The present study aims at analysing the frequency of calcific tendinitis in uncommon sites, in order to fill a gap in knowledge and awareness regarding non-rotator cuff calcific tendinopathy, thus avoiding improper clinical choices and helping to identify this condition.

Methods: This systematic review was conducted following the PRISMA guidelines. We performed a search on Pubmed and Scopus databases concerning atypically sited extra-rotator cuff calcific tendinopathy published since 1950.

Results: The research found a total of 267 articles and 793 non-rotator cuff cases of calcific tendinopathy registered. The spine (213 – 26.86%), foot and ankle (191 – 23.95%), and hip (175 – 22.06%) appeared to be the most common sites of calcific tendinopathy after the rotator cuff, whereas the longus colli C1-C2 (204 – 25.72%), Achilles (173 – 21.81%), and rectus femori (61 – 7.69%) were the most commonly affected tendons.

Conclusion: A better awareness of this condition in several different sites of the body than the rotator cuff could avoid unnecessary choices both in assessment and treatment.

Objective: This study aimed to authenticate the outcomes of prior research employing the HM and GEP algorithms, endeavoring to expedite the formulation of efficacious therapeutics for osteosarcoma.

Methods: A robust quantitative constitutive relationship model was engineered to prognosticate the IC₅₀ values of innovative synthetic compounds, harnessing the power of gene expression programming. A total of 39 natural products underwent optimization via heuristic methodologies within the CODESSA software, resulting in the establishment of a linear model. Subsequent to this phase, a mere quintet of descriptors was curated for the generation of non-linear models through gene expression programming.

Results: The squared correlation coefficients and s2 values derived from the heuristics stood at 0.5516 and 0.0195, respectively. Gene expression programming yielded squared correlation coefficients and mean square errors for the training set at 0.78 and 0.0085, respectively. For the test set, these values were determined to be 0.71 and 0.0121, respectively. The s2 of the heuristics for the training set was discerned to be 0.0085.

Conclusion: The analytic scrutiny of both algorithms underscores their commendable reliability in forecasting the efficacy of nascent compounds. A juxtaposition based on correlation coefficients elucidates that the GEP algorithm exhibits superior predictive prowess relative to the HM algorithm for novel synthetic compounds.

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.

Objectives: In the present study, the protective effects of vitamins E and D on renal toxicity caused by tamoxifen in female Wistar rats were investigated.

Materials and Methods: Twenty-five adult female rats weighing 180-200 were randomly divided into five groups with 5 rats. Group C, T, TE, TD, and TED were treated with olive oil, tamoxifen, tamoxifen + vitamin E, tamoxifen +vitamin D, and tamoxifen + both vitamins for four weeks. ELISA Kits measured the oxidant and antioxidant tests and TNF-α in kidney tissue. The spectrophotometric method measured urea, uric acid, and creatinine in serum and urine.

Results: Tamoxifen significantly decreased the weight of rats, GPx, CAT, SOD levels and increased TNF-α, urinary creatinine level and, serum uric acid, urea levels (P < 0.05). But, treatment with vitamin D and simultaneous administration of vitamins led to a significant decrease in the level of (TNF-α) compared to the tamoxifen group (p < 0.01). Also, the histopathology results showed that the simultaneous administration of vitamins has significantly resolved the damage caused by the use of tamoxifen.

Conclusion: The present study's findings showed that using vitamins E and D prevents kidney damage through antioxidant and anti-inflammatory effects. In addition, using vitamins E and D probably showed stronger synergistic effects against kidney damage.

This mini-review aims to substantiate the possibilities of using the cardiomarkers (CSTnI and CSTnT) to assess the prognosis of patients suffering from hypertension and to discuss potential mechanisms that cause injury to myocardial cells and increase serum levels of CSTnI and CSTnT.

This is a narrative mini-review, which was prepared using the following databases: Pubmed/Medline, PubMed Central, Embase, Scopus, and Web of Science. The following keywords were used in the literature search: “myocardial cells”, “injury”, “damage”, and “hypertension” in combination with the terms “mechanisms of injury” “predictive significance”, “cardiac troponins”, or “cardiospecific troponins”.

Objective: The objective of this review is to give a comprehensive overview on the role of micronutrients in the treatment of broad-spectrum diseases and also give insightful knowledge regarding the numerous food sources for obtaining nutrients, their dietary reference values, and their deficiencies. In this review, the authors have also highlighted the role of micronutrients in COVID- 19.

Findings: A properly balanced diet provides an acceptable amount of nutrients in the body. Deficiency and excessive nutrients in an individual’s diet may cause diseases or abnormal conditions. An improper diet may be responsible for the occurrence of deficiencies in iron, calcium, and iodine. Minerals like iron, boron, calcium, cobalt, phosphorous, and vitamins like K, E, A, D, and Riboflavin can cure and treat fatal diseases like Alzheimer’s, bone development conditions, osteoporosis, anemia, inflammatory bowel, and HIV Infections.

Conclusion: Micronutrients are essential for metabolism and tissue function. Sufficient consumption is thus required, but providing additional supplements to persons who do not require them may be detrimental. Large-scale studies of varied micronutrient dosages with accurate outcome indicators are needed to optimize intakes in different patient groups and the general population at large. In this review, the authors have highlighted the crucial role of micronutrients in health and disease.

Objectives: The main objective is to improve the bioavailability of CINH by formulating the nanostructure lipid carrier (NLC).

Methods: In this research, glyceryl monostearate (GMS), labrasol, and tween 20 were the main excipients selected for the formulation of NLC. Hot high-speed homogenization and ultra-sonication method was used for the NLC formulation of CINH. The characterization of the NLCs was done as per standard procedures. Optimization of the formulated NLC was carried out by applying Box- Behnken Design (BBD) with the help of the Design Expert software. The pharmacokinetic study was conducted to determine the improvement in the bioavailability of the CINH. The cytotoxicity study was performed by using the MTT assay method to know the cell viability.

Results: The optimized NLC formulation exhibited high drug content with a particle size of less than 200nm. A pharmacokinetic study showed 4 fold increase in oral bioavailability for the optimized NLC in comparison to the aqueous suspension of CINH. Minimum viability was determined as 94%, which indicates the safety of the incubated formulations.

Conclusion: NLC formulation has the potential to improve oral bioavailability with high drug loading and cell viability for CINH.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Case Presentations: Case 1. A 66-year-old man presented to our hospital with hyponatremia. He had low plasma levels of adrenocorticotropin and cortisol. The patient had a history of non-small cell lung cancer and had undergone 16 cycles of immunotherapy with sintilimab, a monoclonal antibody against programmed cell death protein 1 (PD1). He was diagnosed with adrenal insufficiency secondary to immunotherapy-associated hypophysitis and received a physiological dose of glucocorticoids. Upon discharge, he has prescribed a continued course of hormone replacement therapy combined with immunotherapy. Case 2. The second case profiled here involved a 58- year-old patient diagnosed with gastric antrum cancer. After ten months of immunotherapy with carrelizumab, a human high-affinity immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody drug, the patient was referred to the Endocrinology Department at our medical centre for adrenal nodules and intolerance of anorexia. He also suffered from hypophysitis and was prescribed hormone replacement therapy combined with immunotherapy.

Conclusion: This article discusses the clinical characteristics, diagnosis, treatment, and subsequent follow-up for immunotherapy-associated hypophysitis in the context of two case reports. Based on our findings and observations, we conclude that patients with immunotherapy should regularly be referred to endocrine-related follow-up during tumour treatment.

Methods: The structure-property relationship illustrates how the modification of the chemical structure influences the absorption, distribution, metabolism, excretion, and other related properties of drug compounds. Understanding the structure-property relationships of clinically approved GPCR-targeted drugs and their analogues could provide useful information on the lead-to-candidate optimization strategies.

Results: Among more than 50 GPCR antagonists and agonists approved in the last decade, the structure-property relationships of 17 drugs are compiled from medicinal chemistry literature, in which detailed pharmacokinetic and toxicological properties are disclosed not only for the final drug candidate but also for key analogues generated during the lead optimization campaign.

Conclusion: The structure-property relationships hereby summarized demonstrate how in vitro and in vivo properties of the membrane protein-targeted ligands could be effectively optimized, in many cases, without requiring a significant change in the molecular size. This information is expected to provide valuable insights to expedite new GPCR-targeted drug development.

Objective: This study aims to find the underlying active mechanism of OD against OS.

Methods: The candidate ingredients as well as drug targets of OD were obtained from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, respectively. Meanwhile, the OS diseaserelated targets were acquired from GeneCards and MalaCards online databases. Then, by using Venny 2.1, the common key targets were imported into the STRING database to acquire their interaction relationship, and imported this PPI network file (.csv) into Cytoscape 3.6.0 software and merged to obtain PPI network intersections. Meanwhile, the MCODE plugin of Cytoscape was also used to further trim the core therapeutic targets. GO and KEGG enrichment and molecular docking analyses were performed to predict the underlying mechanism of OD against OS. Furthermore, in silico analysis results were validated by a series of cellular functional and molecular biological assays.

Results: A total of 131 putative targets were identified to be involved in the anti-OS activity of OD. The PPI network, GO as well as KEGG analyses revealed that the 18 core targets were closely related to cell proliferation, apoptosis. Importantly, the subsequent in vitro assays verified that the suppressive effect of OD on OS cell growth indeed resulted from disrupted apoptosis and cell proliferation via Akt and ERK signaling pathways. Furthermore, our results showed that quercetin, beta-sitosterol and 2-methoxy-3- methyl-9,10-anthraquinone were the key ingredients, while PTGS2, CASP3 and JUN were the key targets in delivering the pharmacological activities of OD against OS, thus providing an insight into the anti-OS action of OD from a holistic perspective.

Conclusion: In summary, our results indicate that OD has good prospects in the treatment of OS.

When examining previous publications, most do not cover aminopeptidases and their role in cancer processes. Aminopeptidases play a vital role in cell processes and functions; however, their overexpression may lead to a rapid proliferation of tumor cells. Emerging evidence supports the rationale of leveraging aminopeptidase activity as a targeted approach for new oncological treatments. This article specifically looks at the biological role of aminopeptidases in both normal and cancer processes, and their potential as a biological target for future therapeutic strategies.

Objective: This study aimed to illuminate the in vivo usefulness of nanotechnology as a treatment for osteoporosis via analyzing the effectiveness of nano-hydroxyapatite (nHa), nano-hydroxyapatite/ chitosan (nHa/C), and nano-hydroxyapatite/silver (nHa/S) in mitigation of osteoporosis in ovariectomized rats.

Methods: The characterization of the nHa, nHa/C, and nHa/S was carried out using TEM, SEM, FTIR, and Zeta potential measurements. This in vivo study included 48 adult female rats that were randomized into six groups (8 rats/group): (1) Sham-operated control, (2) osteoporotic, (3) nHa, (4) nHa/C, (5) nHa/S, and (6) Fosamax®. Serum osterix level was quantified using ELISA. Femur bone morphogenetic protein 2 and SMAD1 mRNA levels were evaluated by qPCR. The femur bones were scanned by DEXA for measurement of bone mineral density and bone mineral content. In addition, a histopathological examination of femur bones was performed.

Results: The present approach denoted that the treatment with nHa, nHa/C, or nHa/S yields a significant rise in serum level of osterix and mRNA levels of bone morphogenetic protein 2 and SMAD1 as well as significant enhancements of bone tissue minerals.

Conclusion: The findings affirmed the potency of nHa, nHa/C, and nHa/S as auspicious nanoplatforms for repairing bone defects in the osteoporotic rat model. The positive effect of the inspected nanoformulations arose from bone formation indicators in serum and tissue, and additionally, the reinforcement of bone density and content, which were verified by the histopathological description of bone tissue sections.

Methods: Authors searched PubMed/MEDLINE, ISI-web of knowledge, and Google scholar databases for medical subject headings terms and free-text words related to the classes mentioned above of chemicals and bone metabolism and remodeling for better clarifying and understanding the main mechanisms of bone disruption.

Results: Several EDCs act as xeno-estrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties.

Discussion: Much evidence about bone disruptors was obtained from in vitro studies or animal models with equivocal results. Besides, a few data have been acquired from humans, and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, humans may be exposed to a mixture of EDCs, and the final effect on bone metabolism might be attributable to either synergistic or antagonist effects. Age of first exposure, cumulative exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other essential variables influencing bone metabolism's final effect.

Conclusion: Given these variables, observational studies are needed to analyze this issue for ecological purposes better and preserve bone health.

Methods: In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript.

Conclusion: The deficiency of vitamins in the body causes various neurological disorders like Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer’s disease, there is a lack of vitamin- B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson’s disease, vitamin- D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, vitamin-C and vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

Methods: We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.

Results: We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.

Conclusion: Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.

Materials and Methods: In this study, patients in the UA group (hyperuricaemia combined with femoral neck fracture) and the control group (normal uricaemia combined with femoral neck fracture) were selected according to the inclusion criteria. Total protein was extracted from the femoral neck of each patient. Fluorescence differential gel electrophoresis was used to separate the total proteins, and the differentially expressed protein spots were detected by image analysis. After enzyme digestion, peptide mass fingerprinting and database searches were performed to identify the differentially expressed proteins. DAVID software and Kyoto Encyclopedia of Genes and Genomes (KEGG) data were used for enrichment analysis of the screened differential proteins.

Results: After mass spectrometry and database searching, 66 differentially expressed protein spots were identified between the UA group and the control group. Most differentially expressed proteins functioned in cytoskeleton formation, energy metabolism, or signal transduction. They were mainly involved in 50 biological processes, including peroxisome proliferator-activated receptor (PPAR) signalling and fatty acid metabolism. PPARγ and PLIN1 were subject to Western blotting analysis detection; results were consistent with the Label-Free result.

Conclusion: Based on an analysis of the biological information, these proteins may be associated with the incidence and progression of the femoral neck bone tissues of hyperuricaemia patients.]]> https://www.benthamscience.comarticle/115194 https://www.benthamscience.comarticle/114590 https://www.benthamscience.comarticle/117115 https://www.benthamscience.comarticle/112827Background: The existence of a link between Graves’ Disease (GD) and Thyroid Cancer (TC) has long been investigated, however a clear pathogenic correlation is yet to be found.

Objective: We verified the presence of TC in patients submitted to surgery for GD, both with and without thyroid nodules (TN).

Methods: In this study we analyzed retrospectively a cohort of 151 patients treated at our clinic with total thyroidectomy between 2013 and 2018. All the patients were symptomatic at the time of surgery, preoperatively ultrasonographic (US) study was performed to evaluate the presence of nodules and their distribution. All patients reached euthyroid state before surgery.

Results: Nodules were detected in 53% of cases, above 60 years of age, at least one nodule was found; however, younger patients were mostly nodules free. Bilateral diffusion of nodules appeared with increasing age. Cancer was found in 19 of 151 subjects (12.5%), all were papillary carcinomas, and among them 93% were microcarcinomas. Among cancer-proven patients, 14 had thyroid nodules while 5 were nodule-free. During the follow up period, no cancer recurrence was recorded. The most common complication after surgery was transient hypocalcemia (36%).

Conclusions: Graves’ patients are burdened by major incidence of TC in the context of their TN. Pre-operative assessment in GD patients should consider the risk of cancer, US scan can help in rapid evaluation of nodules and new rising frontiers in molecular biomarkers analysis may help defining pathogenic basis of Graves’ neoplastic development.

Purpose: The purpose of this study is to evaluate the sonoelastographic findings of IET in pediatric population.

Methods: Twelve children who had been examined with ultrasound (US) and strain elastography between December 2012 and December 2019 were included in this retrospective study. The patients’ demographics and ultrasonographic findings, including the location, margin, shape, diameters, volume, structure, vascularity, and elastography values of the lesions were evaluated.

Results: Twelve lesions were detected in 12 asymptomatic patients (3 females and 9 males) with a mean age of 4.67 ± 2.27 years. The most common location of the IET was in posterior part and middle third of thyroid, and the most common appearance on US was a well-defined, ovoid-shaped, and predominantly hypoechoic solid lesion with punctate/linear branching hyperechogenities. The lesions were mostly hypovascular on Doppler US. The mean strain ratio on elastography was found to be 1.10 ± 0.04. In the follow-up of 7 patients with available information, there was no significant change in size or appearance of IET on US.

Conclusion: IET should be considered in the differential diagnosis of the lesions within the thyroid. The first step to accurately diagnose an IET is to consider it in the differential diagnosis. In addition to US, strain elastography findings can be used to distinguish IETs from papillary thyroid cancers which can have similar US appearance, and help avoid unnecessary biopsies.

Methods: Nine Corriedale sheep that had been monitored for 10 minutes during a basal stage underwent 5-minute myocardial ischemia, followed by 60-minute reperfusion. Seven of them were subjected to an induced heart failure through an overdose of halothane, two of which were treated with intra-aortic counterpulsation during the reperfusion stage. The remaining two animals were monitored during their ischemia-reperfusion stage.

Results: Data obtained in the 5 animals suffering from heart failure followed by myocardial ischemia showed that: a) heart failure induction determined decrease in cardiac output, cardiac index and systolic and diastolic aortic pressure (AoP) with respect to their basal values (p<0.05), b) myocardial ischemia decreased the WTF compared with basal and induced heart failure values (p<0.05), c) during the reperfusion stage accompanied by induced heart failure, WTF increased with respect to values observed during the ischemia induction stage (p<0.05); nevertheless, basal values were not recovered after reperfusion (p<0.05). During this 60-minute stage, systolic and diastolic AoP values were lower (p<0.05) than those at the basal stage.

Conclusion: AIx and WTF values calculated from synchronically recorded values of aortic pressure and left ventricular wall thickness during the reperfusion stage in all animals (n = 9) showed a negative correlation (p<0.05). Analysed data provided evidence of a negative relationship between a left ventricular index of myocardial function and an arterial index obtained from AoP waves.

Objective: The aim of this review is to provide the till date information regarding local and circulatory disorders, role of different vitamins and herbs on heart diseases.

Methods: This review article contains a detailed survey of literature about cardiovascular diseases, which was available in different online databases such as; PubMed, Web of Science, Science Direct, Elsevier, and Google Scholar, etc. In this review, the authors have focused on the description of cardiovascular disorders, their pathophysiological properties and importance of micronutrients, vitamins and herbs in the management of cardiovascular diseases.

Results: Cardiovascular diseases are considered responsible for approximately 17.9 million deaths annually at the global level. Surprisingly, low- and middle-income countries count for 75% of CVD deaths. These diseases represent disorders related to circulatory systems specially heart and coronary arteries. Many lifestyle associated factors such as; high cholesterol consumption, smoking, alcohol consumption, tobacco use, metabolic disorders, stress, and other factors such as; family history, age, gender and genetic factors, etc. have been found involved in occurrence of CVDs. That’s why management of diet, management of tobacco and alcohol consumption, management of stress, increased physical activities are considered population-wide strategies for control cardiovascular diseases. On the basis of pathophysiology, heart diseases are of many types and out of them, Acute Myocardial Infarction (AMI) and Sudden Cardiac Death (SCD) are considered serious and catastrophic cardiac disorders. Intake of vitamins, micronutrients, lycopene, omega 3 fatty acid and many herbs like Crataegus oxyacantha (Hawthron), Allium sativum (garlic), Salvia miltiorrhiza (Danshen), Ganoderma lucidum (lingzhi), Ginkgo biloba have been identified good for cardiovascular diseases management and treatment.

Conclusion: Cardiovascular diseases are considered one of the fatal clinical conditions, as many of them are asymptomatic. The regulation of diet, increased physical activities, and healthy lifestyle are recommended to control the development of cardiovascular problems. Including this, scientific studies have supported the role of many vitamins, nutrients and herbs as beneficial in cardiovascular diseases, but many of them could not demonstrate their role at clinical level but it is suggested that their role as nutrients can not be ignored and their consumption may reduce the cardiovascular risks.

Methods: The PRP/PPP was prepared from healthy donors using manual stepwise centrifugation and phase separation. The viability of the cells treated with gradient PRP/PPP concentrations (2, 5, 10, and 15%) was measured by the MTT assay. The YKL-40 mRNA and protein levels were assessed using qRT-PCR and western blotting. The data were compared to FBS-treated cells.

Results: Our findings revealed that the cells treated by PRP/PPP not only were morphologically comparable to those treated by FBS but also showed greater viability at the concentrations of 10 and 15%. Moreover, it was shown that PRP/PPP induce cell culture support, at least in part, via inducing YKL-40 expression at both mRNA and protein levels in a time- and dose-dependent manner.

Conclusion: Collectively, by showing cell culture support comparable to FBS, the PRP/PPP might be used as good candidates to supplement the cancer cell culture and overcome concerns regarding the use of FBS as a non-human source in human cancer research.

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.

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.

Discussion: This review will focus on these issues, critically discussing experiments and results of matrix effects in LC-MS/MS applications on catecholamine analysis in various biological matrices. Moreover, it can guide the performance of studies on matrix effects in LC-MS/MS procedures in bioanalytical systems.

Conclusion: This article is useful for academics such as analytical chemists, pharmacologists and also members of the pharmaceutical industry working on catecholamines and liquid chromatographymass spectrometry.

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.

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.

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.

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.

Methods: A systematic review of the literature in the PubMed/Medline database was performed. Articles reporting randomized clinical trials, prospective, and retrospective studies that compared the use of carbon nanoparticles in one group of patients with a control-blank group were included. The article was reported in accordance with PRISMA guidelines (CRD42021243015).

Results: The search strategy retrieved 22 studies of the literature. Fourteen studies calculated a greater number of lymph nodes detected/dissected in the central neck zone to the patients using CN solution and 1 article noted a higher rate of lymph nodes resected in the lateral neck zone in the same group of patients. A significant increase in the number of metastatic lymph nodes retrieved in the CN group was found in 7 studies. Twenty-one studies suggested that the use of CNs for the protection of the parathyroid glands was beneficial. Transient hypoparathyroidism and transient hypocalcemia were presented with a significantly lower incidence in the CN group in 13 and in 8 studies, respectively.

Conclusion: Carbon nanoparticles may improve both central and lateral neck dissection and enhance parathyroid gland identification and preservation.

Materials and methods: We reviewed the literature regarding the aggressive presentation of synchronous thyroid and breast cancer. In the current paper, we report the case of a 59 years-old woman, diagnosed with invasive ductal breast carcinoma and papillary thyroid carcinoma, presenting a natural history of both aggressive synchronous tumors. At the moment of hospitalization, the diagnosis was breast carcinoma with multiple secondary lesions, suggestive of lung and bone metastases, and nodular goiter.

Results: Searching the literature in PUBMED with the terms “thyroid carcinoma and synchronous breast carcinoma, we found 86 studies; introducing the term “aggressive,” the result included 4 studies, among which, none showed to be relevant to the terms aggressive and synchronous. A similar search was done in SCOPUS finding 92 documents and after introducing the term aggressive, the number of papers was 8, none including the literature on synchronous aggressive metastatic thyroid and breast carcinoma. A majority of imaging diagnostic tools were used in this particular medical case in order to ensure the best potential outcome. The final diagnosis was papillary thyroid carcinoma with lung and unusual multiple bone metastases and synchronous invasive ductal breast carcinoma with subcutaneous metastases.

Conclusion: The case illustrates the challenges in the correct assessment of oncologic patients, despite the advances in medical imaging and technologies and underlines the essential role of nuclear medicine procedures in the diagnostic and therapy protocols.

Methods: We designed a new prototype of gamma-probe, the Gonioprobe, and tested its clinical utility in the operating room. Gonioprobe, thanks to its 5 scintillating independent crystals, performs the dual function of Navigator and Lock-on-target. These characteristics allow the immediate guidance of the surgeon’s hand towards the source with very high precision, and with a much higher spatial resolution than commercial probes. Gonioprobe was used during intervention to detect abnormal parathyroid tissue, and to ensure no radioactivity in surgery bed after adenoma removal.

Results: We tested our gamma-probe on parathyroid adenomas particularly difficult to identify at a visual inspection due to anatomy modifications from previous neck surgery and/or characterized by uncommon localization. Moreover, parathyroid adenomas were hardly removable due to the proximity to the esophagus, neck vessels and/or recurrent laryngeal nerve (RLN). An intraoperative nerve monitoring system was used to protect the recurrent laryngeal nerve from injuries. Parathyroid hormone (PTH) assay and frozen biopsy confirmed the successful excision of the adenomas.

Conclusion: The intraoperative use of the innovative Gonioprobe along with the nerve monitoring system allowed an accurate and safe removal of parathyroid adenomas and offered a significant advantage by reducing surgical time and postoperative complications, as well as hospitalization and costs.

Methods: We searched PubMed for publications from 1 January 1980 to 1 February 2020 to identify relevant and recent literature, summarizing evaluation and the prospect of alcoholic osteopenia. Detailed search terms were ‘alcohol’, ‘alcoholic osteoporosis’, ‘alcoholic osteopenia’ ‘immune’, ‘osteoimmunology’, ‘bone remodeling’, ‘osteoporosis treatment’ and ‘osteoporosis therapy’.

Results: A total of 135 papers are included in the review. About 60 papers described the mechanisms of alcohol involved in bone remodeling. Some papers were focused on the pathogenesis of alcohol on bone through osteoimmune mechanisms.

Conclusion: There is a complex network of signals between alcohol and bone remodeling and intercellular communication of osteoimmune may be a potential mechanism for alcoholic bone. Studying the osteoimmune mechanism is critical for drug development specific to the alcoholic bone disorder.

Objective: To estimate finger doses on radiographers at a South African tertiary hospital.

Methods: Adhesive tape was used to securely fix a calibrated thermoluminescent dosimeter (TLD) on fingertips and bases of ring and index fingers of both hands of five radiographers who prepared and administered technetium-99m labelled radiopharmaceuticals. Rubber gloves were worn to avoid TLD contamination. TLDs doses were read with a Harsaw TLD Reader (Model 3500) after a week.

Results: Five radiographers prepared and administered technitium-99m labelled radiopharmaceuticals (activity range; 78.20 GBq - 132.78 GBq during a one-week measurement period). A radiographer handling 132.78 GBq received 4.74±0.52 mSv on both hands; 5.52, 4.55, 5.11 and 4.60 mSv on the fingertip of the index finger of the dominant hand (FIDH), fingertip of the ring finger of the dominant hand (FRDH), fingertip of the index finger of the non-dominant hand (FINDH) and fingertip of the ring finger of the non-dominant hand (FRNDH), respectively. The respective doses received on the finger bases were 4.50 mSv, 4.60, 4.21 and 3.48 mSv. The radiographer handling 78.20 GBq received 0.85±0.18 mSv on both hands, 1.04, 1.17, 0.77 and 1 mSv for the FIDH, FRDH, FINDH and FRNDH, respectively, while respective doses for the bases were 0.8, 0.9, 0.6 and 0.8 mSv.

Conclusion: The extremity exposures were below the annual limit (500 mSv). However, the use of syringe shields could still reduce the finger doses further.

Review of the Literature: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg.

Conclusion: The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison’s disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.]]> https://www.benthamscience.comarticle/108640 Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive patients with diabetes mellitus 1 (DM1) patients by 24-hour ambulatory blood pressure monitoring (ABPM).

Methods: We performed a clinical trial including 35 DM1 normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation.

Results: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relationship between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05).

Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive DM1 patients.]]> https://www.benthamscience.comarticle/111220 https://www.benthamscience.comarticle/110628Background: The fibroblast growth factor (FGF) family is comprised of 23 highly regulated monomeric proteins that regulate a plethora of developmental and pathophysiological processes, including tissue repair, wound healing, angiogenesis, and embryonic development. Binding of FGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan, heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediate induction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, and STAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification, FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions. Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis, and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiological changes.

Objective: This comprehensive review will discuss the biology, chemistry, and functions of FGFs, and its current applications toward wound healing, diabetes, repair and regeneration of tissues, and fatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFR and aid in mitigating various disorders, such as cancer, are also discussed in detail.

Conclusion: Inhibitors of FGFR signaling are promising drugs in the treatment of several types of cancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activation of other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activity on FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFR targeting therapies is the recent focus of several preclinical and clinical studies.

Methods: The study enrolled 22 uncomplicated overweight and obese subjects. Several parameters were examined before and after 6 weeks of a low-carbohydrate diet, enriched with 18 g of whey proteins. Anthropometric (body mass index, waist circumference) variables, fasting hormones (insulin, TSH, FT3, FT4), and metabolic (glucose, prealbumin, and lipid levels) parameters were measured. 25- OH-vitamin D (25 (OH) D), parathyroid hormone (PTH) and osteocalcin, were also quantified. Body composition parameters (fat mass, fat-free mass, body cell mass, total body water) were measured by electrical bioimpedance analysis. As cardiovascular parameters, blood pressure, endothelium flowmediated dilation (FMD), and common carotid artery intima-media thickness were also measured.

Results: The low-carbohydrate diet integrated with proteins induced a significant decrease in body weight (P < 0.001), waist circumference (P < 0.001), fat mass (P < 0.001), diastolic blood pressure (P < 0.01), triglycerides (P < 0.001), total cholesterol (P < 0.001), pre-albumin (P < 0.001), insulin (P < 0.001), HOMAIR (P < 0.001), FT3 (P < 0.05), and c-IMT (P < 0.001), and a significant increase in FMD (P < 0.001) and 25 (OH) D (P < 0.001) was also observed.

Conclusion: All these results suggest that a short-term non-prescriptive low carbohydrate diet, enriched with whey proteins, may be a good way to start losing fat mass and increase health.

Methods: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats’ cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively.

Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor.

Conclusion: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Methods: A total of 81 TM patients, including 56 females and 25 males, with a mean age of 27.5± 6.8 years, were enrolled consecutively. Serum levels of vitamin D and other biomedical parameters were measured. Then, all patients were subjected to TD echocardiography. Correlations between the serum parameters and systolic and diastolic indices were examined.

Results: The serum level of vitamin D was correlated with systolic and diastolic indices such as the EF (r= 0.33, P= 0.003) and TD Imaging (TDI)-lateral (r= 0.31, P= 0.005). However, no correlations were observed between vitamin D deficiency and the LV septal and posterior wall thickness, TDIseptal, tricuspid regurgitation peak gradient (TRPG), pulmonary artery systolic pressure (PASP), deceleration time (DT), and propagation velocity (PVcm/s) indices. The results revealed also no linear correlations between serum vitamin D and albumin (r= -0.17, P= 0.06), ALP (r= -0.12, P= 0.14), T4 (r= -0.11, P= 0.16), as well as TSH (r= -0.10, P= 0.19).

Conclusion: It seems that vitamin D deficiency in patients with TM is associated with systolic but not diastolic dysfunctions, possibly as consequences of related biochemical abnormalities.

Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real-time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage.

Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21).

Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

Methods：We searched PubMed for publications from 1 January 1980 to 1 January 2018 to identify relevant and latest literatures, evaluation and prospect of osteoporosis medication were summarized. Detailed search terms were ‘osteoporosis’, ‘osteocyte’, ‘osteoblast’, ‘osteoclast’, ‘bone remodeling’, ‘chondrocyte’, ‘osteoporosis treatment’, ‘osteoporosis therapy’, ‘bisphosphonates’, ‘denosumab’, ‘Selective Estrogen Receptor Modulator (SERM)’, ‘PTH’, ‘romosozumab’, ‘dkk-1 antagonist’, ‘strontium ranelate’.

Results：A total of 170 papers were included in the review. About 80 papers described bone cell interactions involved in bone remodeling. The remaining papers were focused on the novel advanced and new horizons in osteoporosis therapies.

Conclusion：There exists a complex signal network among bone cells involved in bone remodeling. The disorder of cell-cell communications may be the underlying mechanism of osteoporosis. Current anti-osteoporosis therapies are effective but accompanied by certain drawbacks simultaneously. Restoring the abnormal signal network and individualized therapy are critical for ideal drug development.

Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis.

This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.

Objective: To review the current update of the research status of chemopreventive/therapeutic molecule, Apigenin.

Methods: Compare the results of the published articles and granted patents on this compound. We also discuss the pros and cons of the present research and future direction.

Results: Cancer cells have characteristic alterations and dysregulation of various cell signaling pathways that control cell homeostasis, proliferation, motility, and survival in normal cells. Natural flavonoids are the compounds well known for their anti-inflammatory, anti-oxidant, and anti-cancerous properties. Apigenin, along with several other physiological effects, has a very low intrinsic toxicity and striking effects on the proliferation of cancer cells. Interestingly, this multitargeting molecule is getting wide acceptance among researchers. It is evident from the recent patents filed in this compound. At present, three patents have been granted only on the anticancer properties of apigenin.

Conclusion: This mini-review will explain the present research status of apigenin and will further shine some light on how apigenin performs its anti-cancerous actions by interfering with the key cellsignaling pathways.

Methods: Male C57BL/6J mice were fed with a normal diet (10% kcal as fat, lean group) or a high-fat diet (60kcal as fat, obese group) for 12 consecutive weeks. To detect the MIF expression and AMPK activation in response to I/R in isolated hearts from lean and obese mice, myocardial samples were collected from left ventricular areas at different time points. To determine whether MIF supplementation is protective against I/R injury, recombined MIF (10 ng/mL) was applied before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium staining. Western blot was used to detect myocardial MIF expression, AMPK activation and membrane glucose transporter 4 (Glut4) expression.

Results: The expression of MIF was remarkably higher in obese group compared to lean group. Ischemia increased myocardial MIF expression and phosphorylation of AMPK in lean mice, whereas it had no significant effect on obese mice. Furthermore, administration of recombinant MIF increased ischemic AMPK activation and membrane Glut4 expression in both lean and obese mice, while it reduced the infarct size in lean mice only.

Conclusion: An impaired MIF/AMPK activation response and consequent reduced membrane Glut4 expression may play an important role in increasing myocardial susceptibility to I/R in obesity.

Methods: We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented.

Result: Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis.

Discussion: Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice.

Conclusion: The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA.

Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date.

Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA.

Conclusion: We provide an overview of epigenetic modulations, particularly those involved in cancer, and discuss the recent advances in drug development that target these chromatin-modifying events, primarily focusing on novel strategies to regulate the epigenome.

Methods: This study includes three hundred ninety-five patients with large-artery atherosclerotic stroke from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and 395 age- and sex-matched healthy controls from Chinese communities. Serum MTHFR concentrations were examined and some conventional risk factors of stroke were collected. The association between serum MTHFR and large-artery atherosclerotic stroke was evaluated.

Results: A U-shaped association of serum MTHFR level with large-artery atherosclerotic stroke was observed (p for nonlinearity =0.008). After multivariate adjustment, the odds ratios (95% confidence intervals) of large-artery atherosclerotic stroke associated with the first, second, fourth, and fifth quintiles of MTHFR were 5.62 (1.10-28.87), 2.13 (0.51-8.99), 1.08 (0.21-5.56), and 2.31 (0.57-9.34), respectively, compared with the third quintiles of MTHFR. Adding MTHFR quintiles to a model containing conventional risk factors improved the predictive power for large-artery atherosclerotic stroke (continuous net reclassification improvement=63.78%, p<0.001; categorical net reclassification improvement=2.54%, p=0.012).

Conclusion: There is a significant U-shaped relationship between serum MTHFR levels and largeartery atherosclerotic stroke. Our findings raise the possibility that serum MTHFR may have a potential role in the pathogenesis of large-artery atherosclerotic stroke.

Objective: The cytostatic potential of new CP inhibitors derived from dipeptidyl nitriles is analyzed in vitro using pancreatic cancer (MIA PaCa-2) cells.

Methods: The cytotoxic and cytostatic activities were studied using MTT colorimetric assay in 2D and 3D cultures. Colony formation, migration in Boyden chamber and cell cycle analysis were applied to further study the cytostatic activity. The inhibition of cysteine proteases was evaluated with Z-FR-MCA selective substrate, and ROS evaluation was performed with DCFH-DA fluorophore. Permeability was investigated using HPLC-MS to obtain log kw. Combination therapy was also evaluated using the best compound with gemcitabine.

Results: The inhibition of intracellular CP activity by the compounds was confirmed, and the cytostatic effect was established with cell cycle retention in the G1 phase. CP inhibitors were able to reduce cell proliferation by 50% in the clonogenic assay, and the same result was achieved for the migration assay, without any cytotoxic effect. The Neq0554 inhibitor was also efficient to increase the gemcitabine potency in the combination therapy. Physicochemical properties using an artificial membrane model quantified 1.14 ≥ log Kw ≥ 0.75 for all inhibitors (also confirmed using HPLC-MS analysis) along with the identification of intra and extracellular metabolites. Finally, these dipeptidyl nitrile derivatives did not trigger the formation of reactive oxygen species, which is linked to genotoxicity.

Conclusion: Altogether, these results provide a clear and favorable picture to develop CP inhibitors in pre-clinical assays.

Patient Findings: A 56-year-old woman was referred for a 13 mm-nodular lesion of the neck incidentally discovered on ultrasound examination and mild hyperparathyroidism. A 99mTctetrofosmin/ pertechnetate subtraction scintigraphy was negative for parathyroid disease. Given the absence of suspicious ultrasound finding, a fine-needle aspiration cytology was performed with iPTH determination in the aspirate, confirming the parathyroid origin of the lesion. The patient underwent left inferior parathyroidectomy with intraoperative monitoring of iPTH and became normocalcemic. On histopathological examination, parathyroid carcinoma presenting at the resection margin was diagnosed, thus a surgery revision was requested.

Conclusion: Even if literature does not support a syndromic association between neurofibromatosis type 1 and primary hyperparathyroidism, the benefit of precociously diagnosing and treating this condition may outweigh costs associated with screening. This case report moreover demonstrates that sometimes clinical, laboratory and imaging aspects suspicious for cancer may be missing. A prompt referral to a high-volume center is crucial for the management of those cases of incidental histopathological diagnosis.

Objective: The rationale of the current study was to investigate whether this inverse association is agedependent and whether it has any role in modulating renal function and insulin resistance.

Methods: To test this hypothesis, we have carried out a hospital based study enrolling 848 subjects (558 men and 290 women) with the mean age of 50.9 ± 15.9 y. Chemiluminometric competitive immune assays were performed using commercial kits to determine 25-OH vitamin D and Parathyroid Hormone (PTH) levels. Fasting glucose levels and serum creatinine were used to evaluate diabetes and renal function.

Results: Vitamin D deficiency was predominant irrespective of age group (p = 0.21) and gender (p = 0.12). An inverse association between vitamin D and PTH was observed (r = -0.24) in middle age subjects (p = 0.02). The data segregation based on plasma vitamin D levels which were <20 ng/ml, 20.1- 30 ng/ml and >30 ng/ml confirmed the inverse association between vitamin D and PTH levels (ptrend: 0.007). Subjects with low plasma vitamin D and increased PTH exhibited elevated blood urea, serum creatinine and blood glucose. Subjects with 25-OHD deficiency showed a 3.03-folds (95% CI: 2.26- 4.07) and 2.09-fold (1.41-3.10) increased risk for diabetes and renal disease, respectively.

Conclusion: Based on the results of the present study, it is suggested that those with vitamin D deficiency need to be evaluated for possible presence of renal dysfunction, diabetes/insulin resistance in addition to assessing their PTH status.]]> https://www.benthamscience.comarticle/94290 https://www.benthamscience.comarticle/92496

Objective: This study aimed to evaluate the role of CN suspension in identifying lymph nodes and preserving the parathyroid in patients with papillary thyroid cancer (PTC).

Method: A total of 96 PTC patients were divided into a CN group (n = 46) and a control group (n = 50). All patients underwent total thyroidectomy with central lymph node dissection from 2014 to 2015.

Results: The number of lymph nodes removed in the CN group and the control group was 9.6±2.4 and 7.8±2.2, respectively, and the number of dissected lymph nodes identified as <5 mm in both groups was 4.4±1.3 and 2.4±1.4, respectively. These results were significantly different between the two groups (P < 0.05). However, the number of metastatic lymph nodes was similar in the two groups. In addition, the results further revealed that the level of serum parathyroid hormone (PTH) was significantly lower in the control group than in the CN group on postoperative day 1 and week 1 (P < 0.05), but similar outcomes were observed at postoperative month 1.

Conclusion: CN suspension plays an important role in accurately identifying lymph nodes and protecting parathyroid glands. The clinical utilization of CN suspension could increase the accuracy of surgery programs and protect parathyroid function.]]> https://www.benthamscience.comarticle/95370

Patient Findings: A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Fine-needle aspiration (FNA) on thyroid prevailing nodule did not demonstrate cellular atypia.

During follow-up, FNA was repeated on the previously analyzed nodule suspicious for Hürthle cell nodule suspicious for follicular neoplasm and on another hypoechoic right nodule which showed cellular atypia. CT was <2 pg/ml (normal values <18.2 pg/ml), anti-thyroid antibodies were positive and the patient showed a normal thyroid function.

The patient also was diagnosed with primary hyperparathyroidism with an enlarged parathyroid gland behind the right thyroid lobe. Therefore, she underwent total thyroidectomy and a selective parathyroidectomy was performed.

Histology showed an encapsulated microMTC (pT1aNxMx) associated with diffuse C-cell hyperplasia and lymphocytic thyroiditis. The neoplasm was positive for calcitonin and chromogranin A and negative for thyroglobulin. A right parathyroid adenoma was also diagnosed. One month after surgery basal and stimulated CT were <2 ng/ml. Genetic analysis did not reveal mutation of RET proto-oncogene. Twelve months after surgery, neck ultrasonography, chest and abdomen computed tomography did not demonstrated residual/recurrent disease with undetectable serum CT.

Conclusion: In the literature, few MTC cases with normal serum CT have been reported. Although MTC without elevated plasma CT is extremely rare, normal or low CT levels, do not entirely exclude this diagnosis.]]> https://www.benthamscience.comarticle/95502 https://www.benthamscience.comarticle/91258

Discussion: The areas of the body usually affected by sarcoidosis are lungs, skin, or lymph nodes; pulmonary and mediastinal involvement is seen in over of 90% of patients. Less commonly eyes, liver, heart, and brain are involved. Any organ, however, can be affected.

Early diagnosis of sarcoidosis can be difficult due to few signs and symptoms in its early stages, and when disease does occur, it may mimic other pathologies, and is made up with chest X-ray, Computed Tomography (CT)-High Resolution CT (HRCT), gallium scans. Fluoro-Deoxy Glucose– Positron Emission Tomography (FDG-PET) is another useful tool to assess the extent of disease and has a potential to evaluate the clinical management of patients responding or not to the treatment.

Conclusion: In this review, we would summarize in brief the clinical indications of PDG-PET in sarcoidosis and report the imaging features of the main organs involved in this disease.]]> https://www.benthamscience.comarticle/86555

Objective: This short review primarily discusses the most important advances in the application of the hybrids of proteins (gelatin, zein, silk fibroin,….etc) with inorganic NPs (calcium phosphate NPs, cadmium QDs, carbon nanotubes,…etc) in tissue engineering.

Results: Various strategies that have been utilized for the preparation of protein-functionalized inorganic NPs are discussed. Nanocomposite films, electrospun nanofibrous scaffolds, nanostructured colloidal composite gels and nanocomposite lyophilized sponges are among the most common platforms of protein-inorganic nanohybrid formulations used in regenerative medicine.

Conclusion: protein-inorganic nanohybrids could serve as promising platforms for different biomedical applications including bone and cartilage tissue regeneration, imaging of engineered tissues, development of antithrombogenic implant biomaterials and anti-bacterial wound dressing as well.]]>