Safety and efficacy of allogenic placental mesenchymal stem cells for treating knee osteoarthritis: a pilot study.

OBJECTIVE: Knee osteoarthritis (OA) is a common skeletal impairment that can cause many limitations in normal life activities. Stem cell therapy has been studied for decades for its regenerative potency in various diseases. We investigated the safety and efficacy of intra-articular injection of placental mesenchymal stem cells (MSCs) in knee OA healing. METHODS: In this double-blind, placebo-controlled clinical trial, 20 patients with symptomatic knee OA were randomly divided into two groups to receive intra-articular injection of either 0.5-0.6 × 108 allogenic placenta-derived MSCs or normal saline. The visual analogue scale, Knee OA Outcome Score (KOOS) questionnaire, knee flexion range of motion (ROM) and magnetic resonance arthrography were evaluated for 24 weeks post-treatment. Blood laboratory tests were performed before and 2 weeks after treatment. RESULTS: Four patients in the MSC group showed mild effusion and increased local pain, which resolved safely within 48-72 h. In 2 weeks post-injection there was no serious adverse effect and all of the laboratory test results were unchanged. Early after treatment, there was a significant knee ROM improvement and pain reduction (effect size, 1.4). Significant improvements were seen in quality of life, activity of daily living, sport/recreational activity and decreased OA symptoms in the MSC-injected group until 8 weeks (P < 0.05). These clinical improvements were also noted in 24 weeks post-treatment but were not statistically significant. Chondral thickness was improved in about 10% of the total knee joint area in the intervention group in 24 weeks (effect size, 0.3). There was no significant healing in the medial/lateral meniscus or anterior cruciate ligament. There was no internal organ impairment at 24 weeks follow-up. CONCLUSION: Single intra-articular allogenic placental MSC injection in knee OA is safe and can result in clinical improvements in 24 weeks follow-up. TRIAL REGISTRATION NUMBER: IRCT2015101823298N.

Interictal levels of calcitonin gene related peptide in gingival crevicular fluid of chronic migraine patients.

Calcitonin gene related peptide (CGRP) is a mediator of neurogenic inflammation playing a major role in the pathogenesis of migraine. Increases in serum CGRP have been detected previously in migraineurs and a return to baseline values regarded as successful treatment. As gingival crevicular fluid is known to originate from the serum, the aim of this study is to measure the CGRP content of gingival crevicular fluid (GCF) in chronic migraine patients and to determine whether there is a correlation between serum and GCF values of CGRP. For this study, 24 female individuals suffering from chronic migraine with aura were age-matched with 15 healthy individuals. Serum and GCF samples were obtained from both groups and enzyme linked immunosorbent assay performed to measure CGRP concentration. The level of CGRP in the serum and GCF of chronic migraine patients was 41 ± 16 pg/mL and 0.25 ± 0.09 pg/µg respectively while in healthy individuals CGRP levels were 29 ± 8 pg/mL and 0.19 ± 0.07 pg/µg. The correlation between CGRP levels of the GCF and serum was 0.88 for migraineurs and 0.81 in the controls. Only a weak positive relationship was observed between age and CGRP levels in both groups. CGRP levels were higher in migraineurs compared with controls both in serum and GCF. Furthermore there is a strong correlation between CGRP levels of the serum and GCF. The results of this study suggest that CGRP levels of GCF have potential diagnostic purposes in patients with chronic migraine.

Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase.

Anthrax is a deadly disease caused by Bacillus anthracis, a dangerous biological warfare agent employed for both military and terrorist purposes. A critical selective target for chemotherapy against this disease is nucleoside hydrolase (NH), an enzyme still not found in mammals. In the current study, we have performed molecular docking and dynamics studies, aiming to propose the new potent inhibitors of B. anthracis NH among National Cancer Institute (NCI) Diversity Set. We also analyzed the principal interactions of proposed compounds with the active site residues of NH and the relevant factors to biological activity. Additionally, the physic-chemical properties of free and inhibitor bound NH were evaluated and discussed. Our data showed that compound NSC79887 is a good candidate to inhibit NH and also for biological tests and further development. Also, ADMET prediction revealed that all physic-chemical parameters are within the acceptable range defined for human use.

3D protein structure prediction using Imperialist Competitive algorithm and half sphere exposure prediction.

Predicting the native structure of proteins based on half-sphere exposure and contact numbers has been studied deeply within recent years. Online predictors of these vectors and secondary structures of amino acids sequences have made it possible to design a function for the folding process. By choosing variant structures and directs for each secondary structure, a random conformation can be generated, and a potential function can then be assigned. Minimizing the potential function utilizing meta-heuristic algorithms is the final step of finding the native structure of a given amino acid sequence. In this work, Imperialist Competitive algorithm was used in order to accelerate the process of minimization. Moreover, we applied an adaptive procedure to apply revolutionary changes. Finally, we considered a more accurate tool for prediction of secondary structure. The results of the computational experiments on standard benchmark show the superiority of the new algorithm over the previous methods with similar potential function.

Evaluation of novel biomarkers for early diagnosis of bisphenol A-induced coronary artery disease.

Introduction: Bisphenol A (BPA), a ubiquitous synthetic monomer primarily used in the manufacture of polycarbonate plastic and epoxy resins and as a non-polymer additive to other plastics, can leach into the food and water supply and has been linked to cardiovascular disease (CVD). This study aimed to analyze BPA levels in patients with varying numbers of coronary artery stenosis and evaluate the prognostic value of new biomarkers cluster of differentiation 36 (CD36) and heart-type fatty acid-binding protein (H-FABP), compared to troponin I and creatine kinase (CK) MB, for detecting myocardial injury. Method: Eighty nine patients undergoing angiography at Urmia Hospital from March 2019 to 2020 were included. Serum levels of BPA, CD36, H-FABP, troponin I, and CK-M were measured. Results: When comparing CD36 and H-FABP with troponin I and CK-MB across coronary occlusion classes, receiver operating characteristic curves indicated CD36 and H-FABP had higher accuracy than troponin I and CK-MB for detecting stenosis stages. In patients with occlusion, significant alterations were detected in age, sex, BMI, hypertension, diabetes, dyslipidemia, and smoking. BPA serum concentration significantly increased compared to normal subjects. Conclusions: Our study revealed that serum biomarkers were valuable for prognosticating myocardial injury. Among these, CD36 and H-FABP were more accurate. BPA concentration correlated with myocardial necrosis, underlying disease, and occlusion stage, suggesting BPA's harmful effects.

Biochemical and molecular biomarkers: unraveling their role in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder during pregnancy, causing short- and long-term complications for both mother and baby. GDM is a multifactorial disease, and it may be affected by interactions between genetic, epigenetic, and environmental factors. However, the exact etiology is poorly understood. Despite the high prevalence of GDM, there is still debate regarding the optimal time for screening, the diagnostic threshold to apply, and the best strategies for treatment. Identifying effective strategies for therapeutic purposes as well as accurate biomarkers for prognostic and diagnostic purposes will reduce the GDM incidence and improve its management. In recent years, new biochemical and molecular biomarkers such as microRNAs, single-nucleotide polymorphisms, and DNA methylation have received great interest in the diagnosis of GDM. In this review, we discuss current and future diagnostic approaches for the detection of GDM and evaluate lifestyle and pharmacological strategies for GDM prevention.

An overview on role of nutrition on COVID-19 immunity: Accumulative review from available studies.

The novel coronavirus infection (COVID-19) conveys a serious global threat to health and economy. A common predisposing factor for development to serious progressive disease is presence of a low-grade inflammation, e.g., as seen in diabetes, metabolic syndrome, and heart failure. Micronutrient deficiencies may also contribute to the development of this state. Therefore, the aim of the present study is to explore the role of the nutrition to relieve progression of COVID-19. According PRISMA protocol, we conducted an online databases search including Scopus, PubMed, Google Scholar and web of science for published literatures in the era of COVID-19 Outbreak regarding to the status of nutrition and COVID-19 until December 2021. There were available studies (80 studies) providing direct evidence regarding the associations between the status of nutrition and COVID-19 infection. Adequate nutritional supply is essential for resistance against other viral infections and also for improvement of immune function and reduction of inflammation. Hence, it is suggested that nutritional intervention which secures an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate its course. We also recommend initiation of adequate nutritional supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority for applying this nutritive adjuvant therapy that should be started prior to administration of specific and supportive medical measures.

The relationship between thyroid function tests and sleep quality: cross-sectional study.

INTRODUCTION: The relationship between sleep and hormones have long been recognized. Studies indicated that sleep quality is one of the major modulatory effects on the endocrine system. In this study, we aimed to assess the serum concentration of thyroid hormones in individuals who suffered from low quality sleep. MATERIAL AND METHODS: Based on the Pittsburgh Sleep Quality Index and ISMA Stress questionnaire, we divided 83 participants into two groups. Forty-one individuals with low quality sleep group and 42 with good quality sleep group, all from the male students of a medical school in Tehran, Iran, participated in this descriptive and cross-sectional study. Then, serum levels of thyroid hormones including free T3, free T4, and TSH were assessed and compared between two groups. RESULTS: There were a significant increase in serum levels of FT4 (p=0.01) and TSH (p=0.02). There were also meaningful correlations between sleep score and stress score (p=0.008) as well as stress score and FT4 (p=0.03) in the case group. CONCLUSIONS: The current study showed that thyroid function tests (T4 and TSH) significantly rose in the poor sleep condition. We also found correlations between sleep score, stress score, and FT4 in the poor sleep condition group that suggest low sleep quality can affect thyroid hormones.

Saffron carotenoids change the superoxide dismutase activity in breast cancer: In vitro, in vivo and in silico studies.

Superoxide dismutase (SOD) is an important member of the antioxidant defense system and is proposed as a therapeutic agent against the ROS-mediated diseases, and a therapeutic target for cancer treatment. Saffron carotenoids, crocin (Cro) and crocetin (Crt), are antioxidants with anticancer activity. In the present study, we investigated the effects of Cro/Crt on the SOD activity in both in vivo and in vitro models of breast cancer. Both Cro and Crt showed strong radical scavenging activity and SOD inhibition in the MCF-7 breast cancer cell line. The UVVis, circular dichroism and fluorometry studies proposed the binding of both Cro and Crt with SOD; the ΔG° of binding at 310 °K was -8.6 and -4.4 kcal/mol, respectively. The docking analysis predicted the Cro/Crt binding near the active site channel, but in different sites. According to the obtained data, Cro inhibits SOD activity by scavenging superoxide radical (O2), while Crt inhibits SOD by affecting the copper-binding site. In contrast to the in vitro data, both Cro and Crt effectively increased SOD activity in breast tumors of BALB/c mice, after one month of treatment. The mechanism that is important to compensate for the SOD decreased activity in cancer.

Gummosin, a sesquiterpene coumarin from Ferula assa-foetida is preferentially cytotoxic to human breast and prostate cancer cell lines.

OBJECTIVE: The present study was conducted to find cytotoxic compounds from oleo-gum-resin of Ferula assa-foetida (asafoetida). MATERIALS AND METHODS: A dichloromethane extract of asafoetida was subjected to different chromatography analyses (including column chromatography, preparative thin layer chromatography and high performance liquid chromatography) to isolate its bioactive sesquiterpene coumarins. The structures of isolated compounds were elucidated through 1H-NMR spectra interpretation and comparison with those reported in the literature. To measure the cytotoxic activity of pure compounds, a non-fluorescent substrate called resazurin (alamarBlue®) was used in this study. Human breast and prostate cancer cell lines (MCF-7 and PC-3, respectively) and a normal human embryonic stem cell (NIH) were treated with different concentrations (50, 25, 12.5 and 6.25 µg/mL) of pure compounds. RESULTS: In this study, 10 sesquiterpene coumarins were isolated from oleo-gum-resin of F. assa-foetida and cytotoxic activity of 6 compounds was tested against MCF-7 and PC-3 cell lines and NIH cells. Badrakemin acetate (7), ferukrinone (8) and deacetyl kellerin (10) were found for the first time in the oleo-gum-resin of F. assa-foetida. Gummosin (4) showed moderate cytotoxic activity with IC50 values of 30 and 32.1 µg/mL against PC-3 and MCF-7 cell lines, respectively. None of the isolated compounds showed toxicity against NIH as a normal human cell line. CONCLUSION: The preferential cytotoxic activity of gummosin against cancer cell lines is reported for the first time in this study.

C/EBP homologous protein investigation in the serum and cerebro-spinal fluid of relapsing-remitting multiple sclerosis patients.

The exact determination of endoplasmic reticulum (ER) stress-associated proteins is not completely elucidated in the multiple sclerosis (MS) patients. We measured CHOP concentrations in the serum and cerebro-spinal fluid (CSF) of relapsing-remitting MS (RRMS) patients (n = 20) in comparison with the non-MS control group (n = 20) to determine whether this marker could be detected in the body fluids of RRMS patients. CHOP marker was not detectable in all harvested CSF samples. However, its levels were detectable in all serums harvested from both non-MS and RRMS patients and its levels in the latter group were not significantly higher than those of the non-MS control group (P value = 0.265). CHOP was not detectable in the CSF of RRMS patients in spite of the recent reports on the RRMS autopsies. Additionally, there were not any significant correlations (Spearman's correlation) between both of EDSS score and age with CHOP serum concentrations in all subjects.

Comparative study of radioprotective effects of selenium nanoparticles and sodium selenite in irradiation-induced nephropathy of mice model.

PURPOSE: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite. MATERIALS AND METHODS: Forty-five mice were divided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further subdivided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue samples were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed. RESULTS: The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite. CONCLUSIONS: Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.

Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis.

BACKGROUND: we recently showed that a hypothesized anti-aging and anti-inflammatory protein, namely Klotho, may contribute to the etiology and/or pathogenesis of multiple sclerosis (MS). In addition, Klotho function and its gene expression are dependent on inflammatory pathways. Accordingly, the aim of this study was to investigate the Klotho gene expression within peripheral blood mononuclear cells (PBMCs) of patients with MS. METHODS: Altogether, 30 patients with relapsing-remitting MS (RRMS) along with 30 age and sex-matched healthy individuals were enrolled in this study. Blood samples were obtained from all participants and then PBMCs were isolated. The quantitative Real-Time PCR was carried out for Klotho mRNA derived from PBMCs. RESULTS: The results showed that klotho gene expression in the PBMCs of patients with RRMS is nearly 2.5-fold less than healthy individuals (P=0.0006). CONCLUSION: This is the first study demonstrating a possible role of Klotho in the PBMCs of MS patients.

First report of isolation of Mycobacterium novocastrense from water supplies.

We herein present the first documented report associated with the isolation of Mycobacterium novocastrense from environment. The identification and characterization of four unrelated isolates, one from the surface water and the other three from hospital water, were achieved by various conventional and molecular tests including a genus-specific PCR for Mycobacterium based on 65-kDa heat shock protein (hsp) gene and 16S rDNA sequencing. Our findings might shed further light on the natural habitat of this rare Mycobacterium.