder that can be responsible for musculoskeletal manifestations. <p> Aim: We present a systematic review of musculoskeletal manifestations of adult-onset nonsurgical nongenetic hypoparathyroidism. <p> Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE database, including manuscripts describing musculoskeletal manifestations of adult-onset nonsurgical nongenetic hypoparathyroidism. <p> Results: Musculoskeletal manifestations included myopathy, shoulder disorder, immune-negative non-erosive peripheral arthritis, axial involvement simulating spondylarthritis, and diffuse ligamentous ossifications. An association between hypoparathyroidism and spondyloarthritis or autoimmune diseases is possible. T-cell activation, seen in patients with hypoparathyroidism, may explain the co-occurrence of hypoparathyroidism with other autoimmune diseases. <p> The treatment of these manifestations is based on calcium and active vitamin D supplementation. Parathyroid hormone may have an anabolic effect on muscle atrophy and muscle weakness. Parathyroid hormone can also promote bone formation and bone resorption by stimulating osteoclast differentiation by increasing RANKL (receptor activator for nuclear factor kappa-B ligand) expression. Therefore, hypoparathyroidism can be responsible for an increase in bone mineral density. However, the risk of fractures does not appear to be reduced due to changes in bone microarchitecture and the high risk of falls. Treatment with parathyroid hormone has been shown to improve bone microarchitecture. <p> Conclusion: Our review showed that musculoskeletal manifestations are frequent in patients with hypoparathyroidism, including muscular, axial, peripheral articular, and entheseal manifestations.</p>]]></description> </item><item><title><![CDATA[Insight into the Epidemiology of the Adult-onset Systemic Autoimmune
Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients]]></title><link>https://www.benthamscience.comarticle/137429</link><description><![CDATA[<p>Background/Objective: Although systemic autoimmune rheumatic diseases (SARDs) seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity of data compared with the developed countries. Furthermore, most of the studies addressed a particular disease. This work aimed to shed light on the relative frequency and epidemiology of the different adult-onset SARDs in Egypt. <p> Methods: This is a retrospective hospital-based study including six university hospitals providing free health care services: Cairo, Alexandria, Tanta, Suez Canal, Beni-Suef and Assiut University Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient departments between January 2000 and December 2021 were retrospectively reviewed. Data about the patient’s diagnosis, gender, age at disease onset, year of disease onset and residence were collected. <p> Results: The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behçet’s disease (BD) and spondyloarthropathies (SPA) represented the main SARDs in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect females; males are mainly affected by axial SPA and BD. There is an increasing incidence of SARDs during the study period. <p> Conclusion: The study revealed the high burden of SARDs in Egypt, helping better allocation of economic resources for the management of diseases of the highest prevalence and those affecting the young reproductive age groups. Increased public and medical staff awareness about SARDs is recommended to help early referral of patients to rheumatologists and, hence, better estimation of their epidemiology.</p>]]></description> </item><item><title><![CDATA[Effect of Dexketoprofen on the Disposition Kinetics of Moxifloxacin in Plasma and
Lung in Male and Female Rats]]></title><link>https://www.benthamscience.comarticle/137553</link><description><![CDATA[<p>Background: The simultaneous use of NSAIDs and antibiotics is recommended for bacterial diseases in human and veterinary medicine. Moxifloxacin (MFX) and dexketoprofen (DEX) can be used simultaneously in bacterial infections. However, there are no studies on how the simultaneous use of DEX affects the pharmacokinetics of MFX in rats. <p> Objectives: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics of MFX in male and female rats. <p> Methods: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the highperformance liquid chromatography-UV and pharmacokinetic parameters were evaluated by noncompartmental analysis. <p> Results: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to 8 h (AUC<sub>0-8</sub>) and peak concentration (C<sub>max</sub>) of MFX in rats, while it significantly decreased the total body clearance (CL/F). When female and male rats were compared, significant differences were detected in AUC<sub>0-8</sub>, C<sub>max</sub>, CL/F and volume of distribution. The AUC<sub>0-8lung</sub>/AUC<sub>0-8plasma</sub> ratios of MFX were calculated as 1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively. <p> Conclusion: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats but did not change its passage to the lung. However, there is a need for a more detailed investigation of the difference in the pharmacokinetics of MFX in male and female rats.</p>]]></description> </item><item><title><![CDATA[Is there an Association between Complementary and Alternative Medicine
use and Trust in Physicians in Patients with Rheumatic Diseases?]]></title><link>https://www.benthamscience.comarticle/137202</link><description><![CDATA[<p>Introduction: Generally, patients with chronic rheumatic diseases use complementary and alternative medicine (CAM) in addition to their conventional treatments to manage their health. Discussing these treatments with their physician is still rare, which might be directly related to patients’ trust toward them. <p> Aim: The primary objective of this study was to assess the association between patients’ trust in their physician and the use of complementary and alternative medicine among patients with chronic inflammatory rheumatic diseases. As secondary objectives, to estimate the prevalence of CAM use, and to identify the associated factors with their use and with trust in physicians. <p> Methods: This is a cross-sectional study, which included patients with established chronic inflammatory rheumatic diseases, at the University Hospital Center in Tangier. The questionnaire included demographic and clinical information, use of conventional therapy, complementary and alternative therapy, as well as interpersonal trust in patient-physician relationships using the Trust in Physician Scale (TPS). A regression analysis was conducted to identify factors associated with CAM use and with trust in physicians. <p> Results: The study included 189 patients. 57.14% of patients reported using complementary medicine at least once, most patients were women (77.78%), mean age was 46.67 ± 13.25 years with an average course of the disease of 11.11 ± 9.23 years. The most frequently used CAM treatments were cupping therapy, massage and the ingestion of a mixture of plants. Mean ± SD Trust in Physician Scale was 47.64 ± 7.2. There was no significant difference between CAM users vs. non-users (48.08 ± 6.9 vs 47.04 ± 7.4; p = 0.35). In uni and multivariate analysis, a low level of education was significantly associated with the use of CAM. However, no statistically significant difference was found with trust in physicians (OR = 1.020, 95% CI (0.978-1.063), p = 0.354). <p> Conclusion: CAM therapy is common in patients with chronic inflammatory rheumatic diseases. No statistically significant association was found with trust in physicians, it was rather observed with level of education.</p>]]></description> </item><item><title><![CDATA[No Correlation between Anti-drug Antibodies and Therapeutic Response
in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF
Blockers]]></title><link>https://www.benthamscience.comarticle/136906</link><description><![CDATA[<p>Introduction: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response. <p> Methods: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA). <p> Results: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p &#60; 0.01 and p &#60; 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity. <p> Conclusion: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.</p>]]></description> </item><item><title><![CDATA[Balance Impairment in Patients with Rheumatoid Arthritis and
Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/134111</link><description><![CDATA[<p>Background: Balance weaknesses related to mobility and fall risk in patients with rheumatic diseases are well-known. Vestibular dysfunction could negatively contribute to the balance ability of this patient population. This study aims to investigate the effects of Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS), among the most common rheumatic diseases, on postural balance related to vestibular function. <p> Methods: Seventy-eight participants were grouped as RA (n=34, 43%), AS (n=24, 30.7%), and the control group consisted of healthy individuals (n=20, 25.6%). Cervical Vestibular Evoked Myogenic Potentials (cVEMP) test, which assesses the vestibular function objectively, Dizziness Handicap Inventory (DHI), which evaluates vertigo subjectively, and Berg Balance Scale (BBS) were performed. <p> Results: Different degrees of VEMP latency prolongations were found in the AS and RA groups. Right, and left ear N1 latencies were significantly longer in the AS group than in RA and control. Right ear P1 latency prolongation was statistically significant in the RA group. Amplitude asymmetry ratio (AAR) was found to be considerably higher in the RA and AS groups than in the control group (p &#60; 0.05). The mean BBS score in the AS group was below the fall risk score of 45. A negative statistically significant effect was observed between latency prolongation and BBS in AS groups. <p> Conclusion: The abnormal VEMP findings in individuals with RA and AS shows inner ear vestibular system dysfunction. This vestibular impairment strictly contributes to their postural imbalance and requires a focused vestibular rehabilitation program for balance treatment.</p>]]></description> </item><item><title><![CDATA[A Review of the Occurrence of Rheumatoid Arthritis and Potential
Treatments through Medicinal Plants from an Indian Perspective]]></title><link>https://www.benthamscience.comarticle/136368</link><description><![CDATA[<p>Arthritis is a medical condition that affects the joints and causes inflammation, pain, and stiffness. There are different types of arthritis, and it can affect people of all ages, even infants and the elderly. Recent studies have found that individuals with diabetes, heart disease, and obesity are more likely to experience arthritis symptoms. According to the World Health Organization, over 21% of people worldwide suffer from musculoskeletal problems. Roughly 42.19 million individuals in India, constituting around 0.31% of the populace, have been documented as having Rheumatic Arthritis (RA). <p> Compared to other common diseases like diabetes, cancer, and AIDS, arthritis is more prevalent in the general population. Unfortunately, there is no specific cure for arthritis, and treatment plans usually involve non-pharmacological methods, surgeries, and medications that target specific symptoms. Plant-based remedies have also been shown to be effective in managing inflammation and related complications. In addition to therapies, maintaining a healthy diet, exercise, and weight management are essential for managing arthritis. <p> This review discusses the causes, prevalence, diagnostic methods, current and prospective future treatments, and potential medicinal plants that may act as anti-inflammatory or anti-rheumatic agents. However, more research is necessary to identify the underlying mechanisms and active molecules that could improve arthritis treatment.</p>]]></description> </item><item><title><![CDATA[Association of Autoimmune Disorders and Disease-modifying
Antirheumatic Drugs: (DMARDs) with the Risk of Alzheimer’s and/or
Dementia: A Population Study Using Medicare Beneficiary Data]]></title><link>https://www.benthamscience.comarticle/138074</link><description><![CDATA[<p>Objectives: Alzheimer’s disease (AD) and/or dementia is a prevalent neurocognitive disorder primarily affecting individuals over the age of 65. Identifying specific causes of AD and/or dementia can be challenging, with emerging evidence suggesting a potential association with autoimmune inflammatory conditions such as rheumatoid arthritis (RA). This study aimed to assess the prevalence rate of AD and/or dementia among Medicare beneficiaries reporting an autoimmune disorder. Additionally, this study sought to identify the comparative prevalence of AD and/or dementia in patients with an autoimmune disorder who were using disease-modifying antirheumatic drugs (DMARDs) compared to those not using DMARDs. <p> Methods: Cross-sectional secondary data analyses were conducted on Medicare Current Beneficiary Survey (MCBS) data from 2017 and 2018. The MCBS data consists of a nationally representative sample of the Medicare population, a population that is largely 65 and older, and provides de-identified patient information. Patients from this dataset with a self-reported autoimmune disorder were included in the analyses. Descriptive analyses were conducted on demographic variables, chronic conditions, and medication use. The prevalence of AD and/or dementia was compared between patients with and without an autoimmune disorder. A backward stepwise selection regression was used to identify the risk factors associated with the prevalence of AD and/or dementia. <p> Results: The study included 18,929 Medicare beneficiaries, with 4,405 identified as having one autoimmune disorder. The prevalence of AD and/or dementia was significantly higher in patients with an autoimmune disorder. The multivariate regression showed that RA was significantly associated with a higher risk of AD and/or dementia. Other demographic factors, including advanced age, African-American or Hispanic ethnicity, low body mass index, and chronic conditions of ischemic heart disease, history of myocardial infarction, history of stroke, depression, mental health disorder(s), and traumatic brain injury also showed statistically significant associations with AD and/or dementia. Patients using DMARDs demonstrated a reduced likelihood of having AD and/or dementia, compared to patients not using DMARDs. <p> Conclusion: This study provides evidence of an association between RA and increased risk of AD and/or dementia. The findings suggest that DMARD use may have a protective effect against the development of AD and/or dementia in patients with an autoimmune disorder.</p>]]></description> </item><item><title><![CDATA[Potential Roles for B cells and Autoantibodies in Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/135454</link><description><![CDATA[<P>Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease that predominantly affects young males. AS is a condition in which the spine and sacroiliac joints become inflamed. More specifically, most AS patients experience spine malformations over time, resulting in functional incapability. The etiopathogenesis of AS is a complex combination of genetic predisposition and environmental factors. Extensive studies on AS have revealed the central role of genetics and immune reactions in its etiology. However, an utmost agreement has yet to be created. The available evidence suggests that both autoinflammation and T-cell-mediated autoimmune processes have significant roles in the disease process of AS. So far, B cells have obtained moderately little attention in AS pathogenesis, primarily because of the absence of disease-defining autoantibodies. However, against general dogma, evidence is mounting showing B cell involvement. Disruptions depict this in circulating B cell populations, the increased expression of immunoglobulin (Ig)G, IgA, and IgM, and B cell infiltration within the axial skeleton of AS patients. <P> Meanwhile, compared to many other inflammatory autoimmune disorders, AS has no disease-specific autoantibodies that help disease diagnosis. This study has provided an overview of the B lymphocytes and antibodies' role in AS pathogenesis. It also introduces autoantibodies that can be the prognosis and diagnosis biomarkers of AS.</P>]]></description> </item><item><title><![CDATA[Axial Involvement in Psoriatic Arthritis: A Cross-sectional Clinical and
Radiologic Studies]]></title><link>https://www.benthamscience.comarticle/134392</link><description><![CDATA[Objective: This study aimed to investigate spinal involvement in psoriatic arthritis (PsA) patients using clinical and radiographic methods. </P> <P> Methods: A cross-sectional clinical study was conducted on 50 PsA patients diagnosed according to the CASPAR criteria. Clinical examinations and functional assessments were performed. A radiographic assessment of the spine was performed. </P> <P> Results: Out of 50 PsA patients (mean age of 45.50 ± 9.90 years), (males and females constituted 27 (54.0%) and 23 (46.0%) respectively), 76% had radiological axial involvement; (26%) with inflammatory axial pain and (50%) without inflammatory axial pain (subclinical). Three axial radiographic patterns were detected including spondylitis without sacroiliitis (15.78%), spondylitis with sacroiliitis (78.94%), and sacroiliitis without spondylitis (5.26%). </P> <P> In axial PsA patients, males were more affected than females (&#967;<sup>2</sup>=11.679, <i>p</i> = 0.003), with older age (H = 15.817, <i>p</i> < 0.001) and higher body mass index (BMI) (F = 5.145, <i>p</i> = 0.010), increased psoriasis duration (H = 9.826, <i>p</i> = 0.007) and severity (Η=25.171, <i>p</i> &#60; 0.001), and more spinal movement limitations than PsA patients without axial involvement (F = 26.568, <i>p</i> &#60; 0.001). </P> <P> Cervical involvement was higher than lumbar involvement. Axial radiographic severity assessed by the PsA Spondylitis Radiology Index was associated with increased disability as assessed by the Health assessment questionnaire (r<sub>s</sub> = 0.533, p = 0.001) and decreased quality of life assessed by short form-36 score (r<sub>s</sub> = -0.321, <i>p</i> = 0.050). </P> <P> Conclusion: This study shows that a high percentage of PsA patients had axial involvement with a high percentage of them having asymptomatic radiological findings. The cervical spine is more frequently and severely affected than the lumbar spine. Axial PsA occurs in males more than females with characteristic older age and higher BMI, increased psoriasis duration, and more limitation of spinal mobility.</P>]]></description> </item><item><title><![CDATA[A Comprehensive Review on Management and Treatment of Arthritis Specially
Emphasizing Treatment with Transdermal Patch]]></title><link>https://www.benthamscience.comarticle/135966</link><description><![CDATA[Arthritis is one of the major inflammatory diseases and is a global issue. Arthritis is currently an utmost public health problem and it severely affects impact the life of the geriatric population. There are several types of arthritis such as Rheumatoid arthritis, Osteoarthritis, Gout, and Fibromyalgia, which limit the mobility of the patient. In most cases, the reason for the disease is not known clearly and available treatment can reduce the symptoms but cannot cure it completely. Though Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), glucocorticoids, and Disease Modifying Anti Rheumatic Drugs (DMARDs) are the first-line treatments available in arthritis, gastrointestinal discomfort, low solubility, strong first-pass metabolism, low bioavailability, and systemic adverse reactions are the main drawbacks related to these drugs when used in long-term. Based on the evidence related to side effects of the current treatment methodology, several recent studies and developments have been designed and summarized in this field. From these studies, it has been observed that the transdermal drug delivery system can minimize the side effects associated with the oral dosage forms and can deliver the drug directly to the target site along with controlled and prolonged drug release. Hence, novel approaches in transdermal drug delivery systems like transdermal patches and microneedle therapy could be an alternative approach in the treatment and management of arthritis.]]></description> </item><item><title><![CDATA[Herbal Technological Prospects of <i>Morus nigra</i> L.: A Systematic
Patent Analysis Review]]></title><link>https://www.benthamscience.comarticle/133842</link><description><![CDATA[<p> Background: <i>Morus nigra</i> L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. <p> Objectives: This article aims to compile the technological perspectives of <i>Morus nigra</i> L. towards drug development and therapeutic indications based on registered patents in databases. <p> Methods: The study analyzed patents published within the last five years, focusing on products derived from different parts of the <i>Morus nigra</i> L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. <p> Results: A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. <p> Conclusion: The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.</p>]]></description> </item><item><title><![CDATA[Yuflyma, A High Concentration and Citrate-free Adalimumab Biosimilar,
Received FDA Approval for Treating Different Forms of Inflammato ry
Diseases]]></title><link>https://www.benthamscience.comarticle/136243</link><description><![CDATA[]]></description> </item><item><title><![CDATA[Inflammation and Mental Health Disorders: Immunomodulation as a Potential
Therapy for Psychiatric Conditions]]></title><link>https://www.benthamscience.comarticle/136014</link><description><![CDATA[Mood disorders are the leading cause of disability worldwide and their incidence has significantly increased after the COVID-19 pandemic. Despite the continuous surge in the number of people diagnosed with psychiatric disorders, the treatment methods for these conditions remain limited. A significant number of people either do not respond to therapy or discontinue the drugs due to their severe side effects. Therefore, alternative therapeutic interventions are needed. Previous studies have shown a correlation between immunological alterations and the occurrence of mental health disorders, yet immunomodulatory therapies have been barely investigated for combating psychiatric conditions. In this article, we have reviewed the immunological alterations that occur during the onset of mental health disorders, including microglial activation, an increased number of circulating innate immune cells, reduced activity of natural killer cells, altered T cell morphology and functionality, and an increased secretion of pro-inflammatory cytokines. This article also examines key studies that demonstrate the therapeutic efficacy of anti-inflammatory medications in mental health disorders. These studies suggest that immunomodulation can potentially be used as a complementary therapy for controlling psychiatric conditions after careful screening of candidate drugs and consideration of their efficacy and side effects in clinical trials.]]></description> </item><item><title><![CDATA[Quality by Design Approach for Preparation, Characterization, and Statistical
Optimization of Naproxen Sodium-loaded Ethosomes <i>via</i> Transdermal
Route]]></title><link>https://www.benthamscience.comarticle/132331</link><description><![CDATA[<p>Aim: The primary goal of this study is to create a novel naproxen sodium-loaded ethosome drug delivery system for improving bioavailability, solubility and optimize using a statistical approach. <p> Background: Naproxen sodium (i.e., a non-steroidal anti-inflammatory drug) is chosen as the first line of treatment for rheumatoid arthritis and ankylosing spondylitis. However, naproxen has side effects, such as bronchospasm, an irregular heart rhythm, etc. Therefore, adopting new drug delivery strategies when developing the dosage form is necessary and the need of the hour to prevent its side effects. The available commercial products are administered through the oral and parenteral routes, which lack bioavailability and permeability respectively. <p> Objective: Novel ethosomal carriers were designed using Box Behnken Design (BBD) and formulation was prepared for enhanced topical delivery of naproxen sodium ethosomal gel. <p> Methods: In order to analyze the data statistically and graphically with response surface plots, the Box-Behnken design was used to optimize the formulation variables. The independent factors were phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3), while the dependent variables were entrapment efficiency (Y2), vesicle size (Y1), and PDI (Y3). The Carbopol® 940 gel was then made using the improved ethosomes. Its rheological properties, in-vitro release, ex-vivo skin penetration, and deposition were studied. <p> Results: The best ethosomes were made by mixing phosphatidylcholine and cholesterol in a phosphate buffer at pH 7.4 with 2–5% v/v ethanol. The optimized ethosomes showed a zeta potential of -32.06 ± 0.16 mV, EE of 84.59 ± 2.38%, and a vesicular size of 105 ± 6.97 nm. Compared to the commercial products and the ethanolic solution of naproxen, these ethosomes considerably increased the amount of naproxen permeated through the skin over 24 hours. The stability of the optimized formulation was assessed for three months at room temperature, and it was found that the efficiency of the prepared novel ethosomal formulation remained intact. <p> Conclusion: In summary, it was discovered that the ethosomal vesicles were potential carriers, showing the improved topical distribution of naproxen sodium. These findings demonstrated that using ethosomes as a transdermal medication carrier for naproxen was feasible. Compared to drug solutions, the ex-vivo permeation and skin deposition experiments produced better results.</p>]]></description> </item><item><title><![CDATA[Role of Th17 and IL-17 Cytokines on Inflammatory and Auto-immune Diseases]]></title><link>https://www.benthamscience.comarticle/134257</link><description><![CDATA[<P>Background: The IL-17 (interleukin 17) family consists of six structurally related pro-inflammatory cytokines, namely IL-17A to IL-17F. These cytokines have garnered significant scientific interest due to their pivotal role in the pathogenesis of various diseases. Notably, a specific subset of T-cells expresses IL-17 family members, highlighting their importance in immune responses against microbial infections. </P><P> Introduction: IL-17 cytokines play a critical role in host defense mechanisms by inducing cytokines and chemokines, recruiting neutrophils, modifying T-cell differentiation, and stimulating the production of antimicrobial proteins. Maintaining an appropriate balance of IL-17 is vital for overall health. However, dysregulated production of IL-17A and other members can lead to the pathogenesis of numerous inflammatory and autoimmune diseases. </P><P> Method: This review provides a comprehensive overview of the IL-17 family and its involvement in several inflammatory and autoimmune diseases. Relevant literature and research studies were analyzed to compile the data presented in this review. </P><P> Results: IL-17 cytokines, particularly IL-17A, have been implicated in the development of various inflammatory and autoimmune disorders, including multiple sclerosis, Hashimoto's thyroiditis, systemic lupus erythematosus, pyoderma gangrenosum, autoimmune hepatic disorders, rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, osteoarthritis, and graft-<i>versus</i>-host disease. Understanding the role of IL-17 in these diseases is crucial for developing targeted therapeutic strategies. </P><P> Conclusion: The significant involvement of IL-17 cytokines in inflammatory and autoimmune diseases underscores their potential as therapeutic targets. Current treatments utilizing antibodies against IL-17 cytokines and IL-17RA receptors have shown promise in managing these conditions. This review consolidates the understanding of IL-17 family members and their roles, providing valuable insights for the development of novel immunomodulators to effectively treat inflammatory and autoimmune diseases.</P>]]></description> </item><item><title><![CDATA[MicroRNAs in the Pathogenesis of Ankylosing Spondylitis and
their Clinical Implication]]></title><link>https://www.benthamscience.comarticle/127388</link><description><![CDATA[Ankylosing spondylitis (AS) is a chronic and progressive immunoinflammatory disease, which mainly affects the spine and sacroiliac joints and shows a high rate of late disability. Inflammation, bone destruction, and new bone formation are typical pathological changes of AS. AS is dominated by inflammation at the early stage. While bone destruction and heterotopic ossification, the two contradictory manifestations of AS, occur at a later stage and reflect the imbalance between osteogenesis and osteoclastogenesis in AS patients. Till now, the pathogenesis of AS remains unclear. MicroRNAs (miRNAs) are a class of highly conserved single-stranded noncoding RNAs (ncRNAs) with a length of about 22 bases characterized by temporal sequence and tissue specificity. MiRNAs are key modulators in bone formation, resorption, remodeling and regeneration by regulating the immune responses and the differentiation and functions of osteoblasts, osteoclasts and chondrocytes. The present review summarizes the roles and potential mechanisms of miRNAs’ involvement in AS by regulating immuno-inflammatory responses, bone destruction, heterotopic ossification, cell death and autophagy, and the involved signaling including the Wnt/&#946;-catenin and BMP/Smads pathways. In addition, the feasibility of miRNAs as diagnostic biomarkers and therapeutic targets for AS are also discussed.]]></description> </item><item><title><![CDATA[Translation and French Linguistic Validation of the Bath Ankylosing
Spondylitis Functional Index and the Bath Ankylosing Spondylitis Global
Score in Patients with Axial Spondyloarthritis]]></title><link>https://www.benthamscience.comarticle/125971</link><description><![CDATA[<p>Background: Axial spondyloarthritis (axSpA) may lead to functional and physical disturbances. Self-administered questionnaires can measure functional limitations associated to axSpA. If these questionnaires are currently used in clinical practice and research, the French version of these questionnaires has not been validated. The aim of this study was to translate and perform a linguistic validation of the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global score (BAS-G) in French. <p> Methods: The study has been approved by local ethic committee and is registered in Clinical Trial (NCT04212806). The translation process was performed through a forward/backward validation process, followed by clinician experts validation and patient cognitive interviews. <p> Results: The two questionnaires were translated into a French version by two independent translators. Translators then agreed on sentences being different between the two translations. The backward translation was equivalent to the initial English version except for two questions. Five French clinician experts on rheumatology made essential changes in sentences constructions of the translated questionnaire. The last version of the questionnaires was presented to 5 patients with axSpA which all found them clear and understandable. <p> Conclusion: BASFI and BAS-G would be a generally reliable instrument for patients with axSpA. These questionnaires can be widely used in clinical practice and research in French-speaking population. The use of these questionnaires is expected to have a positive impact on patient care to better understand physical consequences of axSpA.</p>]]></description> </item><item><title><![CDATA[Clinical Application and Synthesis Methods of Deuterated Drugs]]></title><link>https://www.benthamscience.comarticle/127749</link><description><![CDATA[Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.]]></description> </item><item><title><![CDATA[Necrotizing Scleritis and Rheumatoid Arthritis: A Clinical Case Report
Supported by A Brief Review with Risk of Bias Analysis]]></title><link>https://www.benthamscience.comarticle/129682</link><description><![CDATA[<p>Introduction: Necrotizing scleritis (NS) presents 30%-40% as having a systemic autoimmune condition. <p> Objective: To present a clinical case report and a systematic review of necrotizing scleritis with ocular manifestation as the first sign of rheumatologic disease. <p> Methods: The present study was elaborated according to the rules of CARE. <p> Case Report: A female patient, 63 years old, a white, administrative assistant, presented irritation, low visual acuity (LVA) in the left eye (LE), and headache. Biomicroscopy (BIO) in the right eye (RE) was normal, and the LE showed hyperemia and scleral thinning. After 1 month, the patient returns without signs of infectious diseases in the exams, and after a rheumatological evaluation with a diagnosis of rheumatoid arthritis, methotrexate and prednisone are prescribed. After 2 months, she relapsed and started treatment with anti-TNF, with remission after the 4th dose. After 1 year, she evolved with LVA in LE. <p> Results: A total of 244 articles were found, 104 articles were evaluated and 10 were included in the brief review. The symmetrical Funnel Plot does not suggest a risk of bias. <p> Conclusion: Both in the present case report and the literary findings, it was evidenced that the ophthalmologic findings may precede the systemic changes of the disease for the early diagnosis of rheumatoid arthritis.</p>]]></description> </item><item><title><![CDATA[Association of microRNA-146a rs57095329 Polymorphism with Susceptibility
to Primary Gout in a Chinese Han Population]]></title><link>https://www.benthamscience.comarticle/129502</link><description><![CDATA[<p>Background: MicroRNA-146a (miR-146a) plays a critical role in the regulation of autoinflammatory diseases, including gout. There is growing evidence that miR-146a gene single nucleotide polymorphisms (SNPs) are associated with different diseases, but no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. <p> Objective: The purpose of this study was to examine the relationship between the miR-146a rs57095329 genetic polymorphism and the susceptibility to primary gout in the Chinese Han population. <p> Methods: A case-control study was performed in this report to examine the potential association between gout and the functional rs57095329 SNP of miR-146a in a Chinese population consisting of 448 primary gout patients (containing 76 tophi patients) and 418 healthy controls. MiR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured in 81 gout patients (including 32 tophi patients and 49 non-tophi patients) and 47 healthy subjects. <p> Results: There was no significant difference found in the distribution of miR-146a rs57095329 between 448 gout patients and 418 healthy subjects (P > 0.05). However, significant differences in genotypes and allele distributions were found between 76 gout with tophi patients and 418 healthy subjects, as well as between gout with tophi (76) and with no tophi patients (372) (P < 0.01, respectively). Gout patients with AG/GG genotypes had a 0.323-fold reduced risk for tophi than those with the AA genotype, and the G allele had a 0.362-fold reduced risk of tophi. Furthermore, in 32 tophi patients, the GG genotype was significantly associated with increased expression of miR- 146a. <p> Conclusion: Our findings suggest that rs57095329 may play a protective role in tophi gout susceptibility, and rs57095329 A > G variant may modulate the expression of miR-146a in tophi patients.</p>]]></description> </item><item><title><![CDATA[COVID-19 in Patients with Systemic Inflammatory Diseases: Impact on
Disease Activity]]></title><link>https://www.benthamscience.comarticle/128872</link><description><![CDATA[<P>Introduction: COVID-19 pandemic, an international emergency, raised concerns about the interaction of this infection and disease-modifying drugs used in the treatment of Systemic inflammatory diseases (SID). Understanding the relationship between COVID-19 and disease activity is crucial to adapt the treatment. <P> Aim: The aim of our study was to determine the impact of COVID-19 on the disease activity of rheumatic diseases. <P> Patients and Methods: We performed a cross-sectional study, including patients with SID (rheumatoid arthritis (RA) and spondyloarthritis (SpA)). Disease activity was evaluated during the last check-up before COVID-19 and within the period of 6 months after the infection. Activity scores were assessed with Disease Activity Score (DAS28) for RA and Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Correlation and regression coefficients were used to evaluate associations among the variables. <P> Results and Discussion: Totally, thirty-two patients were included; twenty followed for RA and twelve for axial SpA. The mean disease duration of the underlying rheumatic disease was 10.2 years (2-30). RA was seropositive and erosive in 61% and 31%, respectively. Seventeen patients were on csDMARDs: 14 were on Methotrexate and three patients were on Salazopyrine. Ten patients (31%) were treated with bDMARDs; Tumor necrosis factor (TNF)-alpha inhibitors were used in eight cases. Rituximab and secukinumab were prescribed for one patient each. In 70%, COVID-19 was pauci-symptomatic. A severe form with a need for hospitalization was noted in 9%. Two patients were admitted to the intensive care unit (ICU). <P> Overall, treatment with DMARDs was interrupted in all cases: when COVID-19 symptoms began in 82% and when PCR was positive in 18%. Both RA and axial SpA were not active after a mean period of 6 months after COVID-19 infection (p = 0.818 and p = 0.626, respectively). <P> Conclusion: Although our patients interrupted their DMARDs, our study demonstrates that disease activity as assessed by ASDAS and DAS28 in SpA and RA remained unchanged after COVID-19.</P>]]></description> </item><item><title><![CDATA[Glucosamine Sulphate Potassium Chloride in the Management of
Osteoarthritis- Considering Emulgel Dosage Form: A Review]]></title><link>https://www.benthamscience.comarticle/124115</link><description><![CDATA[<p>Background: In addition to lifestyle, diet, environmental, and physiological factors, genetics also contributes to an increase in mitochondrial vulnerability. With depression, the hypothalamic, pituitary, and adrenal (HPA) axis are overactive, which is linked to higher CNS glucocorticoid levels. In recent years, topical drug delivery has been used on a priority basis compared to other drug delivery systems because of its specific site action and sustained release capacity. An emulsion gel is prepared by an emulsion incorporated into a gel by a gelling agent. Glucosamine Sulphate Potassium Chloride (GSPC) is used to treat osteoarthritis. It does this by increasing the production of proteoglycans, which can cause the cartilage to break down. <p> Objectives: The aim behind choosing the glucosamine sulphate potassium chloride for the management of Osteoarthritis (OA) is that it has many clinical investigations and has topical properties which are effective against osteoarthritis. <p> Methods: Osteoarthritis is a prevalent rheumatic musculoskeletal disorder. It is a pervasive disorder affecting people worldwide and can affect any joint, mainly the knees, hips, spine, and hand joints. The review is based on many studies extracted from Google Scholar, Google Patents, etc. Data from other sources were gathered to do further research on osteoarthritis. <p> Results: Extensive literature was studied about Glucosamine Sulphate Potassium Chloride. It has been shown that GSPC is effective against osteoarthritis, and also, some patents regarding GSPC have a therapeutic effect on making our joints healthy. <p> Conclusion: Topical formulations are widely used for better patient compliance, and emulgel is a good choice regarding viscosity and spreadability. GSPC is effective against osteoarthritis; many clinical studies have evidence of this.</p>]]></description> </item><item><title><![CDATA[Asymmetric Dimethylarginine as a Biomarker in Coronary Artery Disease]]></title><link>https://www.benthamscience.comarticle/128224</link><description><![CDATA[As atherosclerosis remains a leading cause of morbidity and mortality worldwide despite the advances in its medical and interventional management, the identification of markers associated with its incidence and prognosis constitutes an appealing prospect. In this regard, asymmetric dimethylarginine (ADMA), a well-studied endogenous endothelial nitric oxide synthase inhibitor, represents a core mediator of endothelial dysfunction in atherosclerotic diseases. Given the pathophysiologic background of this molecule, its importance in the most frequent atherosclerotic manifestation, coronary artery disease (CAD), has been extensively studied in the past decades. The available evidence suggests elevation of ADMA in the presence of common cardiovascular risk factors, namely diabetes mellitus, arterial hypertension, and hypertriglyceridemia, being related to endothelial dysfunction and incident major adverse cardiovascular events in these groups of patients. Moreover, ADMA is associated with CAD occurrence and severity, as well as its prognosis, especially in populations with renal impairment. Interestingly, even in the absence of obstructive CAD, increased ADMA may indicate coronary endothelial dysfunction and epicardial vasomotor dysfunction, which are prognostication markers for incident cardiovascular events. In the case of acute coronary syndromes, high ADMA levels signify an augmented risk of incomplete ST-segment elevation resolution and poorer prognosis. Abnormal ADMA elevations may indicate adverse outcomes following percutaneous or surgical coronary revascularization, such as in-stent restenosis, graft patency, and hard cardiovascular endpoints. Finally, since its association with inflammation is significant, chronic inflammatory conditions may present with coronary endothelial dysfunction and subclinical coronary atherosclerosis by means of increased coronary artery calcium, with augmented ADMA acting as a biomarker.]]></description> </item><item><title><![CDATA[Fibromyalgia in Spondyloarthritis: Prevalence and Effect on Disease
Activity and Treatment]]></title><link>https://www.benthamscience.comarticle/126104</link><description><![CDATA[<p>Background: Fibromyalgia may be associated to Spondyloarthritis with which it shares some common symptoms such as sleep disorders, fatigue and diffuse pain, leading to diagnostic and treatment dilemmas. <p> Objectives: We aimed to determine the prevalence of fibromyalgia in axial spondyloarthritis and to determine how fibromyalgia might influence the assessments of disease activity and how it might impact treatment. <p> Methods: An observational cross-sectional study was conducted. The study included 100 patients with axial spondyloarthritis according to the Assessment of SpondyloArthritis international Society criteria. Fibromyalgia was diagnosed based on the 2010 American College of Rheumatology criteria. Demographics, disease characteristics, activity parameters and treatment were compared between patients with and without fibromyalgia. Patients were recruited from the hospitalization unit and the outpatient clinic of rheumatology. <p> Results: The mean age of patients was 44.65 ± 13.13 years, with a sex ratio equal to 2. The prevalence of fibromyalgia was 20%. Fibromyalgia associated factors were advanced age and a late age at the onset of axial spondyloarthritis. Disease activity parameters such as global pain VAS, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI and BAS-G as well as MASES and BASMI were significantly higher in the presence of FM. Doses of paracetamol were significantly higher among FM+ patients. Also, treatment duration of the current anti-TNF alpha agent was significantly shorter among FM+ patients. <p> Conclusion: Our study showed that fibromyalgia was associated with axial spondyloarthritis in 20% of patients. Its presence was associated with higher disease activity parameters and negative impact on the treatment.</p>]]></description> </item><item><title><![CDATA[DFT and <i>In-silico</i> Investigations, along with <i>In-vitro</i> Antitumor and Antimicrobial
Assessments of Pharmacological Molecules]]></title><link>https://www.benthamscience.comarticle/126293</link><description><![CDATA[<p>Background: Molecules bearing an active methylene bridge are one of the most fruitful and remarkable precursors that have been incorporated into the synthetic strategy of an assortment of bioactive compounds. <p> Objective: The reactive methylene derivatives have been endowed with multiple reactions, which target biological and medicinal applications and result from their structural diversity and discrete reactivity. <p> Methods: The present report endeavors to synthesize, characterize, and in-vitro evaluate several novel propanoic acids, coumarin, and pyrazole derivatives as antimicrobial and antiproliferative agents. The in-silico molecular docking, physicochemical, pharmacokinetic/ADMET, bioactivity, and drug-likeness predictions were conducted for all the synthesized compounds. <p> Results: The highest docking score is -9.9 and -8.3 kcal/mol, respectively, for compound 9 (azocoumarin) and 13 (acrylic acid derivative) with the target proteins E. coli topoisomerase II, DNA gyrase subunit B and PI3K p110α domain, respectively. Moreover, this study predicts the synthesized molecules that may inhibit the novel COVID-19, obtained through virtual screenings only, where compounds 9, 13, 14, 17, and 19 came to the limelight with good docking scores i.e., more than -8 Kcal/mol. Safety profiling of the most potent compound 9 was utilized against normal cell lines and the hemolytic effect on RBCs. <p> Conclusion: The in-silico ADMET studies of the synthesized compounds revealed moderate to good -likeness, high gastro intestinal (GI) absorption, and inhibiting the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density functional theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gaps, dipolemoment, andmolecular electrostatic potential. Such parameters, along with the physicochemical parameters, could be a good tool to confirm biological activity.</p>]]></description> </item><item><title><![CDATA[<i>Citrus</i> Flavonoids and Autoimmune Diseases: A Systematic Review of
Clinical Studies]]></title><link>https://www.benthamscience.comarticle/124884</link><description><![CDATA[<p>Background: Autoimmune diseases are chronic disorders in which the immune system does not recognize and attacks one self’s healthy components. In this context, although natural remedies might represent a promising therapeutic strategy, evidence regarding Citrus flavonoids is still controversial. <p> Objective: To summarize and critically discuss the clinical evidence on the effects of Citrus flavonoids on managing autoimmune diseases. <p> Method: A systematic review of articles has been carried out independently by two authors using MEDLINE, Scopus and ISI Web of Science databases. Search terms comprised keywords related to Citrus flavonoids and autoimmune diseases. The last search was performed on the 16th of March, 2021. No language restrictions were applied. Systematic review and study selection were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Before starting the review, the authors defined the types of articles to be included. Three reviewers independently carried out the extraction of papers. <p> Results: Ten clinical studies fulfilled the eligibility criteria and were included in the final review. <p> Conclusion: The studies discussed in this review are heterogeneous. Indeed, some studies suggest using Citrus flavonoids in the frame of autoimmune disorders, whereas others discourage it. Hence, this systematic review highlights the need for further large-scale clinical studies to define the exact role of Citrus flavonoids in managing autoimmune diseases (PROSPERO number CRD42021234903).</p>]]></description> </item><item><title><![CDATA[Nutraceuticals in the Treatment of Inflammatory Bowel Disease: How
the Panorama has Changed in the Last Decade?]]></title><link>https://www.benthamscience.comarticle/123004</link><description><![CDATA[<p>Background: Inflammatory bowel diseases (IBD), mainly Ulcerative colitis (UC) and Crohn’s disease (CD), are recurrent idiopathic non-infectious chronic diseases widely diffused worldwide and characterized by moderate to severe mucosal damage. <p> Objective: This study aims to review the literature of the last 10 years to photograph preclinical and clinical data on the use of nutraceuticals in the prevention and treatment, combined with the conventional drugs, of IBD. <p> Method: PubMed, MEDLINE, Embase, Web of Science, and ClinicalTrials.gov were used to search for the most recent publications on in vitro, in vivo, and clinical evidence on IBD and nutraceuticals, which were then assessed based on the originality and scientific rigor of the studies. <p> Results: In the last decade, the interest in new healthy or therapeutic complementary or alternative approaches to conventional drugs in IBD has grown inexorably, as well as the incidence of these pathologies and the knowledge of their etiopathogenesis. In this context, a growing development of new nutraceutical products with a consequent increase in pre-clinical studies has been observed. However, this panorama does not yet translate into adequate clinical studies that can effectively endorse what was observed in pre-clinical studies; many of them are mostly aimed at resolving diseases related to IBD rather than IBD itself. <p> Conclusion: Despite the promising pre-clinical data about nutraceuticals and IBD, we are still very far from being able to postulate an adequate nutraceutical treatment of these pathologies and further studies are necessary to support this hypothesis.</p>]]></description> </item><item><title><![CDATA[Subcategories of Fibromyalgia - A New Concept]]></title><link>https://www.benthamscience.comarticle/121145</link><description><![CDATA[Fibromyalgia has previously been categorized as primary, secondary, and juvenile fibromyalgia. However, these definitions do not adequately explain the etiopathology of disease, nor do they help direct new specific therapies. Herein, we review the previously known categorizations of fibromyalgia. Based on common patient characteristics and previously studied pathophysiologies, we propose new subcategorizations of fibromyalgia that we have self-narrated, including hormonal fibromyalgia, neuroendocrine fibromyalgia, psychologic fibromyalgia, inflammatory fibromyalgia, and lastly neuropathic fibromyalgia. To verify, add to, and fully describe these selfnarrated categories of fibromyalgia that we have proposed, future research needs to be done.]]></description> </item><item><title><![CDATA[Interleukin-1 in Coronary Artery Disease]]></title><link>https://www.benthamscience.comarticle/127032</link><description><![CDATA[Cardiovascular disease is the leading cause of mortality worldwide. Inflammation has long been established as a key component in the pathophysiology of coronary artery disease. The interleukin-1 family consists of 11 members that regulate the inflammatory response through both pro- and anti-inflammatory properties with the Nod-like receptor (NLR) family pyrin domain containing 3 inflammasome having a pivotal role in the process of converting interleukin-1 beta and interleukin- 18, two key inflammatory mediators, into their mature forms. Interleukin-1 affects various cell types that participate in the pathogenesis of atherosclerosis as it enhances the expression of leukocyte adhesion molecules on the surface of endothelial cells and augments the permeability of the endothelial cell barrier, attracting monocytes and macrophages into the vessel wall and aids the migration of smooth muscle cells toward atheroma. It also enhances the aggregation of low-density lipoprotein particles in endothelium and smooth muscle cells and exhibits procoagulant activity by inducing synthesis, cell-surface expression and release of tissue factor in endothelial cells, promoting platelet adhesion. The value of interleukin-1 as a diagnostic biomarker is currently limited, but interleukin-1 beta, interleukin-18 and interleukin-37 have shown promising data regarding their prognostic value in coronary artery disease. Importantly, target anti-inflammatory treatments have shown promising results regarding atherosclerosis progression and cardiovascular events. In this review article, we focus on the immense role of interleukin-1 in atherosclerosis progression, inflammation cascade and in the clinical application of target anti-inflammatory treatments.]]></description> </item><item><title><![CDATA[Matrix Metalloproteinases; A Biomarker of Disease Activity and Prognosis
in Spondyloarthritis: A Narrative Review]]></title><link>https://www.benthamscience.comarticle/120156</link><description><![CDATA[<p>Background: Matrix metalloproteinases, as components of the proteolytic system, are deemed to be implicated in the pathogenesis and progression of several rheumatic diseases. Their role in spondyloarthritis has been investigated by several studies. <p> Objective: This article aims to review and summarize the current knowledge related to metalloproteinases in patients with spondyloarthritis. <p> Methods: To examine the association between matrix metalloproteinases and spondyloarthritis, we conducted a narrative review using a literature search in SCOPUS for English-language sources. The search included studies published from the database inception to December 2020. <p> Results: A total number of 74 articles were included. It was found that levels of matrix metalloproteinases 3 were higher in radiographic axial spondyloarthritis patients and seemed to play a role in the progression of joint damage. The levels of matrix metalloproteinases 1, 2, and 9 were upregulated in psoriatic arthritis patients compared to psoriasis and could identify psoriasis patients who would develop rheumatic manifestations. The levels of matrix metalloproteinases correlated significantly with disease activity in ankylosing spondylitis and decreased upon treatment with Tumor Necrosis Factor inhibitors (TNFi). <p> Conclusion: Excessive matrix metalloproteinases activity is associated with articular destruction. Their levels can reflect disease activity, structural damage, and response to TNFi in patients with spondyloarthritis. Nevertheless, further studies are needed to confirm these results.</p>]]></description> </item><item><title><![CDATA[Satisfaction with Social Roles and Physical Function in Immune-mediated
Inflammatory Diseases: A Cross-Sectional Study]]></title><link>https://www.benthamscience.comarticle/124098</link><description><![CDATA[<p>Background: Although mood disorders have been well characterized by immunemediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. <p> Objective: The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteristics. <p> Methods: Physical function and social role satisfaction were evaluated through the Patientreported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. <p> Results: Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p<0.001), while patients with inflammatory arthritis reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity, and occupation were positively associated with physical function and social role satisfaction (p<0.001; p=0.001; p<0.001; p=0.001 and p<0.001; p=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002) and biological treatment and ESR with social roles satisfaction (p<0.001; p=0.043; respectively). In the multivariable regression, gender was found to be associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction with social roles (p<0.001) and steroids for physical function (p=0.021), and social roles satisfaction (p=0.018). <p> Conclusion: Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patientreported outcomes should be considered in clinical management to define patients’ real needs.</p>]]></description> </item><item><title><![CDATA[Natural Inhibitors against Potential Targets of Cyclooxygenase, Lipoxygenase
and Leukotrienes]]></title><link>https://www.benthamscience.comarticle/117998</link><description><![CDATA[<p>Background: Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes catalyze the production of pain mediators like Prostaglandins (PGs) and Leukotrienes (LTs), respectively from arachidonic acid. <p> Introduction: The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and Cardiovascular Syndromes (CVS). Many synthetic Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc. <p> Methods: The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plantbased vs synthetic inhibitors. <p> Results: These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy. <p> Conclusion: Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.</p>]]></description> </item><item><title><![CDATA[Unknown Extra-Articular Manifestation of Spondyloarthritis: What
About Retroperitoneal Fibrosis? A Case Based Literature Review]]></title><link>https://www.benthamscience.comarticle/121850</link><description><![CDATA[<p>Introduction: Retroperitoneal fibrosis (RPF) is a rare disease characterized by fibroinflammatory tissue proliferation in the retroperitoneum. It results in a chronic inflammatory and fibrosis condition, possibly leading to compression of the retroperitoneal structures, especially to encasement of the ureters and the inferior vena cava. It may have an idiopathic or a secondary origin. Spondyloarthritis (SpA) is one of the rare conditions described among the secondary forms. <p> Case Presentation: Herein, we report a new case of RPF in a patient with AS presented with acute abdominal pain radiating to the lumbar region and the left testicle. On clinical examination, we found a mild stiffness of the lumbar spine and a decrease in chest expansion. Sacroiliac joint pain was also found. The rest of the physical examination was normal. Laboratory tests showed inflammation with increased C-reactive protein (130 mg/l) and creatinine (112 micromol/l) levels. The computed tomography scan revealed a soft tissue density mass located around the sub-renal aorta. Diagnosis of idiopathic RPF associated with AS was retained. The patient was treated with a daily dosage of 1 mg/kg of oral glucocorticoid with a good outcome. <p> Conclusion: RPF is a rare condition that can be either idiopathic or secondary. Its association with spondyloarthritis, mainly in its ankylosing spondylitis form, seems to be more than anectodal. Treatment may involve medical therapy and/or surgical management. <p> Key Message: In the presence of back pain, fatigue, weight loss, and low grade fever in spondyloarthritis patients, physicians should screen for retroperitoneal fibrosis as it could be a possible cause.]]></description> </item><item><title><![CDATA[Rare Clinical Case of Cryopyrin-associated Periodic Syndrome Presented
with Ankylosing Spondylitis: A Case Report]]></title><link>https://www.benthamscience.comarticle/118856</link><description><![CDATA[<p>Background: Cryopyrin-Associated Periodic Syndrome (CAPS) is a variety of clinical variants of autoinflammatory diseases. The pathology is based on a mutation in the NLRP3 gene encoding the cryopyrin protein, which leads to the uncontrolled production of interleukin-1&#946;. Particular attention should be paid to the rarity of this disease and the lack of clinical knowledge about it in therapeutic and rheumatological practice, which leads to an erroneous diagnosis and the appointment of ineffective treatment for a long time, leading to the progression of the disease and disability of the patient. <p> Case Presentation: This article describes a clinical case of this disease. The first manifestations of the disease in a woman appeared from the age of 2 years, in the form of a rash and fever. Since school age, there have been signs of arthritis. By the age of 24, sensorineural hearing loss and pain in the spine were evident. The disease occurred under the clinical manifestations of spondyloarthritis. Its treatment with anti-inflammatory therapy did not give a stable result. <p> Conclusion: From the analysis, we can conclude that patient M. from early childhood suffers from a severe Neonatal-onset Multisystem Inflammatory Disease of a genetic nature. For a long time, the patient was diagnosed with ankylosing spondylitis, and appropriate treatment was carried out without significant success. The correct diagnosis of CAPS was made only in 2018. This patient has conditions of both CAPS and AS together, which is a very rare association in rheumatological practice. The only treatment method that could stop the manifestations of the disease and prevent life-threatening kidney damage (amyloidosis) is the use of genetically engineered biological drugs, i.e., IL-1&#946; inhibitors. The only drug of this group registered in Russia is canakinumab (Ilaris®). From the moment of diagnosis to the present day, the patient is treated with the genetically engineered drug canakinumab (Ilaris®) at a dose of 150 mg once every 8 weeks. 6 months after taking the drug, the patient went into complete clinical and laboratory remission.]]></description> </item><item><title><![CDATA[Formulation and Evaluation of Naproxen Sodium Loaded Invasomes for
Topical Delivery]]></title><link>https://www.benthamscience.comarticle/123511</link><description><![CDATA[<p>Introduction: Naproxen sodium is a non-steroidal anti-inflammatory agent used in the treatment of rheumatoid arthritis and ankylosing spondylitis to relieve pain and inflammation. It mainly acts by inhibiting COX1 and COX2 receptors. By inhibiting the COX1 receptor, it causes severe gastric bleeding and peptic ulcer, and by inhibiting the COX2 receptor, it causes cardiovascular side effects. In order to avoid the adverse effects of naproxen, there is a need to develop a novel drug delivery system. So that invasomes, because of their vesicular structure, are capable of penetrating more into the systemic circulation and will be acting locally and systemically. <p> Methods: In this study, attempts have been made to prepare and characterize naproxen sodium loaded invasomes. Naproxen sodium loaded invasomes were prepared by thin film hydration technique using soya lecithin as lipid, span60 as surfactant, limonene as terpene and methanol, ethanol and chloroform as organic solvents. A total of twelve formulations (INV1-INV12) of invasomes were prepared, in which four formulations were prepared by varying drug to surfactant ratio and eight formulations were prepared by varying drug to lipid ratio. <p> Results and Discussions: All the formulations were evaluated for drug content, entrapment efficiency, particle size, zeta potential, and invitro drug release. Among the twelve formulations of invasomes, the INV2 formulation (1:1) ratio containing 40mg drug and 40mg surfactant (span60) was found to be the best formulation with a drug content of 96.62%, entrapment efficiency of 90.9%, zeta potential of -68.5mV, mean particle diameter of 572.4 nm, and invitro drug release of 91.6% in a time period of 12 hrs and followed the zero order kinetics with non fickian diffusion mechanism. <p> Conclusion: In this present study, naproxen sodium loaded invasomes were successfully prepared and evaluated.</p>]]></description> </item><item><title><![CDATA[A Systematic Approach to Diagnosing Arthritis Based on Radiological
Imaging]]></title><link>https://www.benthamscience.comarticle/122986</link><description><![CDATA[Radiology plays a key role in the diagnosis of arthritis. We herein suggest an algorithmic approach to diagnosing arthritis. First, the number of joint involvements is reviewed. Monoarticular arthritis includes septic arthritis, pigmented villonodular synovitis, and synovial chondromatosis. Second, polyarticular arthritis can be categorized by its characteristics: erosive, productive, and mixed. Erosive disease includes rheumatoid arthritis, hemophilia, and amyloidosis, while productive disease includes osteoarthritis and hemochromatosis. Third, mixed diseases are subcategorized by symmetricity. Ankylosing spondylitis and inflammatory bowel disease related arthritis affect joints symmetrically, while psoriatic arthritis, reactive arthritis, and crystalline arthropathy are asymmetric. Adjacent soft tissue density, periostitis, and bone density are ancillary findings that can be used as additional differential diagnostic clues. The final step in identifying the type of arthritis is to check whether the location is a site frequently affected by one particular disease over another. This systematic approach would be helpful for radiologists in diagnosing arthritis.]]></description> </item><item><title><![CDATA[COVID-19 Mortality in Patients with Rheumatic Diseases: A Real
Concern]]></title><link>https://www.benthamscience.comarticle/122492</link><description><![CDATA[<p>Background: Coronavirus disease 2019 (COVID 19) is a worldwide pandemic that has devastated the world in a way that has not been witnessed since the Spanish Flu in 1918. In this study, we aim to investigate the outcomes of patients with rheumatic diseases infected with COVID-19 in Oman. <p> Methods: A multi-center retrospective cohort study included patients with underlying rheumatological conditions and COVID-19 infection. Data were collected through the electronic record system and by interviewing the patients through a standard questionnaire. <p> Results: 113 patients with different rheumatic diseases were included with the following rheumatological diagnoses: rheumatoid arthritis (40.7%), systemic lupus erythematosus (23.1%), psoriatic arthritis (8%), Behcet&#039;s disease (7%), ankylosing spondylitis (6.2%), other vasculitides, including Kawasaki disease (4.4%), and other diagnoses (10.6%). The mean (SD) age of patients was 43 (14) years, and 82.3% were female. The diagnosis of COVID-19 was confirmed by PCR test in 84.1% of the patients. <p> The most common symptoms at the time of presentation were fever (86%), cough (81%), headache (65%), and myalgia (60%). Hospitalization due to COVID-19 infection was reported in 24.1% of the patients, and 52.2% of these patients had received some form of treatment. <p> In this cohort, the intake of immunosuppressive and immunomodulating medications was reported in 91.1% of the patients. During the COVID-19 infection, 68% of the patients continued taking their medications. Comorbidities were present in 39.8% of the patients. Pregnancy was reported in 2% of the patients. The 30 days mortality rate was found to be 3.5%. Diabetes, obesity, and interstitial lung diseases (ILD) were the strongest risk factor for mortality (p-value 0.000, 0.000, and 0.001, respectively). Rituximab was given in 3.8% of the patients, and it was significantly associated with increased mortality among the patients (p-value <0.001). <p> Conclusion: COVID-19 infection in patients with rheumatic diseases have an increased mortality rate in comparison to the general population, with diabetes, morbid obesity, chronic kidney diseases, interstitial lung disease, cardiovascular disease, obstructive lung disease, and liver diseases as comorbidities being the most severe risk factors associated with death. Greater care should be provided to this population, including the prompt need for vaccination.</p>]]></description> </item><item><title><![CDATA[Impact of Lean and Fat Mass on Disease Activity and Function in Spondyloarthritis]]></title><link>https://www.benthamscience.comarticle/122238</link><description><![CDATA[<p>Background and Aims: Changes in body mass composition, such as reduced lean and fat mass, can occur in a patient with rheumatic diseases. However, data about body composition in spondyloarthritis (SpA) showed conflicting results. The aim of the present study was to assess by DXA the distribution of lean and fat mass in SpA patients compared to healthy controls and to investigate the association between body mass composition and disease characteristics. <p> Methods: We conducted a cross-sectional case-control study including 50 SpA patients and 50 controls. Sociodemographic data, as well as disease characteristics, were assessed. Body composition measurements and biochemical and inflammatory serum markers were evaluated. Radiographic data (Bath Ankylosing Radiologic Index and the modified Stroke Ankylosing Spondylitis Spine Score) was also recorded. <p> Results: No statistically significant correlation was found between the two groups regarding bone mineral density and body mass distribution. However, a lower weight was observed in the study group compared to the control group (p = 0.043). Male gender and younger age were associated with a higher lean mass (p = 0.05). C-reactive protein (CRP) level was positively correlated with lean mass (r = 0.38, p = 0.023). Similarly, BASFI was higher in patients with lower fat mass (r = -0.42, p = 0.024). A longer duration of NSAIDs intake was associated with a lower lean mass and a higher fat mass. However, no correlations were found between body mass composition and BASRI mSASSS scores as well as bone mineral density and calcium intake. <p> Conclusion: Our findings suggest that younger age, male gender, and axial phenotype were associated with higher lean mass.</p>]]></description> </item><item><title><![CDATA[Cryofibrinogenemia: What Rheumatologists Should Know]]></title><link>https://www.benthamscience.comarticle/121873</link><description><![CDATA[Cryofibrinogenemia refers to the presence of cryofibrinogen in plasma. This protein has the property of precipitating at lower temperatures. Cryofibrinogenemia is a rare disorder, clinically characterized by skin lesions, such as ulcers, necrosis, livedo reticularis, arthralgia, thrombosis, and limb ischemia. These features are most often observed in rheumatological practice and consist of differential diagnoses of antiphospholipid syndrome, primary vasculitis, thrombotic thrombocytopenic purpura, and cryoglobulinemia. Classical histopathological findings include the presence of thrombi within the lumen of blood vessels of the skin without vasculitis. To date, there are no validated classification criteria. Management includes corticosteroids, immunosuppressive therapy, anticoagulants, and fibrinolytic agents. This narrative review aims to make physicians, particularly rheumatologists, aware of the existence of this underdiagnosed condition. There are no epidemiological studies evaluating the prevalence of cryofibrinogenemia in different rheumatological disorders. Studies are also required to investigate if certain features of rheumatological diseases are related to the presence of cryofibrinogenemia.]]></description> </item><item><title><![CDATA[Which Metrological Index, the BASMI or EDASMI, is Best Correlated
with Disease-Related Parameters in Spondylarthritis Patients?]]></title><link>https://www.benthamscience.comarticle/121211</link><description><![CDATA[<p>Objective: This study aimed at comparing the Edmonton Ankylosing Spondylitis Metrology Index (EDASMI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) to determine which of the two is best correlated with disease-related parameters in axial spondyloarthritis (axSpA) patients. <p> Methods: A cross-sectional study was carried out involving 86 patients with radiographic axSpA. Sociodemographic data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire were applied. Spinal mobility was assessed by two indices: the BASMI and the EDASMI. Structural damage of the spine was also evaluated by two indices: the Bath Ankylosing Spondylitis Radiology Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). <p> Results: Eighty-six patients with an average age of 43.21 ± 11.43 years (20-79) were included. Impaired spinal mobility, which corresponds to higher BASMI scores, was correlated with prolonged disease duration (p < 0.01, r = 0.310), higher ASDAS-CRP (p < 0.001, r = 0.386), severe functional disability on the BASFI (p < 0.01, r = 0.505) and poorer quality of life according to the ASQoL (p < 0.01, r = 0.369). However, the EDASMI score did not correlate with any disease parameter. The BASMI was correlated with the total BASRI (p < 0.01, r = 0.634) and mSASSS (p < 0.01, r = 0.388). Unlike the BASMI, the EDASMI was neither correlated with the BASRI (p = 0.520, r = 0.245) nor the mSASSS (p = 0.252, r = -0.120). <p> Conclusion: Our results indicate that among the studied metrological indices, the BASMI is more contributory since it is correlated with clinical disease parameters and structural damage, unlike the EDASMI.</p>]]></description> </item><item><title><![CDATA[Interleukin 6 Concentration in Synovial Fluid of Patients with Inflammatory
and Degenerative Arthritis]]></title><link>https://www.benthamscience.comarticle/120512</link><description><![CDATA[<p>Aim: The present study aims to compare interleukin 6 concentration in synovial fluid in patients with known types of arthritis. <p> Background: Persistent synovitis without known markers, such as Rheumatoid Factor (RF), Anti- Citrullinated Protein Antibodies (ACPA), and genetic markers as HLA-B27, is not uncommon. It is valuable to determine the presence of chronic inflammation and put it in correlation with agerelated changes, which are especially relevant for middle-aged patients with mono- or oligoarthritis, when the dilemma to start disease-modifying drugs for inflammatory disease often is present. Interleukin 6 (IL-6) plays a significant role in chronic inflammation. <p> Objectives: IL-6 concentration in synovial fluid reflects the presence and activity of joint inflammation. <p> Methods: Synovial fluid was obtained from 101 patients with chronic synovitis. IL-6 concentration was determined by the immunochemical luminescence method. <p> Results: The median IL-6 concentration in synovial fluid in patients with osteoarthritis (OA) was 138.0 pg/ml (interquartile range (IQR) 43.4 to 296.0); in patients with rheumatoid arthritis was 2516.5 pg/ml, (IQR 1136.0 to 25058.0); in reactive arthritis 2281.0 pg/ml (IQR 1392.0 to 8652.0); psoriatic arthritis 1964.0 pg/ml (IQR 754.0 to 7300.0); ankylosing spondylitis 2776.0 pg/ml (IQR 514.7, 3944.0); in a group with negative RF, ACPA and HLA-B27 inflammatory arthritis 2163.0 pg/ml (IQR 822.0 to 7875.0). There is statistically significant difference of IL-6 concentration comparing OA and each inflammatory arthritis group, p<0.0001. <p> Conclusion: IL-6 detection in the synovial fluid is helpful in arthritis evaluation. The results show that an IL-6 level over 1000 pg/ml suggests the diagnosis of inflammatory arthritis.</p>]]></description> </item><item><title><![CDATA[Satisfaction and Adherence to Biological Treatment in Patients with Rheumatic
Diseases]]></title><link>https://www.benthamscience.comarticle/119782</link><description><![CDATA[<P>Background: Autoimmune inflammatory rheumatic diseases have long been treated by conventional disease-modifying anti-rheumatic drugs. Biological therapy is a new era in the treatment of rheumatic diseases, but satisfaction and adherence to it is still not well tested. <P> Aims: To assess the satisfaction and adherence to biological treatment among patients with autoimmune inflammatory rheumatic diseases. <P> Methods: A cross sectional study was conducted among 56 patients suffering from inflammatory rheumatic diseases using Morisky 8 questionnaire and Treatment Satisfaction Questionnaire for Medication (TSQM) over a period of one month. <P> Results: About 76.8 % of the patients had medium adherence and the underlying cause of missing doses was the unavailability of the drugs. The mean satisfaction with biological treatment was 62.7±6.9. Patients who did not receive formal education had significantly higher satisfaction with the biological treatment than others 64.94±5.01 at a P value 0.04 (<0.05). <P> Conclusion: Patients with inflammatory rheumatic diseases in our study showed medium adherence and satisfaction. Authorities in the medical field are providing great help to these patients in need of biological therapy, but ensuring the availability of all doses of the biological treatment regimen is still necessary. Patient, family and nurse education programs are also necessary to maximize adherence and satisfaction.</P>]]></description> </item><item><title><![CDATA[Tuberculosis Infection Under Anti-TNF Alpha Treatment]]></title><link>https://www.benthamscience.comarticle/118757</link><description><![CDATA[<p>Background: Anti-tumor necrosis factor-&#945; (TNF-&#945;) is a life-changing treatment leading to quality-of-life improvement. Nonetheless, this treatment is associated with a high risk of infection, especially tuberculosis. <p> Objective: Our study aimed to determine the frequency of active tuberculosis in our patients with chronic rheumatic disease and treated with TNF-&#945;. <p> Methods: We conducted a retrospective study including patients with Rheumatoid Arthritis and Spondylarthritis diagnosed according to ACR/EULAR 2009 criteria and ASAS 2010, respectively, and treated with biological agents for at least 6 months. We collected data regarding tuberculosis screening and the occurrence of active tuberculosis during follow-up. <p> Results: 82 patients were included (37 men and 45 women). The mean age was 42 ± 3.4 years. At inclusion, no patient had a medical history of tuberculosis. The diagnosis of latent tuberculosis infection was established in 17 patients (20.7%). Prophylactic treatment was prescribed in all these cases for three months. Two cases (2.4%) of active tuberculosis occurred under biologic (infliximab). It was two severe forms of tuberculosis. The first case had miliary tuberculosis associated with hepatic and peritoneal involvement. The second one had pleural tuberculosis. These two patients received anti-tuberculosis therapy, and the biological treatment was interrupted. Given the high disease activity, the anti-TNF-&#945; was restarted after 3 and 4 months. There was no recurrence of tuberculosis after 7 years of follow-up. <p> Conclusion: The use of TNF-&#945; blockers is associated with a risk of disseminated forms of tuberculosis. Tuberculosis screening, which is recommended before the biological onset, is also necessary under this treatment. Restarting the anti-TNF-&#945; after appropriate treatment of tuberculosis seemed to be safe.</p>]]></description> </item><item><title><![CDATA[Gait in Patients with Axial Spondyloarthritis: A Systematic Review of the
Literature]]></title><link>https://www.benthamscience.comarticle/118087</link><description><![CDATA[<p>Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton. axSpA includes radiographic (<i>i.e<i>., ankylosing spondylitis (AS)) and non-radiographic forms (nr-axSpA). Although recent studies have reported that patients with AS have impaired gait, axSpA’s consequences on gait remain unknown. The present review’s objectives were to identify: 1) how gait is assessed in patients with axSpA, and 2) what the gait characteristics are of patients with axSpA. <p> This systematic review’s protocol was registered in the Prospero database (CRD42020128509). Three databases were systematically searched using keywords related to axSpA and gait. Two independent reviewers selected the articles and extracted the data. <p> The search revealed two hundred titles and abstracts, and two articles were finally included in this review, comprising a total of 132 patients with axSpA. One of the included studies used the 6 m maximum gait velocity test (axSpA: 2.2 ± 0.5 m/s), and the other used the six-minute walk test (axSpA: 414 ± 106 m). Neither study involved a control group to compare gait. <p> Only two published studies assessed the gait performance of patients with axSpA using clinical tests. Furthermore, neither of them compared gait performance to healthy controls or differentiated gait between the AS and nr-axSpA forms of axSPA. The present literature review highlights the need for future research to learn more about how gait is impaired in different types of patients with axSpA.</p>]]></description> </item><item><title><![CDATA[A Systematic Review and Meta-analysis of Clinical Studies on Ankylosing
Spondylitis and Neutrophil to Lymphocyte Ratio]]></title><link>https://www.benthamscience.comarticle/118086</link><description><![CDATA[<p>Background: Neutrophil to lymphocyte ratio (NLR) is a marker for many inflammatory diseases. Ankylosing spondylitis (AS) is among these inflammatory diseases, and many studies have compared the NLR ratio between patients with AS and healthy controls. <p> Aim: This study aims to systematically review and analyze the available evidence about the significance of NLR values in AS. <p> Method: Based on Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, we searched Embase, Pubmed, ISI Web of Science, and Scopus databases from inception to August 2020 using (“Ankylosing spondyl* ” OR “Bechterew Disease” OR “Rheumatoid Spondylitis”) AND ((neutrophil* AND lymphocyte*) OR NLR) as key terms of the search strategy. Data selection and extraction were conducted separately by two authors. We appraised the included articles according to the Joanna Briggs checklist. Comprehensive Meta-analysis Version 2 was used for analysis and assessment of publication bias. I2 > 75% and p-value < 0.05 were considered significant. <p> Result: In total, 182 studies resulted from a search in all databases. Duplicate removal, title, abstract, and full-text screening yielded 12 related studies, with 11 included in the meta-analysis. Quality assessment was satisfying in all studies. Pooled difference in NLR means value between patients and controls was 0.38 (95% CI: 0.24-0.52, p-value <0.0001). An I2 of 51% and a Cochran Q test p-value of <0.05 indicated moderate heterogeneity; thus, subgroup analysis had no indication. Publication bias was not significant (Funnel plot with an Egger’s intercept of -0.07; p-value=0.95). <p> Conclusion: Significant higher amounts of NLR may be strongly indicative of underlying inflammation in AS.</p>]]></description> </item><item><title><![CDATA[The Role of Celecoxib as a Potential Inhibitor in the Treatment of
Inflammatory Diseases - A Review]]></title><link>https://www.benthamscience.comarticle/117863</link><description><![CDATA[This article aims at reviewing celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) predominantly has two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role related to homeostatic effects in renal and platelets, while the latter is mainly responsible for the induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and have no side effects. In this sense, celecoxib is the only potent, selective COX-2 inhibitor that is still commercially available (within the “coxib” family). Thus, celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for the COX-2 enzyme. This review provides inhibition highlights that should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs), which act as COX-2 inhibitors with lesser side effects on the human body.]]></description> </item><item><title><![CDATA[Transdermal Anti-inflammatory Delivery for Solid Lipid Nanoparticles of
Ketoprofen by Microwave-assisted Microemulsion]]></title><link>https://www.benthamscience.comarticle/120390</link><description><![CDATA[<p>Aims: To prepare solid lipid nanopaticles (SLNs) of Ketoprofen (KP) using microwave method. Ketoprofen (KP) is 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic property. The drug has a short half-life of 120 mins. It belongs to BCS Class II drug. Gastric irritation is a major limitation for delivery because of acidic nature of the drug. The development of solid lipid nanoparticles with its transdermal drug delivery was the aim of the present work. <p> Methods: Microwave-assisted microemulsion technique was used for the development of solid lipid nanoparticles. Stearic acid was used as lipid and tween 80 was used as a surfactant. By varying the type of lipid and input energy watt, batches were formulated. SLNs were evaluated for zeta potential, drug entrapment, particle size and in-vitro drug release. Crystallinity behaviour was determined by differential scanning calorimetry and powder X-ray diffraction. Anti-inflammatory activity was evaluated for batch M4 of SLNs. The gel was prepared for M4 batch. It was evaluated for viscosity, pH, drug content, in-vitro and ex-vivo diffusion study. <p> Results: SLNs were developed successfully. Based on the size, entrapment efficiency, stability and drug release, batch M4 was selected. SLNs showed 74.8% entrapment efficiency. Forty-fold improvement was observed in the solubility. The particle size was 682.9 nm and average size 1047 nm. PDI was 0.685 and zeta potential was -29.5 mV. M4 SLNs batch of gel showed burst release followed by a controlled release for 8 hrs in in-vitro drug release. <p> Conclusion: SLNs were successfully prepared by Microwave-assisted microemulsion technique. SLNs with anti-inflammatory activity were successfully developed with their transdermal delivery.</p>]]></description> </item><item><title><![CDATA[Amelioration of Cisplatin-induced Renal Inflammation by Recombinant Human Golimumab in Mice]]></title><link>https://www.benthamscience.comarticle/117242</link><description><![CDATA[Background: One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis, ulcerative colitis and ankylosing spondylitis. <p> Objective: Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity. <p> Method: Renal toxicity was caused by administration of single cisplatin injection at 22 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments. <p> Results: Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and β-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1β, MCP-1, ICAM-1, and TGF-β1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1β, ICAM-1, and TGF-β1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice. <p> Conclusion: The study’s results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.]]></description> </item><item><title><![CDATA[Emerging Role of Circular RNAs in Kidney Diseases in Nephrology]]></title><link>https://www.benthamscience.comarticle/117144</link><description><![CDATA[Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized. <P> Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis. <P> Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using keywords circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus. <P> Results: Studies of circRNAs in certain kidney diseases, such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage, and particular lupus nephritis address the function and pathogenesis of circRNAs. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring of the progression of kidney diseases. <P> Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology.]]></description> </item><item><title><![CDATA[TNF-induced Lupus. A Case-Based Review]]></title><link>https://www.benthamscience.comarticle/118648</link><description><![CDATA[Nowadays, tumor necrosis factor-alpha (TNFα) inhibitors have revolutionised the treatment of inflammatory arthritides by demonstrating efficacy with an acceptable toxicity profile. However, autoimmune phenomena and clinical entities have been reported ranging from an isolated presence of autoantibodies to full-blown autoimmune diseases, including drug-induced lupus (DIL). <P> Case Presentation: A 62-year-old woman with rheumatoid arthritis (RA) refractory to methotrexate and prednisone was treated with adalimumab (ADA). 4 months later, she presented acute cutaneous eruptions after sun exposure, positive ANA (1/640 fine speckled pattern), Ro (SSA) and anti- Smith (Sm) antibodies with no other clinical or laboratory abnormalities. The diagnosis of DIL was made, ADA was discontinued, and she was treated successfully with prednisone plus local calcineurin inhibitors. <P> Conclusion: Thus, we review the literature for cases of DIL development in patients treated with TNFα inhibitors. Rheumatologists should be aware of the possible adverse events and the requirement of careful clinical evaluation and monitoring.]]></description> </item><item><title><![CDATA[Evaluation of the Fibromyalgia and Related Risk Factors in Patients with Advanced Kidney Failure Undergoing Hemodialysis]]></title><link>https://www.benthamscience.comarticle/118527</link><description><![CDATA[Background: Fibromyalgia syndrome (FMS) is defined as widespread and persistent pain in the musculoskeletal system. There are limited reports regarding the prevalence of fibromyalgia syndrome in patients with advanced kidney failure undergoing regular hemodialysis. Therefore, this study aimed to evaluate the prevalence of fibromyalgia syndrome and its risk factors in a large proportion of patients under the hemodialysis condition. <P> Materials and Methods: In this cross-sectional study, 293 patients who were admitted to the hemodialysis ward were evaluated for fibromyalgia syndrome in an educational hospital. The questionnaire was designed according to symptom severity score (SS score) and widespread pain index (WPI) criteria. The correlation between FMS and various variables, including demographic, clinical, and biochemistry biomarkers, was also precisely calculated by logistic regression. Data were analyzed using SPSS v.17 statistics software. <P> Results: The results showed that, of 293 hemodialysis patients, 130 patients (44.4%) had fibromyalgia, the mean age of patients with and without fibromyalgia was 61.09 ± 15.36 and 53.49 ± 15.38 years old, respectively (P = 0.001). Moreover, there was a significant difference in terms of gender among patients with fibromyalgia syndrome (P = 0.001). To note, there was no significant relationship between the kidney failure etiopathogenesis, duration of dialysis, body mass index (BMI), Kt/v index, history of peritoneal dialysis, and laboratory parameters with fibromyalgia in hemodialysis patients (P > 0.05). However, our findings revealed that both age and gender could be considered as the predictor variables associated with fibromyalgia in patients undergoing hemodialysis. <P> Conclusion: Taken together, in this study, we found that age and gender would be the critical factors in terms of the fibromyalgia syndrome in patients undergoing hemodialysis.]]></description> </item><item><title><![CDATA[Associated Factors with the Severity of Hip Involvement in Spondyloarthritis and Efficacy of TNF α Inhibitors in these Patients]]></title><link>https://www.benthamscience.comarticle/118432</link><description><![CDATA[Introduction: Hip involvement in patients with spondyloarthritis is responsible for disability and functional impairment. Its treatment is not codified. Our study aimed to determine the associated factors with moderate and severe hip involvement in spondyloarthritis patients. It also aimed to assess the efficacy of tumour necrosis factor inhibitors (TNFi) on hip disease. <P> Methods: We conducted a cross-sectional study, including 44 spondyloarthritis patients with hip involvement. Hip involvement was diagnosed based on radiographic findings. We assessed the following parameters: Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), patient global assessment (PGA), and Lequesne index. We compared these parameters and the mean radiographic joint space width between the time of the study to those right before the use of TNFi. <P> Results: Hip involvement was bilateral in 31 patients. The mean age was 44.56±12.21 years. There were 29 men. Severe and moderate involvement (BASRI-hip>3) was reported in 21 hips from 75 affected. These patients were older and had longer diagnosis delays than patients with BASRI- hip<3. They had a higher body mass index and more limited spine mobility (BASMI). Functional hip impairment assessed by the Lequesne index was higher in these patients. TNFi prescribed in 23 patients with hip involvement, led to an improvement in the Lequesne index (12.75 vs 7.5, p: 0.001) and PGA (7 vs 2, p: 0.001). However, the mean joint space width remained unchanged (3.8 vs 3.7mm, p: 0.532). <P> Conclusion: Our study showed that higher body mass and Lequesne indexes are associated with moderate and severe hip involvement. TNFi may improve both the Lequesne index and PGA and stabilize the radiological findings.]]></description> </item><item><title><![CDATA[Association of Large Vessel Aneurysm/Pseudo-Aneurysm/Aortitis and Deep Vein Thrombosis in Patients with Behçet’s Disease: A Case Report]]></title><link>https://www.benthamscience.comarticle/118068</link><description><![CDATA[Background: Behçet’s disease (BD) is a complex vasculitis with some vascular manifestations including venous thrombosis, arterial thrombosis/aneurysm/pseudoaneurysm, and co-associated venous thrombosis and arterial lesions. We present two patients with Behçet’s disease came with progressive both arterial and venous involvement. <P> Case Presentation: The first patient was a young man with recurrent oral aphthosis and skin folliculitis and referred with complaint of new abdominal pain and 2 months severe headache. He had not referred to a physician due to COVID-19 pandemic until that time. In addition, he gradually developed a lower extremity edema and eventually was diagnosed with BD complicated with brain sagittal sinus vein thrombosis, abdominal aortic aneurysms and aortitis and deep vein thrombosis (DVT) of femoral vein. The second patient was a young woman with previous history of uveitis, DVT and recurrent oral and genital aphthosis presented with a large inguinal mass due to large iliac artery pseudoaneurysm impending to rupture, and after the operation, due to poor follow-up, developed a new femoral DVT. <P> Conclusion: It seems the same inflammatory process is responsible for arterial and venous involvement in patients with BD, so it should be considered that involvement in one side (venous/arterial) can be a risk factor for the other side (venous/arterial) and early immunosuppressive treatment should always be considered to improve the prognosis.]]></description> </item><item><title><![CDATA[Effect of Different Carriers on In Vitro and In Vivo Drug Release Behavior of Aceclofenac Proniosomes]]></title><link>https://www.benthamscience.comarticle/114380</link><description><![CDATA[<P>Background: Improved bioavailability of Aceclofenac (ACE) may be achieved through proniosomes, which are considered as one of the most effective drug delivery systems and are expected to represent a valuable approach for the development of better oral dosage form as compared to the existing product. However, the carrier in this system plays a vital role in controlling the drug release and modulating drug dissolution. Accordingly, a comparative study on different carriers can give a clear idea about the selection of carriers to prepare ACE proniosomes. <P> Objective: This study aims to evaluate the role of maltodextrin, glucose, and mannitol as carriers for in vitro and in vivo performance of Aceclofenac (ACE) proniosomes. <P> Methods: Three formulations of proniosomes were prepared by the slurry method using the 100 mg ACE, 500 mg span 60, 250 mg cholesterol with 1300mg of different carriers, i.e., glucose (FN1), maltodextrin (FN2), and mannitol (FN3). In vitro drug release studies were conducted by the USP paddle method, while in vivo studies were performed in albino rats. Pure ACE was used as a reference in all the tests. Lastly, the results were analyzed using the High-Pressure Liquid Chromatography (HPLC) method, and data were evaluated using further kinetic and statistical tools. <P> Results: No significant differences (p > 0.05) in entrapment efficiency (%EE) of FN1, FN2, and FN3 (82 ± 0.5%, 84 ± 0.66%, and 84 ± 0.34% respectively) were observed and formulations were used for further in vitro and in vivo evaluations. During in vitro drug release studies, the dissolved drug was found to be 42% for the pure drug, while 70%, 17%, and 30% for FN1, FN2, and FN3, respectively, at 15 min. After 24 hrs, the pure drug showed a maximum of 50% release while 94%, 80%, and 79% drug release were observed after 24 hr for FN1, FN2, and FN3, respectively. The in vivo study conducted on albino rats showed a higher Cmax and AUC of FN1 and FN2 in comparison with the pure ACE. Moreover, the relative oral bioavailability of proniosomes with maltodextrin and glucose as carriers compared to the pure drug was 183% and 112%, respectively. Mannitol- based formulation exhibited low bioavailability (53.7%) that may be attributed to its osmotic behavior. <P> Conclusion: These findings confirm that a carrier plays a significant role in determining in vitro and in vivo performance of proniosomes and careful selection of carrier is an important aspect of proniosomes optimization.</P>]]></description> </item><item><title><![CDATA[Pharmacologic Activities of 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4-
triazines as a Privileged Scaffold in Drug Development]]></title><link>https://www.benthamscience.comarticle/114902</link><description><![CDATA[1, 2, 4-Triazine derivatives have received much attention due to their multifunctional nature, especially in diverse pharmacological properties as well as a key fragment in many drug candidates. Introduction of a vicinal 5, 6-diaryl/heteroaryl moiety on the 1, 2, 4-triazine ring has attracted plentiful attention in the field of medicinal chemistry. 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4- triazine is a prominent scaffold in many drug candidates, which has shown a wide range of pharmacological activities such as anti-diabetic, antifungal, anti-inflammatory, anticancer, anti-HIV, neuroprotective, anticonvulsant, anti-Alzheimer, anti-Parkinson, and antioxidant. In this review, we have discussed synthesis, various pharmacological activities of 5, 6-diaryl/heteroaryl-3-substituted-1, 2, 4- triazines, their structure-activity relationship (SAR), pharmacophoric elements, and their mechanism of action reported in the published articles during 2000-2019. Evaluation of compounds by PAINS filtering tool was accomplished and showed that this versatile structure could be considered as a privileged structure. Compilation of the biological data confirmed that position 3 of the 1,2,4-triazine is a key location to determine the affinity and selectivity of the 5,6-diaryl/heteroaryl-3-substituted-1, 2, 4- triazines towards different biologic targets. Specific geometrical and thermodynamic characters of this motif have prompted it as a frequent hitter.]]></description> </item><item><title><![CDATA[No Association of MicroRNA-146a rs2910164 Polymorphism and Risk of Primary Gout Development in Chinese Han Populations: A Case-control Study]]></title><link>https://www.benthamscience.comarticle/116847</link><description><![CDATA[<P>Background: Previous studies demonstrated that MicroRNA-146a (miR-146a) plays an important role in the regulation of autoinflammatory diseases including primary gout. The G/C polymorphism (rs2910164) in the precursor sequence of miR-146a caused its stem region to change from G: U to C: U,which can contribute to the susceptibility of human diseases. However, no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. <P> Objective: The purpose of this study was to analyze the association between the miR-146a rs2910164 genetic polymorphism and the susceptibility of the Chinese Han population to primary gout. <P> Methods: 1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5&#039;exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. <P> Results: After statistical analysis, no significant differences were observed between gout patients and healthy controls in genotype and allele frequency. <P> Conclusion: Our results indicate that there is no evidence for the involvement of the miR-146a rs2910164 polymorphisms in susceptibility to primary gout in the Chinese Han population.</P>]]></description> </item><item><title><![CDATA[Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences]]></title><link>https://www.benthamscience.comarticle/114765</link><description><![CDATA[<P>Objectives: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). <P> Methods: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. <P> Results: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), and mSASSS (p=0.003). ASDAS - CRP was the only significant predictor of hypovitaminosis D in AS patients. <P> Conclusion: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.</P>]]></description> </item><item><title><![CDATA[Correlations and Influence of TAP2 Genes Polymorphisms and Systemic Lupus Erythematosus Propensity]]></title><link>https://www.benthamscience.comarticle/114820</link><description><![CDATA[<P>Objectives: The present study was designed to evaluate the association of transporters associated with antigen processing (TAP2) polymorphisms TAP2-379Ile > Val (rs1800454), TAP2-665Thr > Ala (rs241447) and TAP2-565Ala > Thr (rs2228396) as a candidate gene with susceptibility to the Systemic Lupus Erythematosus (SLE). <P> Methods: To analyze these three polymorphic variants, 88 patients with SLE and 100 healthy controls from northeastern Iran were enrolled from May 2018 to July 2019. Genomic DNA polymorphisms were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Data were analyzed by SPSS software. <P> Results: In this cross-sectional study, there was a stratification between patients and controls. The distribution of the frequency of Ala73 (41.5%) allele at TAP2/665 and Ile 19 (10.8%) allele at TAP2/379 was higher in patients. Additionally, the Ala/Ala 13(14.8%) and Ala/Thr 49(55.7%) genotypes distributions at 665 positions were higher in SLE patients compared to the controls. Furthermore, frequencies of TAP2*H allele significantly increased in SLE patients 10(5.71%) (P=0.01). Frequency of TAP2*A allele in the control group was 120(60%) (p=0.06) due to the dominant genetic model. This allele has a protective effect against SLE. There was no relationship between TAP2*D, TAP2*E, TAP2*F and TAP2*G alleles with the outbreak of SLE. <P> Conclusion: Our data indicated that genetic variants in TAP2 gene may be associated with SLE disease. A correlation between Ala allele at TAP2/665 and Ile allele at TAP2/379 polymorphisms and pathogenesis of SLE was observed.</P>]]></description> </item><item><title><![CDATA[Extraction and Evaluation of Anti-inflammatory and Analgesic Activity of Mimosa rubicaulis in Swiss Albino Rats]]></title><link>https://www.benthamscience.comarticle/110569</link><description><![CDATA[Background: Pain and inflammation are major health problems. The adverse effect of synthetic drugs for the management of painful inflammatory conditions gives a strong motivation for researchers to develop newer drugs with lesser side effects. Mimosa rubicaulis has been traditionally used in rheumatism, fungal infection, wound, fever, etc. <p> Objective: The objective was to evaluate the anti-inflammatory and analgesic activity of ethanolic stem extract of M. rubicaulis in Swiss albino rats. <p> Methods: The stem of M. rubicaulis was collected, subjected to double maceration using ethanol as a solvent. Then, Swiss albino rats (n=72) were taken. An acute toxicity study was conducted using different doses of the plant extract. The anti-inflammatory activity (100 mg/kg, 250 mg/kg) was evaluated using the carrageenan-induced paw edema test, while, analgesic activity (100 mg/kg, 250 mg/kg) was evaluated using a hot plate and tail immersion method. The result was analyzed using a one-way analysis of variance and post hoc analysis with the Tukey test. <p> Results: The acute toxicity study showed that the plant is safe for use in an animal model. The extract showed anti-inflammatory activity by a reduction in paw edema volume by 25% and 48%. Similarly, analgesic activity was shown by an increase in latency of paw licking and tail withdrawal by 41%, and 56% (hot plate method) and 39% and 54% (Tail immersion method), p<0.05. <p> Conclusion: It can be concluded that the ethanolic extract of Mimosa rubicaulis is safe and possesses both anti-inflammatory and analgesic activity.]]></description> </item><item><title><![CDATA[Potential Role of Bioactive Lipids in Rheumatoid Arthritis]]></title><link>https://www.benthamscience.comarticle/115786</link><description><![CDATA[Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that involves a pathological inflammatory response against articular cartilage in multiple joints throughout the body. It is a complex disorder associated with comorbidities such as depression, lymphoma, osteoporosis, and cardiovascular disease (CVD), which significantly deteriorate patients’ quality of life and prognosis. This has ignited a large initiative to elucidate the physiopathology of RA, aiming to identify new therapeutic targets and approaches in its multidisciplinary management. Recently, various lipid bioactive products have been proposed to have an essential role in this process, including eicosanoids, specialized pro-resolving mediators, phospholipids/sphingolipids, and endocannabinoids. Dietary interventions using omega-3 polyunsaturated fatty acids or treatment with synthetic endocannabinoid agonists have been shown to significantly ameliorate RA symptoms. Indeed, the modulation of lipid metabolism may be crucial in the pathophysiology and treatment of autoimmune diseases.]]></description> </item><item><title><![CDATA[Immunosuppressant Drugs and Covid-19: Associated Risks, Drug-Drug Interactions and Contraindications]]></title><link>https://www.benthamscience.comarticle/115901</link><description><![CDATA[Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclosporine, and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase mortality and morbidity, as a weakened immune system can lead to a longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and their associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organization), U.S FDA (Food and Drug Administration), and other accredited global health organizations. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications, and drug-drug interactions. Our study will help government partners and international health organizations to understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised, and organ transplant patients will help lower the mortality and morbidity associated with the disease amid the COVID-19 pandemic.]]></description> </item><item><title><![CDATA[Ankylosing Spondylitis and Risk of Cardiac Arrhythmia and Conduction Disorders: A Systematic Review and Meta-analysis]]></title><link>https://www.benthamscience.comarticle/115650</link><description><![CDATA[ Objective: The objective of this study isto assess the association between ankylosing spondylitis (AS) and risk of heart conduction disorders and arrhythmia. </p> Methods: PubMed, Embase, and Web of Science databases were systematically searched for observational studies that investigated the association between AS and risk of heart conduction disorders and arrhythmia with no language or date restrictions until September 16, 2019. We used randomand fixed-effects models to pool the results of the studies. Publication bias was assessed by Egger’s test. Subgroup analysis was carried out based on the study design. A p-value less than 0.05 was considered significant. Comprehensive Meta-Analysis (CMA) software was used to perform meta-analysis. </p> Results: After removing duplicates, we reviewed 135 articles. Finally, we included seven articles in our meta-analysis, of which four studies reported AV block and any conductive abnormality and three focused on atrial fibrillation and any arrhythmia. Based on our meta-analysis, an increased risk of atrial fibrillation (RR: 1.85, 95%CI: 1.15-2.98) and atrioventricular block (OR: 3.46, 95%- CI: 1.09-10.93) was found in AS subjects compared to the general population. In a subgroup analysis based on study design, we found a greater association between AS and atrioventricular block in cohort studies (RR: 5.14, 95%CI: 1.001-26.50) compared to cross-sectional ones. However, we did not find any association between AS and any arrhythmia (OR=3.36, 95% CI: 0.93-12.15), or conduction disorders (OR: 0.64, 95%CI: 0.38-1.06). No publication bias was found. </p> Conclusion: Our results support an association between AS and a higher risk of atrial fibrillation and atrioventricular block.]]></description> </item><item><title><![CDATA[Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments]]></title><link>https://www.benthamscience.comarticle/117664</link><description><![CDATA[<p>Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. </P><P> Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. </P><P> Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). </P><P> Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). </P><P> Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.</p>]]></description> </item><item><title><![CDATA[The Interplay of Disease Modifying Anti Rheumatic Drugs and Tuberculin Skin Test]]></title><link>https://www.benthamscience.comarticle/112910</link><description><![CDATA[<P>Objective: The study was conducted to determine whether synthetic Disease-Modifying Anti Rheumatic Drugs (DMARDs) suppress the latency of Tuberculosis (TB) infection in Rheumatoid Arthritis (RA) patients along with other variables. </P><P> Methods: This was done through Tuberculin Skin Test (TST) using purified protein derivative (PPD) in a cohort of RA patients. The TST was taken positive when induration post-PPD injection was ≥ 5mm and negative or anergic when it was < 5mm. We included 100 patients (N = 100). </P><P> Results: The prevalence of positive TST was 36%, while 64% presented a negative result. Negative TST was significantly associated with steroid usage (39.4%, 95% CI: 28.4%-51.4%). Anergic (TST negative) and non-anergic (TST positive) patients were separated into groups, and a new analysis was conducted with elaboration on DMARDs used. </P><P> Conclusion: The use of steroids was associated with TST negativity, The same is not true with use of methotrexate or other DMARDs. Thus TST should be interpreted with caution, especially before starting biologicals.</P>]]></description> </item><item><title><![CDATA[Osteogenic Differentiation Factors of Multipotent Mesenchymal Stromal Cells in the Current Understanding]]></title><link>https://www.benthamscience.comarticle/115223</link><description><![CDATA[<P>Background: Molecular genetic mechanisms, signaling pathways, conditions, factors, and markers of the osteogenic differentiation of mesenchymal stem cells (MSCs) are being actively studied and are among the most studied areas in the field of cellular technology. This attention is largely due to the mounting contradictions in the seemingly classical knowledge and the constant updating of results in the analyzed areas. In this regard, we focus on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. </P><P> Results: This review considers the importance of the sources of MSCs for the realization of their differentiation potential, molecular genetic factors and signaling pathways of MSC differentiation, the role of inflammatory cytokines and chemokines in osteogenesis, biomechanical signals, and the effect of conformational changes in the cellular cytoskeleton on MSC differentiation. </P><P> Conclusion: It is concluded that it is necessary to move from studies focused on the effects of local genes to those taking multiple measurements of the gene-regulatory profile and the biomolecules critical for the implementation of numerous, incompletely studied osteogenic factors of endogenous and exogenous origin. Among the cornerstones of future (epi)genetic studies, whether osteomodulatory effects are realized through specific signaling pathways and/or whether cross-signaling with known genes drives the osteogenic differentiation of MSCs remains to be determined.</P>]]></description> </item><item><title><![CDATA[Recent Advances in Psoriasis Therapy: Trends and Future Prospects]]></title><link>https://www.benthamscience.comarticle/113362</link><description><![CDATA[<p>Background: Psoriasis is a challenging skin disorder due to its chronicity, high rate of prevalence, disability, comorbidity and disfiguration. It is a multi-system disorder that includes joints and metabolic syndromes. Psoriasis is a condition of pathologic interaction among immune cells, biological signaling molecules and skin cells. Several contributing factors are responsible for the exacerbation and onset of psoriasis, i.e. genetic factors and environmental factors such as medications, infectious diseases and lifestyle. </P><P> Objectives: To study the new insights in the treatment of psoriasis and future prospects. </P><P> Methods: This review article gives an insight on the current concepts of psoriasis and deals with discussing the initiation and development of the diseases. We described the pathogenetic pathway for psoriasis. The article focuses on the treatment approaches for psoriasis that have arisen from the dissection of the inflammatory psoriatic pathways. </P><P> Results: We aimed to highlight the novel therapies and drugs used in the treatment of psoriasis, including food and drug administration (FDA) approved drugs and drugs under clinical trials. The treatment can be initiated for mild to the moderate diseased condition employing vitamin D3 analogues, corticosteroids and a combination of products as first-line therapy. </P><P> Conclusion: Psoriasis can be managed by a proper understanding of the immune function. We have also discussed medicinal herbs used for psoriasis based on their ethnopharmacological knowledge and reported work of researchers.</p>]]></description> </item><item><title><![CDATA[Adjuvant Therapies of COVID-19 - A Literature Review]]></title><link>https://www.benthamscience.comarticle/113537</link><description><![CDATA[Background: Coronavirus disease 2019 (COVID-19) was originated first in Wuhan, China, in December 2019, and it is known to be caused by severe acute respiratory syndrome coronavirus- 2 (SARS CoV-2). The management of COVID-19 could be achieved by means of the usage of the repurposed drugs, inhibiting the viral entry and/or viral fusion such as umifenovir, Baricitinib, Camostat mesylate, Nafamostat mesylate, and the drugs blocking the viral replication, which include favipiravir, remdesivir, Lopinavir/ritonavir, Ribavirin, Sofosbuvir, chloroquine and Hydroxychloroquine. <p> Objective: Along with the drugs that target the SARS-CoV-2 virus, adjunctive therapies are also employed. This review focuses on the adjuvant therapies employed to manage the COVID-19-associated complications, such as cytokine storm, acute respiratory distress syndrome (ARDS), respiratory failure, cardiac injury, coagulopathy, and multi-organ failure. <p> Methods: The literature was searched in databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, EMBASE, Directory of open access journals (DOAJ), and reference lists to identify relevant articles. <p> Results: Various studies have been identified for the use of corticosteroids, interferons, monoclonal antibodies, etoposide, ruxolitinib, anticoagulants, convalescent plasma, immunoglobulins, mesenchymal stem cells, natural killer (NK) cells, and inhaled nitric oxide (NO) as adjuvant therapy to manage the patients with COVID-19 along with the repurposed drugs targeting SARS-CoV-2. <p> Conclusion: The safety and efficacy of adjuvant therapy are needed to be confirmed by various ongoing randomized controlled clinical trials.]]></description> </item><item><title><![CDATA[Anti-drug Antibodies Monitoring in Biologics Use: Clinical Implications]]></title><link>https://www.benthamscience.comarticle/109979</link><description><![CDATA[<p>Background: Over the years, drug monitoring-such as Anti-Drug Antibodies (ADA) dosage- has witnessed major transformations. In fact, ADA are more and more used in rheumatology and gastro-enterology in monitoring chronic inflammatory disease therapeutic response. The main purpose of those researches is to produce less immunogenic drugs and, in consequences, to improve tolerance and efficiency since immunogenicity of those drugs still is the main constraint to their long-term use. The aim of this review was to highlight anti-drug-antibodies potential effects on the pharmacokinetics and bioavailability of biotherapies as well as their clinical implications. </P><P> Methods: For this purpose, we collected and summarized published data on PubMed using keywords “Biologics, Rheumatoid Arthritis, Spondyloarthritis, Crohn disease, Anti-drug antibodies, residual rate, immunogenicity, efficacy, tolerance”. The time-period selected for this study was 2000-2019. </P><P> Results: Anti-Drug-antibodies decrease the pharmaco-availability of drugs and, in consequences, its efficiency and high risk of refractory diseases and side effects. </P><P> Conclusion: Recent literature is consistent with the fact that drug monitoring using ADA dosage coupled with residual drug concentration offers reliable options to comfort practitioner’ therapeutic management decisions. This is particularly interesting in failure of treatment or in side effects onset situations.</p>]]></description> </item><item><title><![CDATA[The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases]]></title><link>https://www.benthamscience.comarticle/112994</link><description><![CDATA[<P>Background: The involvement of intercellular tight junctions and, in particular, the modulation of their competency by the zonulin pathway with a subsequent increase in epithelial and endothelial permeability, has been described in several chronic and acute inflammatory diseases. In this scenario, Larazotide, a zonulin antagonist, could be employed as a viable therapeutic strategy. </P><P> Objective: The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment. </P><P> Methods: A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: “Larazotide,” “Larazotide acetate,” “AT-1001,” “FZI/0” and “INN-202.” After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. </P><P> Results: The obtained publications were subdivided according to Larazotide’s mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other. </P><P> Conclusion: A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.</P>]]></description> </item><item><title><![CDATA[The Relevance of Supplemental Vitamin D in Malignancies]]></title><link>https://www.benthamscience.comarticle/113221</link><description><![CDATA[<p>Background: Vitamin D has a widely acknowledged role in regulating the metabolism of calcium and phosphate, both essential to bone remodeling. However, numerous studies in recent decades have emphasized the association between low sun exposure and vitamin D deficiency, and an increased risk of extra-skeletal disorders such as cancer. <p> Objective: This mini-review of literature aims to present an objective overview of several recent studies and meta- analyses evaluating the role of vitamin D in cancer prevention, its potential to improve cancer treatment outcomes, as well as the negative effects of vitamin D deficiencies. <p> Methods: The antitumor effects of calcitriol and analogs in the treatment of cancer, either as single agent or in combination with other anticancer agents, are based on several mechanisms: inhibition of cancer cell proliferation and invasiveness, induction of differentiation and apoptosis, and promotion of angiogenesis, all recorded in numerous preclinical studies of various cancer types. <p> Results: The importance of VDR polymorphisms for individual malignancies remains a topic of debate. Contradictory effects have been recorded in recent studies, the results of which include positive associations of VDR when cumulated with other risk factors, both an increase and a decrease in cancer risks, as well as no correlation between VDR polymorphisms and individual malignancies. <p> Conclusion: The scientific evidence reviewed in this paper suggests that health care providers and individuals should consider increasing concentrations of 25 (OH) D through sensitive sun exposure and / or by supplementing with vitamin D to reduce cancer risk and, in combination with standard care, to treat cancer.</p>]]></description> </item><item><title><![CDATA[Concomitant Diagnosis of Fibromyalgia and Ankylosing Spondylitis: Relation to Clinical Features and Plasma Pentraxin -3 Level]]></title><link>https://www.benthamscience.comarticle/113308</link><description><![CDATA[<p>Background: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disease that specifically affects the spine and sacroiliac joint. AS diagnosis is often delayed in the clinical practice and this delay may cause the patients to miss the chance of early treatment. Fibromyalgia (FM) is a frequently encountered clinical syndrome, fibromyalgianess is a term used when patients who are diagnosed with inflammatory arthropathies meet the criteria for FM syndrome as shown in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, and AS. </P><P> Objectives: We aimed primarily to assess the frequency of concomitant diagnosis of FM syndrome in AS patients and study its impact on clinical disease aspects. Secondary, our aim extended as a preliminary pilot study to assess the Plasma Pentraxin-3(PTX-3) as a potential marker for the diagnosis of FM syndrome in AS patients. </P><P> Methods: Plasma PTX-3 in 61 AS patients was compared to 60 matched controls. FM was diagnosed by FM Rapid Screening Tool. </P><P> Bath AS disease activity index (BASDAI) and AS disease assessment score using C- reactive protein (ASDAS-CRP), Bath AS functional impairment index (BASFI), Bath AS metrology index (BASMI), AS quality of life (ASQoL) scale, Beck Depression Inventory, and Bath AS Radiology Index (BASRI) were assessed. </P><P> Results: The patients were categorized into two groups according to the concomitant diagnosis of FM syndrome. Group I included 14 (22.9%) AS patients who fulfilled the clinical diagnosis of FM syndrome. Group II included 47 (77.1%) AS patients without FM syndrome. AS patients with FM (Group I) had significantly(p<0.001) increased an average of ages, disease duration, diagnostic delay of AS, switching of bDMARDs, morning stiffness duration, ASDAS-CRP, BASFI, ASQoL score, BASDAI (p=0.008), and BDI score (p=0.005) compared to AS patients without FM (Group II). PTX-3 levels were significantly (p<0.001) higher in Group I (p<0.001) (median, 0.23; IQR, 0.15-0.41 ng/ml) than Group II (median, 0.13; IQR, 0.035-0.21ng/ml) which showed no significant differences (p>0.05) compared to the controls. PTX-3 levels had significant positive correlations (p<0.05) with disease duration, BASFI, and ASQOl. Age, female sex, switch of biologic, ASDAS - CRP, and PTX-3 were significant predictors of FM in AS patients. </P><P> Conclusion: These results indicate that concomitant FM is a significant problem in patients with AS and its presence is associated with higher disease activity, impaired function as well as an overall negative impact on QoL. Easy scanning of suspicious cases of FM with FiRST questionnaire can be done in daily practice. PTX-3 is more or less accurate as the clinical features to improve the diagnostic certainty of FM in the presence of AS with a proven sensitivity of 62.3%, a specificity of 90%, a positive predictive value of 82.75%, and a negative predictive value of 73.9%.</p>]]></description> </item><item><title><![CDATA[A Case of Pulmonary Tuberculosis Mimicking as Diffuse Alveolar Hemorrhage: A Case Report]]></title><link>https://www.benthamscience.comarticle/115691</link><description><![CDATA[Background: Pulmonary tuberculosis (TB) and diffuse alveolar hemorrhage (DAH) have some commonalities in several parts of the world. However, acute hemoptysis with diffuse alveolar shadows while a patient is on anticoagulant and antiplatelet therapy for a specific reason suggests DAH over TB. <p> Case Presentation: In this case, a patient was presented with acute respiratory symptoms with hypoxia and bilateral alveolar shadows. He was treated for DAH at the initial encounter. However, on follow-up, he was confirmed having active pulmonary TB based on sputum acid-fast-bacilli culture. <p> Conclusion: He was successfully treated with standard first-line anti-tubercular therapy and was subsequently declared cured. Pulmonary DAH with TB, in the absence of an underlying autoimmune disorder, is rare.]]></description> </item><item><title><![CDATA[Regenerative Potential of Stem Cells Derived from Human Exfoliated Deciduous (SHED) Teeth during Engineering of Human Body Tissues]]></title><link>https://www.benthamscience.comarticle/112923</link><description><![CDATA[The current decade witnesses the regenerative potential of Stem Cells (SCs) based lifesaving therapies for the treatment of various disease conditions. Human teeth act as a reservoir for SCs that exist in high abundance in baby, wisdom, and permanent teeth. The collection of Stem cells from Human Exfoliated Deciduous teeth (SHED) is considered a simple process as it offers the convenience of little or no pain. In comparison to the SCs from dental or bone marrow or other tissues, the SHED offers the benefit of higher cellular differentiation and proliferation. Massive in vitro and in vivo studies reveal the regenerative potential of SHED in the engineering of the dental pulp tissue, neuronal tissue, root, bio root, cardiovascular tissues, lymphatic tissues, renal tissues, dermal tissues, hepatic tissues, and bone tissues. The current review describes the methods of collection/ isolation/storage, various biomarkers, and types of SHED. This review highlights the regenerative potential of SHED in the engineering of different tissues of the human body. As per the available research evidence, the present study supports that SHED may differentiate into the endothelial cells, neurons, odontoblasts, pancreatic &#946;-cells, hepatocytes, renal cells, fibroblasts, osteoblasts, and many other types of cells. The present study recommends that further clinical trials are required before the clinical application of SHED-based therapies.]]></description> </item><item><title><![CDATA[Asymmetric Dimethylarginine: a Key Player in the Pathophysiology of Endothelial Dysfunction, Vascular Inflammation and Atherosclerosis in Rheumatoid Arthritis?]]></title><link>https://www.benthamscience.comarticle/113105</link><description><![CDATA[Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.]]></description> </item><item><title><![CDATA[The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine]]></title><link>https://www.benthamscience.comarticle/111192</link><description><![CDATA[<p>Background: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease. </P><P> Objective: Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice. </P><P> Methods: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation. </P><P> Results: In MIF-/-mice, TAA reduced transaminases, &#947;-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-&#947;, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols. </P><P> Conclusion: MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.</p>]]></description> </item><item><title><![CDATA[Dysfunctional High-density Lipoprotein: The Role of Myeloperoxidase and Paraoxonase-1]]></title><link>https://www.benthamscience.comarticle/108200</link><description><![CDATA[Low circulating high-density lipoproteins (HDL) are not only defining criteria for metabolic syndrome, but are more generally associated with atherosclerotic cardiovascular disease (ASCVD) and other chronic diseases. Oxidative stress, a hallmark of cardio-metabolic disease, further influences HDL activity by suppressing their function. Especially the leukocyte- derived enzyme myeloperoxidase (MPO) has recently attracted great interest as it catalyzes the formation of oxidizing reactive species that modify the structure and function of HDL, ultimately increasing cardiovascular risk. Contrariwise, paraoxonase-1 (PON1) is an HDL-associated enzyme that protects HDL from lipid oxidation and then acts as a protective factor against ASCVD. It is noteworthy that recent studies have demonstrated how MPO, PON1 and HDL form a functional complex in which PON1 partially inhibits the MPO activity, while MPO in turn partially inactivates PON1.In line with that, a high MPO/PON1 ratio characterizes patients with ASCVD and metabolic syndrome and has been suggested as a potential marker of dysfunctional HDL as well as a predictor of ASCVD. In this review, we summarize the evidence on the interactions between MPO and PON1 with regard to their structure, function and interaction with HDL activity. We also provide an overview of in vitro and experimental animal models, finally focusing on clinical evidence from a cohort of patients with ASCVD and metabolic syndrome.]]></description> </item><item><title><![CDATA[Cutaneous Autoimmune Phenomena of the Anti-TNFa Biosimilars. Casebased Review]]></title><link>https://www.benthamscience.comarticle/111667</link><description><![CDATA[Background: Psoriasis (Pso) is a common chronic inflammatory disease affecting the skin, both sexes, and all ages. It can be associated with other chronic inflammatory musculoskeletal disorders and certain drugs, including tumor necrosis factor &#945; (TNF&#945;) antagonists. </p> Case Presentation: A 64-year-old man with seronegative rheumatoid arthritis (RA) refractory to leflunomide and prednisone was treated with SB-4 (Benepali), an etanercept biosimilar 50mg/week subcutaneously. He responded well to the treatment, but a year later, he developed erythematous skin eruptions affecting mainly in the palms of both hands. Skin biopsy showed a picture compatible with Pso. SB-4 was discontinued, and the skin lesions disappeared with the addition of topical steroid therapy. This is the only case of psoriatic skin lesions associated with SB-4 treatment. </p> Conclusion: Thus, we review and discuss the relevant literature of Pso cases related to SB-4 and other anti-TNF&#945; biosimilars. Rheumatologists dealing with patients on anti-TNF&#945; biosimilars should be aware of and recognize these complications.]]></description> </item><item><title><![CDATA[Deciphering Role of Cytokines for Therapeutic Strategies Against Rheumatoid Arthritis]]></title><link>https://www.benthamscience.comarticle/110950</link><description><![CDATA[Rheumatoid Arthritis (RA) is a systemic, chronic, autoimmune, inflammatory disorder that affects both large and small synovial joints in a symmetric pattern. RA initiates as painful inflammation of the joints leading to stiffness of joint, joint destruction and further worsens the condition causing permanent irreversible damage to the joints, making them physically disabled. Across the globe, there are around 1.2 million cases of RA reported. Inspite of various available therapeutic and pharmacological agents against RA, none of the treatments assure complete cure. Understanding the in depth-role of cytokines and interleukins in the disease pathogenesis of RA could help in exploiting them for developing novel therapeutic strategies against RA. This review provides insights into the pathogenesis of RA and gives a brief overview of cytokines, which play an important role in the progression of the disease. We have also discussed the possible role of interleukins in the context of RA, which could help future researchers to explore them for identifying new therapeutic agents.]]></description> </item><item><title><![CDATA[Current Therapeutic Options for the Treatment of Juvenile Idiopathic Arthritis]]></title><link>https://www.benthamscience.comarticle/110031</link><description><![CDATA[Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease and an exclusion diagnosis that includes all forms of arthritis that persists for more than 6 weeks under the age of 16. Although there is not yet a cure for JIA, and recent advances in the therapeutic field have created a more hopeful present and future for the patients. In the past, therapies for JIA have depended on non-steroidal medication, conventional synthetic disease-modifying antirheumatic drugs and corticosteroids. However, over the last decades, the advent of biologic therapies in JIA contributed to the preservation of functional activity, control of pain, avoidance of joint damage, and extra-articular manifestations. Furthermore, over the last years, international institutions, such as the American College of Rheumatology, have released recommendations and guidelines for rheumatologists for optimal JIA management. All the above have revolutionized the treatment of JIA with promising outcomes. To this end, the relevant literature is reviewed and discussed appropriately.]]></description> </item><item><title><![CDATA[Distinctive Features in Spondyloarthritis Between Women and Man in Moroccan Context: Disease Beginning, Clinical Manifestations, Disease Activity and Function Scores]]></title><link>https://www.benthamscience.comarticle/99221</link><description><![CDATA[<P>Background: Axial spondyloarthritis (axSpA) is a common group of chronic rheumatic inflammatory diseases, which usually affects the axial skeleton, and are more frequently observed in males than in females. Several differences have been brought up in the clinical presentation of axSpA, according to the patient’s gender. In fact; axSpA severity in women tends to be moderate, leading then, to an underdiagnosis in this category of patients. While male axSpA patients seem to set forth more spinal destructions on radiographs. </P><P> Objective: As the main goal, our study aims to bring up the particularities of female axial spondyloarthritis, all the while comparing them with the male form. </P><P> Materials and Methods: This is a cross-sectional study carried out in the period lying between January 2012 and December 2017, at a single rheumatology department in Morocco. All patients with an axial spondyloarthritis meeting the Assessment of SpondyloArthritis international Society (ASAS) classification criteria 2010, and who have been admitted in our department, during that period, were included. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis. A value of p <0.005 has been used to identify factors associated with axSpA in women. </P><P> Results: A total of 277 patients were enrolled, of which 147 are female and 130 are male with a sex ratio of 1.1. Cervical stiffness was more common in men. On the other hand, women had more arthritis and enthesitis. However, no considerable divergences have been underscored between the two genders, neither in the prevalence of extra-articular manifestations, nor in disease activity BASDAI and BASFI. Men had more radiographic sacroiliitis compared to women (57.5% vs. 42.5%, p=0.01), more coxitis (66.7% vs. 33.3%, p = 0.0001). The Multivariate logistic regression analysis showed that female gender was associated with a greater age at the diagnosis onset (IC: 1.053-1.103, OR=1.07, p=0.001) and arthritis (IC: 2.37-4.26, OR=2.3, p=0.004). While the male sex was associated with a young age of onset (CI: 4.50-19.52, OR = 9.3), coxitis (CI: 2.53-4.23, OR = 3.3) and smoking (CI: 15.667-900.18, OR = 118.7). </P><P> Conclusion: The comparison between male and female patients suffering from axial spondyloarthritis found many differences and similarities as well, in the disease expression. This study showed actually that women had the less severe form of spondyloarthritis.</P>]]></description> </item><item><title><![CDATA[The Role of Endostatin in Rheumatoid Arthritis]]></title><link>https://www.benthamscience.comarticle/106227</link><description><![CDATA[<P>Background: Endostatin by its therapeutic value against rheumatoid arthritis has recently gained significant interest in biomedical science. A recent study revealed that various approaches have been made to prevent rheumatoid arthritis by either controlling or inhibiting the progression of angiogenesis. </P><P> Objective: The main objective of the current manuscript is to enumerate the intrinsic role of endostatin in rheumatoid arthritis. </P><P> Methods: A thorough and detailed review of literature from the papers published from the year 1997-2019 was studied for the preparation of the current article. </P><P> Results: Endostatin is one such agent of the subfamily of ECM called as multiplexins obtained from proteolytic cleavage of XVIII and its carboxylic terminal fragments and is known for its antiangiogenic and antiproliferative property. The exact mechanism of endostatin is still unclear, but it acts by downregulating or inhibiting the responses of various factors, including Id1, Id3, matrix metalloproteinase, and Nuclear factor Kappa B that are liable for angiogenesis. The mutual effects on adipogenesis and angiogenesis, endostatin inhibits dietary-induced obesity and its related metabolic disorders, such as insulin resistance, glucose intolerance, and hepatic steatosis. </P><P> Conclusion: The present review demonstrates the intrinsic usage of endostatin as a novel molecule in rheumatoid arthritis. It focuses on the status of the therapeutic potential of endostatin in inhibiting the activity of angiogenesis is also very well explored.</P>]]></description> </item><item><title><![CDATA[Atherogenic Index of Plasma in Women with Rheumatoid Arthritis and Systemic Lupus Erythematosus: A 10-Year Potential Predictor of Cardiovascular Disease]]></title><link>https://www.benthamscience.comarticle/110523</link><description><![CDATA[<P>Background: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are at high risk of cardiovascular diseases (CVD). The atherogenic index of plasma (AIP) is a new marker for the assessment of CVD. </P><P> Objective: This study aimed to determine the predictive value of AIP with long-term CVD risk among women with RA and SLE. </P><P> Methods: This is a cross-sectional study of 99 RA and 59 SLE women. Demographic, clinical, and biochemical data were obtained, and disease activities were calculated. For each patient, the longterm risk of CVD was calculated using the Framingham risk score (FRS); AIP was derived according to the logarithmic (triglycerides/high-density lipoproteins cholesterol). </P><P> Results: The mean age of the RA and SLE patients was 47.97 ± 8.78 and 36.75 ± 9.09 years, respectively. The median (interquartile range) of AIP values in RA and SLE patients were 0.34 (-0.15, 1.02) and 0.33 (-0.53, 0.96), respectively, while FRS values of RA patients and SLE patients were 6.38 ± 5.58 and 4.86 ± 4.5, respectively (p >0.05). There was a moderate correlation between AIP and FRS in RA and SLE patients (r=0.42, p=0.002 and r=0.33, p=0.007, respectively). According to the multivariate regression analyses, we found that AIP value is an independent factor for FRS in RA (&#946;: 4.13, 95% confidence interval; 1.71, 6.18; p=0.008) and in SLE patients (&#946;: 6.19, 95% confidence interval; 2.58, 9.81; p<0.001). </P><P> Conclusions: We reported that AIP can be used as an independent indicator for long-term CVD risk in RA and SLE patients.</P>]]></description> </item><item><title><![CDATA[Advances in Microbiome Detection Technologies and Application in Antirheumatic Drug Design]]></title><link>https://www.benthamscience.comarticle/112357</link><description><![CDATA[Rheumatic diseases are a kind of chronic inflammatory and autoimmune disease affecting the connection or supporting structures of the human body, such as the most common diseases Ankylosing spondylitis (AS), gout and Systemic lupus erythematosus (SLE). Although the precise etiology and pathogenesis of the different types of rheumatic diseases remain mostly unknown, it is now commonly believed that these diseases are attributed to some complex interactions between genetics and environmental factors, especially the gut microbiome. Altered microbiome showed clinical improvement in disease symptoms and partially restored to normality after prescribing disease-modifying antirheumatic drugs (DMARDs) or other treatment strategies. Recent advances in next-generation sequencing-based microbial profiling technology, especially metagenomics, have identified alteration of the composition and function of the gut microbiota in patients. Clinical and experimental data suggest that dysbiosis may play a pivotal role in the pathogenesis of these diseases. In this paper, we provide a brief review of the advances in the microbial profiling technology and up-to-date resources for accurate taxonomic assignment of metagenomic reads, which is a key step for metagenomics studies. In addition, we review the altered gut microbiota signatures that have been reported so far across various studies, upon which diagnostics classification models can be constructed, and the drug-induced regulation of the host microbiota can be used to control disease progression and symptoms.]]></description> </item><item><title><![CDATA[TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis]]></title><link>https://www.benthamscience.comarticle/104926</link><description><![CDATA[<P>Background: Clinical studies indicate that recombinant tumor necrosis factor receptor:Fc fusion protein (rhTNFR:Fc) quickly alleviates symptoms and physical signs of active Ankylosing Spondylitis (AS), improving the manifestation of spinal inflammation on radiological imaging. However, the regulatory mechanism of rhTNFR:Fc in the chemokine pathway is unclear. Thus we study the mechanism of phlogogenic activity of CXCL16/CXCR6 in AS and the related mechanism of rhTNFR: Fc treatment. </P><P> Methods: Thirty-two cases of active AS were treated with rhTNFR:Fc for 3 consecutive months. Clinical response was evaluated at baseline and after treatment. CXCL16/CXCR6 expression as well as Receptor Activator Of Nuclear Factor-Κb Ligand (RANKL)/Osteoprotegerin (OPG), essential molecules for osteoclast differentiation, were studied in AS before and after treatment. Further, the proliferation of lymphocytes and the RANKL level stimulated by recombinant human CXCL16 (rhCXCL16) were measured in vitro. </P><P> Results: Thirty cases responded to rhTNFR:Fc treatment. The RANKL level, RANKL/OPG ratio, CXCLl6 level in serum, and CXCLl6 and CXCR6 mRNA levels in active AS were higher than those in controls and treated patients (P<0.001). rhCXCL16 treatment increased lymphocyte proliferation and RANKL level in active AS (P<0.001), but not in controls or treated patients (P>0.05). A positive linear correlation was noted between CXCL16 serum levels and RANKL/OPG ratio and between CXCL16 levels and C-reactive protein results (P<0.001). </P><P> Conclusions: Our findings suggest that rhTNFR:Fc suppresses inflammation and bone destruction of AS by reducing the RANKL/OPG ratio through inhibition of the CXCL16/CXCR6 pathway.</P>]]></description> </item><item><title><![CDATA[Evaluation of the Oxidative Stress Level and Serum Prolidase Activity in Patients with Sleep Bruxism]]></title><link>https://www.benthamscience.comarticle/108631</link><description><![CDATA[<P>Aim and Objective: Sleep bruxism is a complicated disease, and its cause remains controversial. If the etiology of bruxism is resolved, the treatment can be adjusted to the prevailing aetiological factor. Thus, the aim of this study was to evaluate the oxidative stress level and serum prolidase activity in patients with sleep bruxism. </P><P> Materials and Methods: Seventy healthy subjects and 51 patients with sleep bruxism were included in this study, and blood samples from all patients were collected. Serum samples were analyzed for total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and prolidase activity. </P><P> Results: The prolidase, TOS, and OSI levels were significantly higher in patients with bruxism than in the healthy controls (p = 0.001, p = 0.001, p = 0.001, respectively). The TAS level was significantly lower in bruxism patients than in healthy controls (p = 0.003). </P><P> Conclusion: The increased TOS, OSI, and prolidase levels and decreased TAS levels could be assumed to result in oxidative injury in patients with sleep bruxism. However, the study could not determine whether oxidative imbalance and increased serum prolidase levels could be a cause or a result of bruxism.</P>]]></description> </item><item><title><![CDATA[Novel Aceclofenac Cocrystals with l-Cystine: Virtual Coformer Screening, Mechanochemical Synthesis, and Physicochemical Investigations]]></title><link>https://www.benthamscience.comarticle/109138</link><description><![CDATA[<P>Aim: Current work focuses on the improvement of the solubility and dissolution of ACF by the cocrystal approach. </P><P> Background: Aceclofenac (ACF) is one of the commonly used Nonsteroidal Anti-Inflammatory Drug (NSAID) representing a variety of therapeutic applications including management of pain, inflammation, rheumatoid arthritis, and osteoarthritis, <i>etc</i>. But very low solubility and dissolution rate of ACF compromise its therapeutic utility. Now a day’s cocrystallization technique has emerged as a novel technique for modulation of the said problems. </P><P> Objective: The Specific objectives of this research work were mechanochemical synthesis, characterization, and performance evaluation of aceclofenac cocrystal. </P><P> Methods: ACF was screened with various pharmaceutically acceptable coformers (Selected from GRAS and EAFUS list) using MOPAC software and physical screening method to find out novel cocrystals of ACF with enhanced solubility and dissolution rate. Novel cocrystals (multi-component crystalline solid) of ACF with l-cystine were prepared by a neat grinding method and by liquid assisted grinding method. The synthesized cocrystals (ACF-l-CYS NG and ACF-l-CYS LAG) were characterized carefully by Differential Scanning Calorimetry (DSC), Infrared Spectroscopy (IR), and Powder XRay Diffraction (PXRD) to verify the formation of the cocrystals. Pharmaceutically significant properties such as powder dissolution rate, solubility, and stability of the prepared cocrystals were evaluated. </P><P> Results: Compared to pure ACF, the prepared cocrystals showed superior solubility and dissolution rate. The prepared cocrystals were found to be stable and non-hygroscopic under study conditions. </P><P> Conclusion: The cocrystallization technique was successfully utilized to increase the solubility and dissolution rate of aceclofenac.</P>]]></description> </item><item><title><![CDATA[Monoclonal Antibodies: A Prospective and Retrospective View]]></title><link>https://www.benthamscience.comarticle/104666</link><description><![CDATA[<P>Background: Monoclonal Antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, angiogenesis-related diseases and, more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering. </P><P> Objectives: The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends. </P><P> Results: We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables. </P><P> Conclusion: The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.</P>]]></description> </item><item><title><![CDATA[Medicinally Privileged Sultams: Synthesis and Mechanism of Action]]></title><link>https://www.benthamscience.comarticle/108270</link><description><![CDATA[To date, more than a thousand research articles have been published detailing various regio-, stereo-, chemo-, and enantioselective specific synthesis of the cyclic sulfonamides (sultams). Although enormous synthetic efforts were made, but bioactivities of sultams have not been widely investigated. Sultams are the sulfur analogs of lactams (cyclic amides) which demonstrate a broad range of medicinal activities and several lactam drugs are commercially available. In contrast, only a few sultam drugs are commercially available, while the presence of two oxygens on sulfur in sultam motifs can serve as a better H-bond acceptor than lactam scaffolds. One of the major objectives of this minireview is to draw appropriate attention from the medicinal/pharmaceutical chemists to conduct indepth research on sultam derivatives targeted to the development of new drugs. This article gives a brief account of the synthesis, potential bioactivity, and mechanisms of therapeutic action of four to seven-membered sultam derivatives. Based on the available literature, this is the first effort to consolidate only the medicinally privileged sultam molecules and drugs under the same umbrella. While every effort was taken to comprise all the relevant reports related to bioactive sultams, any oversight is truly unintentional.]]></description> </item><item><title><![CDATA[Health-Related Quality of Life in Patients with Ankylosing Spondylitis: Relationship with Disease-Related Variables]]></title><link>https://www.benthamscience.comarticle/101629</link><description><![CDATA[<p>Background: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease leading to functional limitations and subsequently impaired quality of life (QoL). Despite the fact that QoL was recognized as a significant perception, it was excluded from the core domains (defined by the Assessment of Spondyloarthritis International Society), because of ambiguity of measurement choice. </P><P> Aim: To assess QoL in patients with AS using a generic; Short Form-36 (SF-36) and a diseasespecific; Ankylosing Spondylitis quality of life (ASQoL) instruments and to explore its relationship to the clinical characteristics, disease activity, functional status, and radiographic severity. </P><P> Methods: A total of 47 AS patients who fulfilled modified New York criteria were included. Disease activity, functional status, spinal mobility, and radiographic severity were assessed by Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI) and Bath AS Radiology Index (BASRI) respectively. SF-36 and ASQoL instruments evaluated Qol. </P><P> Results: Physical health was more affected especially in patients with peripheral arthritis by SF-36 (p=0.008) and ASQoL (p=0.022) scores. Both SF-36 total and ASQoL scores correlated significantly with BASDAI (r = -0.329, p = 0.024 and r = 0.420, p = 0.003), BASFI (r = -0.399, p = 0.005 and r = 0.513, p=0.001) and BASMI (r = -0.382, p = 0.008 and r = 0.482, p= 0.001) respectively. </P><P> Conclusion: QoL was impaired in AS patients with highest impact on physical health especially in association with peripheral arthritis. SF-36 and ASQol have a comparable achievement in the evaluation of QoL in AS patients and both physical function and spinal mobility were identified as predictors of poor QoL.</p>]]></description> </item></channel></rss>