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.

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.

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.

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.

Method: 34 patients in the drug group received 4 capsules of Mastic pill plus Omeprazole capsule 20 mg daily. 34 patients in the placebo group received the same dosing of Omeprazole and placebo. The medication was given to patients for a total duration of 4 weeks. All patients were requested to fill out the modified GERD-HRQL questionnaire at the beginning and every two weeks for a total duration of six weeks.

Result: Reflux, and heartburn severity score as well as disruption of personal life score significantly reduced in both groups, but it was more remarkable in the drug group (P-value = 0.0001). Dysphagia, early satiation, and nausea significantly reduced in the drug group while the placebo group showed no improvement. Our results suggest that constipation, bloating, belching, and odynophagia did not significantly improve in none of the groups.

Conclusion: This study showed that Habb-e-Mastaki is effective against GERD. Further detailed in vitro and in vivo studies aimed at discovering the mechanism of action of this formulation and clinical studies involving a larger population will be necessary to explain and confirm the results obtained in the present study.

Introduction: An analysis of ACE inhibitors and colon cancer is conducted in this comprehensive review. The main goal is to see how ACEIs/ARBs affect the chances of getting cancer and dying in patients with CC.

Methods: A systematic literature search was conducted to identify relevant studies. Inclusion criteria encompassed studies that evaluated the use of ACEIs/ARBs in patients with CC and reported outcomes related to new cancer incidence and mortality. Data from selected studies were extracted and analyzed using appropriate statistical methods.

Results: The study showed that fewer cancer cases occurred in patients who took ACEIs/ARBs compared to those who did not (RR 0.962, 95% CI 0.934-0.991, p = 0.010). Furthermore, patients with CC who utilized ACEIs/ARBs exhibited a decreased mortality rate compared to non-users (HR 0.833, 95% CI 0.640-1.085, p = 0.175).

Conclusion: This review suggests that using ACEIs/ARBs medicine could help people with CC live longer and lower their chances of dying. These results highlight the potential benefits of utilizing ACE inhibitors in the management of CC, warranting further investigation and consideration in clinical practice.

In this State-of-the-Art review, we provide comprehensive insights into the complex pathobiology of PAH to provide understanding and insights for the practicing clinician. We review the pathology of PAH and the cells involved and their impact in driving pathological abnormalities (pulmonary artery endothelial cells, smooth muscle cells, fibroblasts and pericytes) as well as the role of the extracellular matrix. Inflammation and immune dysfunction are considered important drivers of PAH and are comprehensively discussed. Another pathway relates to TGFβ/ bone morphogenic protein (BMP) imbalance, which is highlighted, as well as a new novel agent, sotatercept that impacts this imbalance. Genetic factors underlying heritable PAH (HPAH) are addressed, as well as epigenetic influences. Other important pathways highlighted include growth factor signaling, ion channels/channelopathy, hypoxia signaling pathways, and altered metabolism and mitochondrial dysfunction. We also address the “estrogen paradox”, whereby PAH is more common in women but more severe in men. The basis for drug-induced PAH is discussed, including the new methamphetamine epidemic. We briefly provide insights into DNA damage and senescence factors in pathobiology and highlight commonalities between PAH and cancer pathobiology. Furthermore, we provide concluding insights for the treating physician. In conclusion, we need to pose the right questions to motivate novel and effective treatment strategies for the management of PAH based on pathobiological principles and understanding.

Understanding of the disease has improved through registries, classifying it into five distinct groups with similar histology, pathophysiology, and therapeutic approaches. These groups include PAH, with heritable and idiopathic causes, as well as various clinical subsets involving connective tissue disease, HIV, portopulmonary hypertension, congenital heart disease, and schistosomiasis. Long-term responders to calcium channel blockers, PAH with venous/capillaries involvement, and persistent PH of newborns are categorized under Group 1, now re-classified as IPAH.

A comprehensive workup for suspected patients includes various tests like electrocardiogram, pulmonary function testing, autoimmune workup, HIV testing, echocardiogram, right heart catheterization, and cardiopulmonary exercise testing.

This review emphasizes the disease's definition and epidemiology, delving into each subset and providing updated workup guidelines. The subsequent article will focus on risk stratification and treatment strategies.

Case Presentation: The annual incidence of MCTD is 1.9 per 100,000 adults. Any organ system can be involved in MCTD however four clinical features that suggest the presence of MCTD rather than another systemic rheumatic disease are Raynaud phenomenon with swollen hands or puffy fingers, absence of severe kidney disease and central nervous system (CNS) disease at first presentation generally, insidious onset of pulmonary hypertension and presence of autoantibodies anti-U1 ribonucleoprotein (U1 RNP), especially antibodies to the 68 kD protein. MCTD, although initially thought to be a disease with a benign course is not considered a valid argument at present. This connective tissue disorder can present with life-threating organ involvement with rapid progression of disease.

Conclusion: We report two cases of MCTD, one with mild disease and another with life-threatening illness, describing the range of severity at presentation of this disorder.

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.

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.

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.

Case Presentation: Mutilating arthritis (arthritis mutilans) can be part of the clinical presentation of a number of rheumatic diseases, most commonly seen in psoriatic arthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, but also in systemic lupus, systemic sclerosis, and multicentric reticulohistiocytosis. Evidence exists that subperiosteal and subchondral bone resorption, seen in PHPT, could induce the so-called ‘osteogenic synovitis’, which could eventually lead to the development of a secondary osteoarthritis with bone deformities.

Conclusion: Here, we present a case report of a patient initially diagnosed with PHPT who presented with mutilating arthritis of the finger joints and discuss whether the severe acro-osteolysis is a manifestation of the endocrinopathy or whether there is a co-existing undiagnosed inflammatory joint disease.

Case Presentation: We describe a 58-year-old woman with seronegative RA, refractory to methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was discontinued and two months later, she had substantial skin improvement.

Conclusion: This is the first report of morphea manifestation during TNFi biosimilar since the patient had no other trigger factors for morphea development like trauma and infections. Physicians dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions, among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow- up check are required.

Objective: The aim of the study was to assess the presence of differentiating features between “scleroderma” pattern in SSc and “scleroderma-like” pattern in other rheumatic diseases.

Methods: 684 capillaroscopic images demonstrating a “scleroderma” and “scleroderma-like” pattern have been analysed in the current retrospective cross-sectional study. 479 capillaroscopic pictures were obtained from 50 SSc patients, 105 from 7 DM patients, 38 from 10 rheumatoid arthritis (RA) patients, 36 images from 5 patients with SLE, and 26 images from 9 patients with UCTD. All capillaroscopic images used in the current analysis have fulfilled the criteria for “sclerderma/scleroderma-like” pattern, as the pathological changes in the capillaroscopic parameters have also been confirmed by quantitative measurement of capillary diameters, capillary density, and intercapillary distance. All the images have been categorized into one of the following groups, i.e., “early”, “active” and “late” phases (according to the definition of Cutolo et al.), or “other” findings, the latter being specifically described as they could not be attributed to one of the other three categories.

Results: 479 capillaroscopic pictures were obtained from 50 scleroderma patients. 31 of them showed an “early”, 391 an “active” phase, and 57 a “late” phase “scleroderma” type microangiopathy. In 69 images assessed as an “active” pattern, neoangiogenesis was found. In 43 out of 105 capillaroscopic pictures from DM patients, an “active” phase was detected; in 2 of the images, a “late” pattern was found, and in 60 capillaroscopic pictures, neoangiogenesis in combination with giant capillary loops was observed. Early microangiopathy was not found in this group. Among capillaroscopic images from SLE patients, “late” phase microangiopathy was not found. “Early” phase was present in 3 images, “active” phase in 29, neoangiogenesis in “active” phase in 4 pictures. Early microangiopathy was detected in 11 capillaroscopic pictures from RA patients (8 out of 9 patients), an “active” phase in 4 images (3 patients), and in 23 capillaroscopic images, neoangiogenesis with mild capillary derangement and capillary loss and single giant capillaries (“rheumatoid neoangiogenic pattern”) were observed. Classic “late” type microangiopathy was not found in RA patients as well as among patients with UCTD. The predominant capillaroscopic pattern in UCTD patients was early microangiopathy (n = 23). The rest images from UCTD exhibited features of the “active” phase.

Conclusion: In conclusion, early microangiopathy was observed in RA, SLE, and UCTD patients, but not in patients with DM. An “active” phase “scleroderma” type capillaroscopic pattern was detected in all patient groups other than SSc, i.e., DM, SLE, RA, and UCTD. “Late” phase “scleroderma” type microangiopathy was present in patients with scleroderma and DM and was not observed in SLE, RA, and UCTD. Despite the fact that in some cases, microangiopathy in scleroderma and other rheumatic diseases may be indistinguishable, the results of the current research have shown the presence of some differentiating features between “scleroderma” and ”scleroderma-like” microangiopathy that might be a morphological phenomenon associated with differences in the pathogenesis and the degree of microvascular pathology in various rheumatic diseases.

Pulmonary hypertension (PH) encompasses a set of multifactorial diseases of progressive cardiopulmonary disorder. WHO classifies PH into five groups based on similar pathophysiological mechanisms, clinical presentation, haemodynamic characteristics, therapeutic management, and underlying etiology. Since PH shows many similarities with cancer, such as proliferation, resistance to apoptosis, and dysregulation of tumor suppressor genes, the current epigenetics therapeutic strategies used in cancer might be considered for the treatment of PH. The role of epigenetics in the setting of PH is a fast-growing field of research. In this review, we have summarized the up-to-date articles on the role of epigenetic mechanisms in the context of PH. The aim of this review is to provide a comprehensive insight from the epigenetics perspective and introduce the potential role of approved epi drugs in PH treatment.

Objective: To test the hypothesis that those fibromyalgia patients who are ANA seropositive are more likely to show evidence of Borrelia-specific T lymphocyte reactivity than those who are seronegative.

Methods: T lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen) was assessed using the enzyme-linked immunospot and serum ANA status was assessed using immunofluorescence in 27 fibromyalgia patients fulfilling the revised diagnostic criteria of the American College of Rheumatology.

Results: The ANA seropositive and seronegative groups were matched for age, sex and ethnicity; the T lymphocyte reactivity to Borrelia burgdorferi sensu stricto (full antigen) in the former group (mean 5.60) was significantly higher than that in the seronegative group (mean 1.77; p < 0.05).

Conclusion: This novel study points to an association of ANA seropositivity in fibromyalgia with Borrelia-specific T lymphocytes.

Methods: A cross-sectional study was undertaken on thirty-four adult SSc patients who met the 2013 ACR/EULAR criteria for SSc and Forty healthy controls of matched age and sex. The patients were subjected to history taking, clinical examination, skin assessment using the modified Rodnan Skin Score (mRSS), chest x-ray (CXR), pulmonary function test (PFTs), and high resolution computed tomography of the chest (HRCT). Routine laboratory tests were conducted in addition to immunologic tests and an enzyme-linked immunosorbent assay (ELISA) to determine the IL-33 level.

Results: ILD was found in 23 SSc patients (67.6%); 20 patients had diffuse type while 3 patients had limited type. Non-specific interstitial pneumonia (NSIP) was found in 56.5%, usual interstitial pneumonia (UIP) was found in 21.7%, pleuroparenchymal fibroelastosis (PPFE) was found in 8.7%, and organizing pneumonia (OP) with the mixed pattern was found in 13% of SSc patients. Additionally, the mean IL-33 level in SSc patients was 98±12.7 compared to 66.2±10.6 in the control group (p < 0.001), with ILD patients having a significantly higher level (101.7±13.4) than those without (90.4±6.2), and a strong positive correlation with mRSS.

Conclusion: Even in asymptomatic patients with SSc, ILD is prevalent, with NSIP being the most common pattern. IL-33 could be considered a potential biomarker for predicting the presence of ILD in SSc patients.

Results: 27 patients with SS and LIP were found. The age range ranged from 14 to 73 years old, with only 3 male patients, with a predominance of LIP cases in patients with primary SS (22/27). In the following case, the LIP preceded SS by 2 years; in the other 26 patients, SS preceded it. The majority presented dyspnea, mainly on exertion, followed by a dry cough. Lung biopsy was performed in 10 studies. Therapy varied from the use of clinical observation, corticosteroids alone, or associated with immunosuppressants. Most studies have shown improvement or stabilization of the pulmonary condition after therapy (13/16 studies).

Conclusion: This article reviews cases of lymphocytic interstitial pneumonia associated with Sjögren syndrome and shows a good outcome with adequate treatment. It emphasizes that early LIP diagnosis in patients with Sjogren Syndrome may be determined using lung computed tomography.]]> https://www.benthamscience.comarticle/124056 Methods: Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes.

Results: No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma.

Conclusion: Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.]]> https://www.benthamscience.comarticle/123052Background: Early recognition of acanthosis nigricans is important because acanthosis nigricans can be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy.

Objective: The purpose of this article is to familiarize pediatricians with the clinical manifestations, evaluation, diagnosis, and management of acanthosis nigricans.

Methods: A search was conducted in November 2021in PubMed Clinical Queries using the key term \"acanthosis nigricans\". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.

Results: Acanthosis nigricans is characterized by symmetric, hyperpigmented, and velvety plaques with ill-defined borders, typically involving intertriginous areas. Obesity is the most common cause of acanthosis nigricans which is increasingly observed in obese children and adolescents and can serve as a cutaneous marker of insulin resistance. Early recognition of acanthosis nigricans is important because acanthosis nigricans can also be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy. This may consist of weight reduction, discontinuation of causative drugs, treatment of underlying endocrinopathy, or treatment of an underlying malignancy. For patients with isolated acanthosis nigricans and for those whose underlying cause is not amenable to treatment, treatment of the lesion may be considered for cosmetic reasons. Topical retinoids, vitamin D analogs, chemical peels, and other keratolytics are often used for the treatment of localized lesions. Seldom, systemic therapy such as oral retinoids may be considered for extensive or generalized acanthosis nigricans and acanthosis nigricans unresponsive to topical therapy. Other uncommon treatment modalities include dermabrasion, laser therapy, and surgical removal.

Conclusion: Although acanthosis nigricans is treatable, a complete cure is difficult to achieve. The underlying cause should be treated, if possible, to resolve and prevent the recurrence of acanthosis nigricans. The diagnosis is mainly clinical, based on the characteristic appearance (symmetrically distributed, hyperpigmented, velvety, papillomatous, hyperkeratotic plaques with ill-defined borders) and the typical sites (intertriginous areas, flexural area, and skin folds) of the lesions. The diagnosis might be difficult for lesions that have atypical morphology or are in an unusual location. Clinicians should be familiar with the clinical signs, evaluation, diagnosis, and therapy of acanthosis nigricans because of the link between it and underlying diseases.

Objective: In this review, a risk/benefit analysis is performed on OSM inhibition in the context of atherosclerosis treatment. First, OSM signaling characteristics and its role in atherosclerosis are described. Next, an overview of in vitro, in vivo, and clinical findings relating to both the benefits and risks of modulating OSM in major organ systems is provided. Based on OSM’s biological function and expression profile as well as drug intervention studies, safety concerns of inhibiting this target have been identified, assessed, and ranked for the target population.

Conclusion: While OSM may be of therapeutic value in atherosclerosis, drug development should also focus on de-risking the herein identified major safety concerns: tissue remodeling, angiogenesis, bleeding, anemia, and NMDA- and glutamate-induced neurotoxicity. Close monitoring and/or exclusion of patients with various comorbidities may be required for optimal therapeutic benefit.

Methods: This study concerned the analysis of 14 Caucasian patients in two groups: ten patients enrolled in the Digestive Diseases Unit, University of Catanzaro (Italy), and four patients enrolled in the Department of Hepatology, University Hospital Kràlovskè Vinohrady of Prague (Czech Republic). The statistical analysis was performed using the software IBM SPSS (v. 20, Windows).

Results: The Italian group showed a statistically significant difference in the total bilirubin values at diagnosis and during the last control (0.74±0.267 vs. 0.56±0.246; p-value: 0.013). Moreover, the comparison between the two groups showed a statistically significant difference in the serum albumin values at the time of the last control (4.6±0.231 vs. 4.15±0.532; p-value: 0.048).

Conclusion: Our data indicate an effective difference in the onset and clinical presentation between our two groups. More epidemiologic, prospective, and multicenter research projects are warranted to advance PBC knowledge in Europe.]]> https://www.benthamscience.comarticle/119148Background: Disability in patients with scleroderma (SSc) has been associated with poor health-related quality of life (HRQoL) in all dimensions, including physical, psychological, and social dimensions.

Objective: This study was conducted to examine different factors that may be associated with functional disability and poor HRQoL, with the aim of targeting these factors in the future to improve physical activity, functional outcomes, and HRQoL.

Methods: A single-center cross-sectional study was conducted on 38 patients with SSc to compare characteristics between patients with and without disability using the Health Assessment Questionnaire Disability Index (HAQ-DI). Quality of life was assessed using the Short Form-36 (SF-36). Linear regressions were performed to examine variables contributing to functional disability.

Results: Almost 65.78% (n = 25) of patients in the study group reported functional disability. The presence of functional disability was associated with reduced HRQoL, as reflected by physical function (P = 0.0001), physical role (P = 0.016), bodily pain (P = 0.001), general health (P = 0.002), social functional (P = 0.002), emotional role (P = 0.042), and mental health (P = 0.025) domains of the SF-36 score. Multiple linear regression indicated that the main predictive factors associated with HAQ-DI were the modified Hand Mobility in Scleroderma, modified Rodnan skin score, DIstance walked in 6 minutes, BOrg dyspnea index, and SAturation of oxygen at 6 minutes (DIBOSA), and Fatigue Severity Scale among patients with SSc.

Conclusion: In patients with SSc, recognizing the relationships between clinical findings and functional disability will allow the development of further management strategies to minimize disease severity and enhance HRQoL.

Objective: This study aims to define the clinical, laboratory, and serologic characteristics of SSc patients with ILD and to present the frequency of chest computed tomography features.

Methods: Two hundred twenty-six SSc patients who applied to the Rheumatology Department between January 2007 and August 2019 were retrospectively examined. A total of 100 SSc patients with ILD (44.2%) were determined. Clinical, laboratory, and serological features of SSc patients with and without ILD were compared.

Result: Both groups had similar characteristics in terms of age and sex. The duration of disease (p=0.001) and follow-up time (p=0.001) were longer in SSc patients with ILD. Multivariable logistic regression analysis indicated that the duration of disease (OR: 1.06 (1.01-1.13), p=0.029), presence of gastrointestinal system involvement (OR: 3.29 (1.28-8.46), p=0.013) and anti-SCL70-positivity (OR: 6.04 (2.35-15.49), p <0.001) were associated with ILD. There was an inverse relationship between Anti-CENP-B positivity and the presence of ILD (p=0.001). The assessment regarding the chest computed tomography characteristics of interstitial pneumonia patterns were as follows: 82.5% non-specific interstitial pneumonia, 14.4% usual interstitial pneumonia, and 2.1% desquamative interstitial pneumonia. The most frequent abnormal findings included ground-glass opacification (88.7%), reticulation (64.9%), traction bronchiectasis (57.7%), septal thickening (52.6%) and honeycombing (28.9%).

Conclusion: We have shown a relationship between anti-SCL70, disease duration, gastrointestinal system involvement, and ILD in SSc patients.

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.]]> https://www.benthamscience.comarticle/118431 Methods: In this prospective study, 11 patients with systemic scleroderma who were referred due to aggravated Raynaud's were included. For all patients, questionnaires were filled up, and physical examination was performed separately for both treatment and control hands, and then similar volumes of botulinum toxin type A (Botox) and normal saline were randomly injected.

Results: The results showed that there was a significant difference in Raynaud's score (P = 0.001), Quick-Dash score (P = 0.01), Mc-Cabe cold score (P = 0.003), the mean frequency of recurrences arracks (P = 0.01), pain (0.005) (P = 0), skin color (P = 0.01), and duration of Raynaud's phenomenon (P = 0.006) between the intervention and control groups after two months.

Conclusion: Following Botox injection, a significant improvement in terms of various Raynaud's parameters as well as the clinical manifestations was observed in the intervention group. Together, botulinum toxin type A could retrieve the hand function, the cold sensitivity, and the painful feeling caused by Raynaud's syndrome.]]> https://www.benthamscience.comarticle/117888 Objectives: To estimate the effect of disease activity as measured by different disease activity indices on the risk of subsequent organ damage.

Methods: The European Systemic sclerosis study group activity index (EScSG AI), the European Scleroderma Trials and Research Group Activity Index (r-EUSTAR AI), 12 point activity index proposed by Minier (12point AI) were calculated for 91 patients; the CRISS (The Composite Response Index for Systemic Sclerosis) for patients included after 2016. Data were analysed by parametric and non-parametric tests and logistic regression.

Results: EscSG AI, r-EUSTAR AI and 12point AI correlated with lung involvement. EScSG AI and r-EUSTAR AI correlated with diffuse skin involvement. EscSG AI correlated with digital ulcers and diffuse cutaneous involvement and r-EUSTAR AI with a renal crisis. Bivariate analysis showed an inverse correlation between the three disease activity scores and forced vital capacity (FVC) (p<0.001) and diffusing capacity for carbon monoxide (DLCO) (p<0.001) and positive correlation with pulmonary fibrosis (p<0.001), modified Rodnan skin score (mRSS) (p<0.001), health assessment questionnaire (HAQ) (p<0.001), systolic pulmonary pressure (sPAP) (p<0.001), C-reactive protein (CRP) (p<0.001) and capillaroscopy scoring (p<0.001) at both baseline visit and the 3-year follow-up visit. Logistic regression revealed that baseline EScSG AI adjusted for gender and age and that baseline 12-point AI both adjusted and unadjusted predicted worse skin involvement at 3-year follow-up; while adjusted EScSG AI predicted decreasing DLCO. Also, 12-point AI predicted a decline of FVC and higher HAQ scores at 3-year follow up; while baseline r-EUSTAR AI was able to predict muscular deterioration, decline of FVC and the increase of HAQ score during 3 years of following. An active disease according to EScSG AI at first visit predicted progression of joint involvement while an active disease at baseline showed by r- EUSTAR AI predicted muscular deterioration, FVC and DLCO worsening, as well as an increase in HAQ score during the follow-up period. r-EUSTAR AI was the only score to predict the decrease of FVC in a multiple regression prediction model (OR= 1.306 (1.025, 1.665), p=0.31) while baseline EScSG AI best predicted worsening of DLCO (OR=1.749 (1.104, 2.772), p=0.017).

Conclusion: Our study could not establish a gold standard to assess disease activity in SSc; especially EscSG AI and r-EUSTAR AI could quantify and predict major organ involvement in daily practice. CRISS can be useful as an outcome measure for patients with short disease duration included in clinical studies.]]> https://www.benthamscience.comarticle/118204 https://www.benthamscience.comarticle/115965Background: Dermatological disorders are cutaneous infirmities which are frequently occurring and increasing at an alarming rate. These range from mild itching/redness (dermatitis) to fatal skin cancers and has posed a major health concern. Azadirachta indica A. Juss (commonly known as neem), a member of Meliaceae family, is an Indian medicinal plant which has been known for its health promoting effects since ancient times.

Objective: The review highlights the traditional practices, pharmacological aspects, and formulatory approach of neem for the treatment of dermatological disorders. Further, recent patents and novel delivery systems (developed and in pipeline) improving skin delivery and therapeutic profile of neem are discussed.

Results: Neem is a traditional medicinal plant that has been employed for the prevention and treatment of numerous ailments covering systemic and topical disorders. Scientific studies have validated the traditional claims of neem and attributed these health benefits to the presence of more than 300 structurally diverse and complex compounds. It possesses anti-inflammatory, antibacterial, analgesic, antiviral, antifungal, immunomodulatory and antioxidant activities which substantiate its use as skin therapy. Various novel formulations and associated patents that improved the permeability of neem based products across skin could be found in literature.

Conclusion: Critical appraisal of available literature revealed that neem possesses anti-microbial, anti-inflammatory, antioxidant and antiseptic properties. Thus it has the potential to be developed as a single effective therapy for the management of multimodal skin disorders. Further, pharmaceutical tailoring of neem by implication of novel carriers could enhance its penetrability across skin.

Methods: 88 patients fulfilled the criteria of RA(N:46) and SLE(N:42);using disease-modifying antirheumatic drugs or immunosuppressive, we evaluated their demographic data, co-morbid diseases, the number of medications, estimated income, having health insurance, family size and disease poor prognostic factors. The 8-item Morisky’s Medication Adherence, Depression by Beck depression inventory (21 Q), and drug literacy level were used.

Results: Medication non-adherence was seen in 91.3% of the RA group and 90.4% of the SLE group. Moderate to very severe depression was seen in [21 (45.7%)] and [12 (25.9%)] of the RA and SLE patients, respectively. In the SLE group, depression and having poor prognostic factors, and in the RA group, depression, having co-morbid diseases, and higher pill numbers had a significant effect on medication adherence.

Conclusion: There was a high prevalence of drug non-adherence in our RA and SLE patients. The most prevalent factor in non-adherence in both groups was depression. After that, in RA patients the presence of co-morbid disease and in SLE patients, the presence of poor prognostic factors were related to non-adherence. Factors like income, health insurance, disease duration, and health literacy had no significant effect on medication adherence.

Methods: The goal of the present review article is to provide information about Hutchinson- Gilford progeria syndrome (HGPS) and the use of CRISPR/Cas technology as a promising treatment approach in the treatment of the disease. The review also discusses about different pharmacological and non-pharmacological methods of treatment currently used for HGPS.

Results: The main limitation associated with progeria is the lack of a definitive cure. The existing treatment modality provides only symptomatic relief. Therefore, it is high time to develop a therapeutic method that hastens premature aging in such patients.

Conclusion: CRISPR/Cas technology is a novel gene-editing tool that allows genome editing at specific loci and is found to be a promising therapeutic approach for the treatment of genetic disorders such as HGPS where dominant-negative mutations take place.

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.

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).

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).

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.

Background: Worldwide, the rise in the prevalence of allergic diseases has continued in the industrialized world for more than 50 years. About 0.05-2% of the population is estimated to experience anaphylaxis at some point in life. Quisqualis indica Linn in an ornamental plant that has been rarely used as a herbal medicine, however, the presence of polyphenols and flavonoids have been reported to possess anti-inflammatory, antipyretic and immunomodulatory activity, which have some pathological relevance with anaphylaxis.

Objective: The objective of the present research was to investigate, scientifically explore and understand the probable anti-anaphylactic mechanism of ethanol extracts of Quisqualis indica Linn. via different preclinical models.

Materials and Methods: In-vitro study was done on de-granulated mesenteric mast cells induced by compound 48/80 and in-vivo study was done by Passive Cutaneous Anaphylaxis (PCA) model. In the in-vitro study degranulated mesenteric cells were grouped into negative control (compound 48/80 treated), positive control (Disodium cromoglycate + 48/80 treated) and 3 test groups (EEQI 10 μg/ml + 48/80 treated, EEQI 50 μg/ml + 48/80 treated and EEQI 100 μg/ml + 48/80 treated). The number of degranulated mast cells was counted and compared within the different treatment groups. In the in-vivo study, the rats were first grouped into negative control (vehicle only), positive control (Disodium cromoglycate) and 2 test groups (EEQI: 100 and 200 mg/kilogram). The animals were pretreated for 12 days. On the 12th day, all the rats were immunized with serum anti-ovalbumin (obtained from an already sensitized rat) by the intradermal route. After 24 h of serum injection, Evans blue dye containing oval albumin was administered intravenously in all groups. Three days later, the rats were taken down for the severity of the anaphylactic reactions.

Results: EEQI significantly attenuates mast cell degranulation and maintains cell intactness as compared to control (P < 0.001). It was set up to support the degree of anaphylaxis as compared to the control group (P < 0.001).

Conclusion: The outcomes of the work revealed the preventive effect of Quisqualis indica Linn. against allergic manifestations.

Methods: A total of 60 CA (mean age 51.72±17.02 years, male=38), and 38 of UA (mean age=53.55±11.90 years, male=17) were recruited. The level of control was defined according to (Global Initiative for Asthma) GINA 2016 criteria. The mRNA expression of HDAC2 and P-gp was studied by quantitative real-time Polymerase Chain Reaction (PCR), the functional activity of P-gp was evaluated by a commercially available kit via flow cytometry, and HDAC2 enzymatic activity was measured by commercially available kit by Enzyme-Linked Immunosorbent Assay (ELISA).

Results: P-gp expression and the functionality were significantly higher in the UA group of patients as compared to the CA group of patients (p<0.005), moreover HDAC2 expression was significantly reduced in UA patients as compared to CA patients, (p<0.005). The enzymatic activity of HDAC2 was also significantly reduced in UA patients as compared to CA patients (p<0.005).

Conclusion: P-gp overexpression and HDAC2 under expression play an essential role in uncontrolled asthma by impairing the response to corticosteroid.

Objective: We used this compound to investigate the role of autophagy in dermal ECM protein synthesis.

Methods: Normal human dermal fibroblasts (NHDFs) were treated with 3-MA for 24 h, and mRNA encoding several ECM proteins was analyzed in addition to the protein expression of procollagen-1 and fibronectin. Several phosphoinositide 3-kinase (PI3K) inhibitors, an additional autophagy inhibitor, and small interfering RNA (siRNA) targeting autophagy-related genes were additionally used to confirm the role of autophagy in ECM synthesis.

Results: Only 3-MA, but not other chemical compounds or autophagy-related genetargeting siRNA, inhibited the transcription of procollagen-1 and fibronectin-encoding genes. Further, 3-MA did not affect the activation of regulatory Smads, but inhibited the interaction between Smad3 with p300. Moreover, 3-MA treatment increased the phosphorylation of cAMP response element-binding protein (CREB); however, CREB knock-down did not recover 3-MA-induced procollagen-1 and fibronectin downregulation.

Conclusion: We revealed that 3-MA might inhibit procollagen-1 and fibronectin synthesis in an autophagy-independent manner by interfering with the binding between Smad3 and p300. Therefore, 3-MA could be a candidate for the treatment of diseases associated with the accumulation of ECM proteins.]]> https://www.benthamscience.comarticle/102731 Objective: To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity by means of introducing aminoacyl groups.

Objective: We aimed to describe the current knowledge and clinical relevance of NO parameters in different pulmonary diseases.

Methods: We conducted a systematic literature search to identify publications reporting NO parameters in subjects with pulmonary or systemic diseases affecting the respiratory tract. A narrative review was created for those with clinical relevance.

Results: Estimation of pulmonary NO parameters allows for differentiation between central and peripheral inflammation and a more precise analysis of central airway NO output. C_ANO seems to be a promising marker of parenchymal inflammation in interstitial lung diseases and also a marker of tissue damage and altered gas diffusion in chronic obstructive pulmonary disease and systemic diseases affecting the lung. In asthma, C_ANO can detect small airway involvement left undetected by ordinary FENO measurement. Additionally, C_awNO and D_awNO can be used in asthma to assess if FENO is increased due to enhanced inflammatory activity (increased C_awNO) or tissue changes related to bronchial remodelling (altered D_awNO).

Conclusion: NO parameters may be useful for diagnosis, prediction of disease progression and prediction of treatment responses in different parenchymal lung and airway diseases. Formal trials to test the added clinical value of NO parameters are needed.

Objective: This study aims to investigate the antitumor effect and the mechanism of growth modulation of gastric cancer cells by TSA.

Methods: The cell proliferation of gastric cancer cells was measured by MTT and BrdU immunofluorescence assays. Soft agar assay was used to detect the colony formation ability of gastric cancer cells. Flow cytometry was used to examine cell cycle and apoptosis. Western blot was employed to detect protein expression of target factors.

Results: TSA inhibits the proliferation of MKN-45 and SGC-7901 cells and leads to significant repression of colony number and size. Flow cytometry assays show TSA induces cell cycle arrest at G1 phase and apoptosis, and TSA effects the expression of related factors in the mitochondrial apoptotic signalling and cell cycle-related regulatory pathways. Furthermore, TSA increased histone H3K27 acetylation and downregulated the expression of PI3K and p-AKT.

Conclusion: Downregulating PI3K/AKT pathway activation is involved in TSA-mediated proliferation inhibition of gastric cancer.

Patients with APS have endothelial dysfunction, accelerated endothelial proliferation and intimal hyperplasia, atherogenesis, platelet activation, inflammatory products secretion and coagulation-fibrinolytic dysregulation. Cardiovascular complications include accelerated atherosclerosis, acute coronary syndrome, Libman-Sacks endocarditis, cardiomyopathy and venous, arterial or intracardiac thrombi. Moreover, pulmonary hypertension and peripheral microvascular dysfunction are common findings.

Management of these patients is not well documented. The role of primary thrombosis prevention remains controversial in individuals with positive antiphospholipid antibodies. Treatment of traditional cardiovascular risk factors according to current guidelines for the prevention of cardiovascular disease in the general population is recommended for primary prevention of APS. Anticoagulation therapy with unfractionated or low-molecular-weight heparin overlapped with a vitamin K antagonist remains the mainstay of the treatment for APS patients with venous thrombosis, whereas direct oral anticoagulants are not yet recommended. Data are scarce regarding the secondary arterial thrombosis prevention and it is not clear whether dual or triple antithrombotic therapy is necessary. To date, it is recommended to follow current guidelines for the management of acute coronary syndrome in the general population. New treatment targets are promising options for patients with catastrophic APS.

Objective: This study aimed to explore the effect of mannitol on spinal cord edema after SCI in rats.

Methods: Seventy-eight adult female rats were assigned to three groups randomly: a sham control group (n = 18), a contusion and normal saline contrast group (n=30), and a contusion and mannitol treatment group (n=30). We used the open-field test to estimate the functional recovery of rats weekly. Spinal cord water content was measured to determine the spinal cord edema. The ultrastructure features of the injured dorsolateral spinal cord were determined on the 7th day after SCI by HE staining.

Results: The mannitol group had greatly improved Basso-Beattie-Bresnahan (BBB) scores when compared with the saline contrast group. The spinal cord water content was increased significantly after SCI, and there was no significant difference in the water content between the NaCl and mannitol groups 1 day after SCI. The water content at 3 and 7 days after SCI was significantly lower in the mannitol group than in the NaCl group (p < 0.05). Mannitol can reduce spinal cord edema by increasing the number of red blood cells in the injured spinal cord and decrease the ratio (dorsoventral diameter/ mediolateral diameter) of spinal cord 7 days post-SCI.

Conclusion: Mannitol increases recovery of motor function in rats, reduces spinal cord edema and increases the number of red blood cells in the injured spinal cord, decreasing the ratio of spinal cord to reduce pressure.

Objective: As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial.

Methods: The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality.

Results: MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed.

Conclusion: There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

Objective: We assessed the clinical effect of NAC on the pulmonary function test of patients with diffuse scleroderma.

Methods: This study is a randomized double-blind clinical trial that was done on 25 patients with diffuse SSc without lung involvement on primary chest high-resolution computed tomography. Placebo was administered for 13 patients and 1200 milligram NAC for 12 patients. Body plethysmography parameters were assessed at the beginning of the study and after 24 weeks.

Results: Patients in the two groups were matched in the basic demographic data like age, duration of disease, and modified Rodnan skin score. The analysis showed no significant differences in parameters of plethysmography between the two groups. After importing the data of 2 patients in the placebo-treated group, who developed interstitial lung disease, DLCO in the placebo-treated group was 90.69 ± 21.29 milliliter at the end of the study, which significantly decreased compared with the beginning of the study (102.30 ± 13.83 ml). Also, changes of DLCO between the two groups were significantly different.

Conclusion: In this trial, the sensitivity of DLCO as the first marker in the evaluation of pulmonary function in patients with SSc was confirmed. On the other hand, NAC had no effect versus placebo in a period of 24 weeks.

Objectives: The present study investigated selenemia in hemodialysis patients of the ABC region of São Paulo and aimed to establish the correlation between an inflammatory marker and selenemia in this conditions disease.

Methods: This is an observational cross-sectional study of the Faculdade de Medicina do ABC in patients submitted to hemodialysis three times a week for at least six months. The eligible group composed of 21 patients, who filled out forms and underwent biochemical tests (colorimetric enzyme methods, flow cytometer, turbidimetric method and mass spectrometry).

Results: The study population showed, women (70%), men (30%) with a mean age of 47 ± 17 years, Caucasians (36%) and non-Caucasian (64%), hypertensive (68%), smokers (53%) and non-smokers (64%). There was a hegemonic prevalence of systolic arterial hypertension (SAH) 68.1% in relation to diabetes mellitus (DM) (50%). Pre and post hemodialysis (HD) selenemia showed statistical significance, which did not occur with Creactive protein. There was a predominance of females in our sample; the pre- and post- HD selenemia were within the normal range of the reference values; there was a statistically significant correlation between pre and post-HD selenemia; there was no correlation with statistical significance between values of pre and post-HD C-reactive protein.

Conclusion: Our data showed that there was no direct relationship between pre- and post- HD inflammation and pre- and post-HD selenemia.

Objective: In this study, two apoE-derived peptides were selected to investigate their antiinflammatory and anti-oxidative effects in streptozotocin-induced diabetic model of inflammation and oxidative stress.

Methods: The peptides were injected intraperitoneally into the streptozotocin-induced diabetic rats and their anti-inflammatory and anti-oxidative effects were evaluated by monitoring various oxidative and inflammatory markers.

Results: Administration of 4F, E5 and E8 peptides decreased the oxidative and inflammatory markers in STZ-induced diabetic rats to different extent, while had no significant effect on the other diabetic parameters (viz. total body weight of animals and increased blood glucose level). E5 peptide was found to be relatively more effective than 4F and E8 peptides in decreasing inflammation and oxidative stress.

Conclusion: E5 peptide can be developed as a potential candidate for inflammatory conditions.

Objective: To present a case with lung adenocarcinoma treated with pembrolizumab, which developed inflammatory arthritis and fasciitis.

Case Report: A 73-year-old male patient was referred to the rheumatology outpatient clinic with complaints of pain in the pretibial area, pain and swelling in both ankles joints and the right fırst metacarpophalangeal (MCP) joint. Three months ago he had diagnosed with lung adenocarcinoma and pembrolizumab was started. Locomotor system complaints were started after receiving two infusions of pembrolizumab. Physical examination revealed both ankle arthritis, mild edema in the pretibial region, tenderness in the muscles and arthritis in the right fırst MCP joint. Laboratory examinations showed mild acute phase reactants elevation. Lower extremity MRI showed diffuse edema in both gastrocnemius muscle and fascia, compatible with fasciitis. Pembrolizumab-related fasciitis and seronegative arthritis were diagnosed. Low dose corticosteroid was started and a significant regression was observed in the patient's complaints.

Conclusion: Inflammatory myositis with fasciitis and inflammatory arthritis in lower extremities appears to be a new adverse effect of pembrolizumab therapy.

Objective: To summarize the anti-cancer effects of Disulfiram through a thorough patent review.

Methods: This article reviews molecular mechanisms and recent patents of Disulfiram in cancer therapy.

Results: Several anti-cancer mechanisms of Disulfiram have been proposed, including triggering oxidative stress by the generation of reactive oxygen species, inhibition of the superoxide dismutase activity, suppression of the ubiquitin-proteasome system, and activation of the mitogen-activated protein kinase pathway. In addition, Disulfiram can reverse the resistance to chemotherapeutic drugs by inhibiting the P-glycoprotein multidrug efflux pump and suppressing the activation of NF-kB, both of which play an important role in the development of drug resistance. Furthermore, Disulfiram has been found to reduce angiogenesis because of its metal chelating properties as well as its ability to inactivate Cu/Zn superoxide dismutase and matrix metalloproteinases. Disulfiram has also been shown to inhibit the proteasomes, DNA topoisomerases, DNA methyltransferase, glutathione S-transferase P1, and O6- methylguanine DNA methyltransferase, a DNA repair protein highly expressed in brain tumors. The patents described in this review demonstrate that Disulfiram is useful as an anti-cancer drug.

Conclusion: For years the FDA-approved, well-tolerated, inexpensive, orally-administered drug Disulfiram was used in the treatment of chronic alcoholism, but it has recently demonstrated anti-cancer effects in a range of solid and hematological malignancies. Its combination with copper at clinically relevant concentrations might overcome the resistance of many anti-cancer drugs in vitro, in vivo, and in patients.

Objective: The present study aimed to evaluate the role of selenium and autoimmune rheumatic diseases.

Data Sources: PubMed, Scopus, Science Direct, and Google Scholar.

Study Eligibility Criteria: All the studies on the use of selenium without any limitations in terms of the preparation method, administration route, or formulation process were included in the study. The exclusion criteria were: 1) Articles published in languages other than English, 2) Administration of chemical and hormonal drugs rather than selenium, 3) Investigation of the effects of selenium on the autoimmune problems in animal models, and 4) Insufficiency of the presented data or poor description of the applied methods. Furthermore, review articles, meta-analyses, expert opinions, editorial letters, case reports, consensus statements, and qualitative studies were excluded from the study.

Data Extraction: In this systematic review, articles were evaluated through searching following keywords in combination with selenium: "autoimmune rheumatic diseases "or "scleroderma" or "systemic sclerosis" or "Behcet's disease" or "Sjögren syndrome" or "systemic lupus erythematosus" or "musculoskeletal diseases" or "rheumatoid arthritis" or "vasculitis" or "seronegative arthritis" or "antiphospholipid antibody syndrome".

Results: Of 312 articles, 280 were excluded and 32 articles were entered in this study. Based on the majority of studies assessing selenium level in patients with collagen vascular diseases, lower selenium levels were observed in these patients. Moreover, the majority of articles showed an improvement in clinical symptoms of collagen vascular diseases compared to controls after the treatment of patients with different dosages of L-selenomethionine.

Conclusion: A decrease in the serum level of selenium was noted in patients with autoimmune diseases, which may be a risk factor for inflammation and initiation of autoimmunity in these patients. A sufficient quantity of selenium has been shown to contribute to the management of complications of autoimmune diseases and even improved survival in patients with autoimmune diseases, which may be due to the anti-inflammatory effects of selenium. Since this issue is of clinical importance, it can be considered in potential nutrition interventions and have beneficial effects on some autoimmune diseases.

Case Presentation: A 55 years old female presented with insidious onset and progressive course of diffuse skin thickening of face, neck, arms, forearms, thighs, chest, back, and excluding both hands and feet of 6 years’ duration associated with arthralgia, dysphagia and dyspnea on exertion of 1- year duration. There was no history of Raynaud’s phenomenon. Erythrocyte sedimentation rate was 100 mm/1st h, autoantibodies for SSc were negative, nail fold capillaroscopy normal, pulmonary function tests showed restrictive pattern and high-resolution computed tomography showed interstitial lung fibrosis. Patient was not fulfilling the American collage of rheumatology/European League Against Rheumatism classification criteria for SSc. Skin biopsy was done and revealed histological appearance of scleredema. Investigations were done for disease association with scleredema. The patient was not diabetic, antistreptolysin O titer was normal, serum protein electrophoresis, immunofixation and bone marrow biopsy were done, and the patient was diagnosed as scleredema associated with immunoglobulin A kappa multiple myeloma. Treatment by combination of bortezomib, cyclophosphamide, and dexamethasone was started with marked clinical and hematological improvement.

Conclusion: Many conditions mimic SSc including scleredema, which may be the initial presentation of multiple myeloma. Rheumatologists and dermatologists should be able to recognize these conditions to provide the suitable management and follow-up for these patients.

Objective: In order to express proteins that contain di-sulfide bands, an oxidative space such as the periplasmic environment of the bacteria is required. Therefore, a leader sequence which named Signal Peptide (SP) is needed to direct recombinant protein to fold in periplasmic space. Interleukin-2 (IL-2) is a prominent cytokine which known as growth factor for T-cells and typically produced by a variety of immune cells that stimulate and regulate inflammatory and immune responses.

Methods: This study was designed to predict the best signal peptides to express IL-2 in E. coli. To predict the best signal peptides for the expression of IL-2 in Gram-negative bacteria (E. coli), forty-five sequences of SPs were extracted from data base. Some most important details such as n, h and c regions of signal peptides and their probability were studied through the signalP software.

Afterwards, physico–chemical features of SPs were analyzed by Portparam and Solpro tools. Finally, secretion-pathway and sub-cellular localization sites were evaluated by PRED-TAT and ProtcompB softwares.

Results: At the end of the in-silico analyzes, it was determined that ccmH, PelB, traU, yohN, lolA, yhcN are the most reliable SPs, respectively, with highest score and best performing to express the IL-2 protein in E. coli.]]> https://www.benthamscience.comarticle/85494

Methods: A structured search of bibliographic databases for peer-reviewed research literature revealed 139 articles including our own that are presented and critically evaluated in this TLR4-directed review.

Objective: To understand the molecular role of Toll-like receptor 4 (TLR4) as a key regulator of skin anti-microbial defense, wound healing, and cutaneous tumorigenic inflammation. The specific focus of this review is on recent published evidence suggesting that TLR4 represents a novel molecular target for skin photoprotection and cancer photochemoprevention.

Results: Cumulative experimental evidence indicates that pharmacological and genetic antagonism of TLR4 suppresses UV-induced inflammatory signaling involving the attenuation of cutaneous NF-κB and AP-1 stress signaling observable in vitro and in vivo. TLR4-directed small molecule pharmacological antagonists [including eritoran, (+)-naloxone, ST2825, and resatorvid] have now been identified as a novel class of molecular therapeutics. TLR4 antagonists are in various stages of preclinical and clinical development for the modulation of dysregulated TLR4-dependent inflammatory signaling that may also contribute to skin photodamage and photocarcinogenesis in human populations.

Conclusion: Future research should explore the skin photoprotective and photochemopreventive efficacy of topical TLR4 antagonism if employed in conjunction with other molecular strategies including sunscreens.]]> https://www.benthamscience.comarticle/93047 https://www.benthamscience.comarticle/95175 https://www.benthamscience.comarticle/89902

Reporting Case: A 35 years old woman, a known case of scleroderma underwent open-heart surgery 20 years before being diagnosed as scleroderma, presented by dyspnea especially on activity. The High Resolution CT (HRCT) for evaluating the interestial lung disease was done which detected a 7 cm (in greatest diameter) inflammatory mass in posterior aspect of left hemi thorax with a radiopaque thread in its center. True cut biopsy was done and sent for pathology, which revealed fragments of foreign body materials probably gauze pad fibers with cell debris and blood.

Conclusion: Here, we highlighted the details in clinical history, CT findings, and pathology report of gauzoma in thorax of a scleroderma patient following previous open-heart surgery. It can be guidance for clinician to consider this diagnosis in patients with past history of operation.]]> https://www.benthamscience.comarticle/89903

Objective: Since it is uncommon in children, many aspects of the disease remain discussable. With this review, we aimed to revise recent findings and new developments in this rare condition.

Method: A systematic literature research was performed, using the following medical databases: Pubmed/ Medline and the Cochrane Library. We searched for up-to-date randomized controlled studies, case-control studies, and cohort studies and cases reports on juvenile scleroderma (both systemic and localized form).

Results: Skin manifestations are most prominent features of the systemic form, followed by musculoskeletal and vascular involvement. Cardiovascular, gastrointestinal and renal disorders are rare in childhood. Combination of disease modifying anti- rheumatic drugs (methotrexate, mycophenolatemofetil, cyclosporine) and steroid reprents the first line therapy. Bosentan is used for cases with pulmonary hypertension and for extensive digital ulcerations. Biological treatment emerges as a useful treatment option in most severe form of the disease. Localized scleroderma is characterized with sclerodermatosis of the skin. Internal organ involvement is not expected. Classification of the local scleroderma is made according to the size and localization of the skin changes. There are few different therapeutical options but there is no specific therapy for the localized scleroderma.

Conclusion: Many data regarding disease features and treatment options in juvenile scleroderma are based on studies among adults. There is a striking need for multicentric, prospective studies among children with juvenile scleroderma, in order to elucidate some questions of clinical course and disease prognosis. Recent genetic studies have revealed the role of the genetic factors (namely HLA class II) in the pathogenesis of the disease. Emerging biological agents and new treatment options are showing promising results.]]> https://www.benthamscience.comarticle/83020 Methods: It was a prospective, observational, single centre study of fifty consecutive patients with SSc who presented to rheumatology clinic. Gut score was assessed using UCLA SCTC GIT 2.0 questionnaire. 35 patients underwent esophago- gastro duodenoscopy(UGIE), 31 underwent esophageal manometry, 37 underwent lactulose breath test to assess orocaecal transit time (OCTT) and glucose breath test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent gastric emptying scintigraphy to measure gastric emptying time.

Results: GI involvement was seen in 98% of patients, with most common symptom being regurgitation (78%). Mean T score of the GUT score was 0.60±0.27. In UGIE, esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis. Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure was 16.1± 12.7 mmHg with hypotensive sphincture in twelve patients. Esophageal peristaltic abnormalities were observed in 28(90%) patients. Gastric emptying was delayed in10/36 patients. OCTT was prolonged in 23/ 37 patients whereas SIBO was noted in 7/37.

Conclusion: GI involvement is common in SSc with esophagus being most commonly affected. Motility abnormalities make them prone for super added infections especially infectious esophagitis and SIBO and should be investigated for early detection and treatment.]]> https://www.benthamscience.comarticle/87944

Methods: Information was collected from previously published literatures which were represented after analysis in terms of various aspects such as principles, composition, preparation, mechanism of penetration, modified forms, characterization, marketed preparations and its applications.

Result: This review is represented in an informative and easily understandable way. Basic principles and background were covered in the introduction section. Composition section contains the basic components of formulations along with the impact of various parameters on the characterization of the ethosome. A detailed discussion of all the methods along with their own utility is elaborately provided. Various aspects of characterization studies of ethosomes are also discussed. Therapeutic and cosmetic applications of ethosomes are also outlined here.

Conclusion: In spite of having a excellent permeation-enhancing and targeted drug release profile, ethosome suffers from limited commercialization. Various challenges regarding their commercialization and product development are also discussed in this review with an objective of acting as a directional route for the researchers.]]> https://www.benthamscience.comarticle/84109 https://www.benthamscience.comarticle/84015

Objective: There are disorders that can cause hardening and tightening of skin and mimic scleroderma but are rarely associated with Raynaud phenomenon, sclerodactyly, and autoantibodies in the serum, features specific to scleroderma/systemic sclerosis.

Conclusion: These are termed as “scleroderma variants” or “scleroderma like disorders”. This review discusses the various “scleroderma variants” e.g. scleromyxedema, scleredema, nephrogenic systemic fibrosis, and eosinophilic fasciitis.]]> https://www.benthamscience.comarticle/84105

Conclusion: Because of its potential value in monitoring disease progression and treatment response, nailfold capillaroscopy may also have a role in the management of overt systemic sclerosis.

Results: Its application in scleroderma-spectrum disorders in which a microvascular component is suspected may also provide new insights into their pathophysiology.]]> https://www.benthamscience.comarticle/88595 https://www.benthamscience.comarticle/87639

Objective: This review focuses on the methods currently used to evaluate the stem cell therapies for SCI.

Results: Various kinds of stem cells involving embryonic stem cells (ESCs), bone marrow stromal cells (BMSCs), neural stem cells (NSCs) and induced pluripotent stem cells (iPSCs) are extensively used in regenerative research of SCI. For evaluation, the survival and integration of transplanted cells, spinal cord reconstruction and functional recovery all should be considered. Histological and histochemistrical, microscopic, and colorimetric assays, and real-time RT-PCR techniques are applied to determine the outcome. From the three main aspects-transplanted cells, spinal cord structure, and functional recovery-we summarize and discuss these methods with certain instances of applications in SCI models. Importantly, for the evaluations of function, neuronal transmitting, electrophysiological analysis and behavioral score are included.

Conclusion: Wider conjunction of established technologies, as well as the further development of nondestructive methods might make a big difference in testing stem cell therapies.]]>