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The present study aimed to explore the involved lncRNA-miRNA-mRNA network in the cell cycle and proliferation after conventional treatments in Luminal A breast cancer patients.The candidate miRNAs (miRs), lncRNAs, and mRNAs were first taken from the Gene Expression Omnibus and TCGA databases. The lncRNA–miR–mRNA network was then constructed using the high-throughput sequencing data. The expression levels of selected targets were measured in the breast cancer and healthy samples by the Real-Time PCR technique and compared with the clinical outcomes by the Kaplan-Meier method.Our analysis revealed a group of differentially expressed 3 lncRNAs, 9 miRs, and 14 mRNAs in breast cancer patients. A significant expression decrease of the selected tumor suppressor lncRNAs, miRs, and genes and a substantial expression increase of the selected onco-lncRNAs, oncomiRs, and oncogenes were obtained in the patients compared to the healthy group. The plasma levels of the lncRNAs, miRs, and mRNAs were more significant after the operation, chemotherapy, and radiotherapy than the pre-treatment. The Kaplan-Meier analysis indicated that the patients with a high expression of miR-21, miR-20b, IGF1R, and E2F2 and a low expression of miR-125a, PDCD4, and PTEN had exhibited a shorter overall survival rate.Our results suggested that the underlying mechanisms of the lncRNA, miRs, and mRNAs and relevant signaling pathways may be considered predictive and therapeutic targets for breast cancer.

Several investigations have disclosed the involvement of the interleukin (IL)-23/IL-17 pathway in rheumatoid arthritis (RA) pathogenesis. Here we investigated the association of single nucleotide polymorphisms (SNPs) in the IL23 receptor (IL23R) gene with RA risk. In addition, the role of these SNPs with the inflammatory state of the patients were determined.In this case-control study, 200 RA cases and 200 healthy subjects were recruited. Using allelic discrimination real-time polymerase chain reaction, both IL23R rs10489629 and rs1004819 SNPs were genotyped. The messenger RNA (mRNA) expression levels of IL-23R, IL-23, and IL-17A were determined in peripheral blood mononuclear cells (PBMCs). The serum levels of IL-23 and IL-17A were also determined.The A allele (odds ratio [OR] = 1.52, 95% CI: 1.15-2.01; P = .0030), AA genotype (OR = 2.41, 95% CI: 1.33-4.35; P = .0035), and AG genotype (OR = 2.55, 95% CI: 1.56-4.16, P = .0002) of rs1004819 SNP was significantly associated with increased RA risk. The mRNA expression of IL-17A (fold change = 2.55, P = .00027), IL-23 (fold change = 1.62, P = .0081), and IL-23R (fold change = 1.59, P = .0077) was significantly upregulated in the PBMCs from RA patients compared to that of healthy controls. Serum levels of IL-17A (P = .00019) and IL-23 (P = .00055) was significantly higher in the RA patients compared to the controls. No significant association was detected between patient data and SNPs.The IL-23/IL-27 pathway plays a role in RA pathogenesis, but IL23R gene rs1004819 SNP might not be regulating this pathway in RA disease.

Interferon regulatory factor 5 (IRF5) has been described as an important factor in regulating inflammatory response and a key transcription factor in the immune system. In antiviral response, IRF5 promotes the expression of type 1 interferon (IFN) and is also important in the differentiation of macrophages towards pro-inflammatory phenotypes, regulating B-cell maturity and antibody production. Some cancer patients treated with IFNα manifest symptoms resembling systemic lupus erythematosus (SLE). An important mechanism in this response is IRF5 that triggers apoptosis. Herein, we discuss the functional importance of IRF5 in rheumatoid arthritis (RA) and SLE in a setting of polymorphic mutations at the human Irf5 locus. This paper describes murine models, the lessons of IRF functionality learned from these models and the consequences of autoimmune diseases. It is hypothesized that modulation of IRF5 activity may be beneficial in autoimmune diseases therapies.

We aimed to assess the association between opioid addiction and metabolic syndrome (MetS) risk and its components.We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN). The diagnosis of MetS was accomplished using three criteria of the International Diabetes Federation (IDF), Iranian IDF, and National Cholesterol Education Panel-Adult Treatment Panel III (NCEP-ATP III). Using a questionnaire, data for the demographic, anthropometric, and laboratory indices was collected.The prevalence of MetS was 38.30, 31.58, and 34.42% based on the IDF international, IDF Iranian, and NCEP-ATP III criteria. According to the IDF international criteria, 666 (17.45%) cases were using opioids and there was a statistically significant difference between opioid use and prevalence of MetS (p 0.001). Based on the NCEP-ATP III criteria, there was a significant difference in the prevalence of MetS based on opioid use (p 0.001). Use of opioids was associated significantly with a decreased odds of MetS in the multivariate model based on the IDF international (Adjusted OR = 0.85, 95% CI 0.74-0.98) and IDF Iranian criteria (Adjusted OR = 0.83, 95% CI 0.72-0.95).Prevalence of MetS was lower in subjects using opioids. Opioid use was associated with a decreased risk of MetS development.

Introduction: Cervical cancer is recognized as one of the major causes of mortality among elderly women. Although there are several different therapeutic worldwide guidelines, many researchers have focused on screening new methodologies and technologies to elevate the efficiency of cervical cancer treatment. The simultaneous use of photodynamic therapy (PDT) along with chemotherapy as cisplatin has achieved good aims in the treatment of cervical cancer. Methods: A2780 cells were treated with cisplatin, photodynamic progress (laser with methylene blue as a photosensitizer compound) and a combination of cisplatin and PDT. The lithic effect of the laser, methylene blue and their combination and the IC50 value of cisplatin were calculated for each group. The amount of malondialdehyde (MDA) as membrane lipid peroxidation product and released lactate dehydrogenase was measured in the medium. The toxicity of each agent was evaluated by the MTT technique. Results: The results show that a combination of PDT and chemotherapeutic agent cisplatin caused a twofold decrease in viable cervical cancer cells compared to each therapeutic progress. The combination of both laser therapy and cisplatin enhanced cancer cell membrane disruption by increased membrane lipid peroxidation and apoptotic enzyme activation by the elevation of lactate dehydrogenase activity. Conclusion: The results indicated that cisplatin combined with PDT had a greater therapeutic effect on A2780 as a cervical cancer cell line. Therefore, PDT in combination with chemotherapy enhances the effectiveness of chemotherapeutic agents by the disruption of the cancer cell membrane and switching the apoptosis progress with less adverse effects.

Background Recent studies report incongruent finds regarding the addition of pegylated interferon -alpha (Peg- IFNα) to nucleos(t)ide analogues. This study was designed to compare the efficacy of Peg- IFNα and tenofovir disoproxil fumarate (TDF) combination therapy with each of the treatments separately. Methods In this open-label, randomized clinical trial, treatment-naive hepatitis B e antigen (HBeAg)-negative patients were randomly assigned to three treatment groups: Group A: Peg- IFNα (180 mcg/week) with TDF (300 mg/day); Group B: TDF (300 mg/day); and Group C: Peg- IFNα (180 mcg/week). The intervention spanned 48 weeks and patients were followed up every 12 weeks. The primary end-point was HBV DNA load Results Groups A, B and C each comprised of 22, 23 and 22 patients, respectively. The number of patients with HBV DNA suppression in group A was significantly higher compared to groups B and C (P = 0.034). No significant difference was observed in the normalization trends of serum ALT levels between the three groups (P = 0.082). At week 48, combination therapy was significantly more effective in suppressing HBV DNA concentration to below the level of detection than TDF monotherapy (OR = 2.1, 95%CI: 1.18–4.15; P = 0.034). Furthermore, a comparison between monotherapy arms revealed that both interventions had similar effects on the overall outcome (OR = 1.24, 95%CI: 1.02–5.8; P = 0.062). Conclusion A Peg- IFNα and TDF combination therapy resulted in improved virologic response and was safe in HBeAg negative patients. Monotherapy with Peg-IFNα or TDF procured limited benefits in comparison. Trial registration This study was registered in the Iranian Registry of Clinical Trials (IRCT20181113041635N1).

The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case–control studies (RR = 0.47; 95% CI, 0.39-0.55; I2 = 85.1%; P

Vitamin D level varies according to the geographic location. This study was conducted to evaluate Vitamin D level in the serumsamples of Systemic lupus erythematosus (SLE) patients from the Iranian population and determine its association with SLE diseaseactivity index (SLEDAI), sun exposure, smoking, photosensitivity, sun protector cream use, and drug regimen. In this crosssectional study, 200 patients were included. The patient’s data were obtained using a questionnaire. The enzyme-linkedimmunosorbent assay (ELISA) technique was used to determine Vitamin D level in the serum samples of the patients. The studypopulation was comprised of 27 (13.5%) males and 173 (86.5%) females, with a mean age of 38.46 ± 13.24 years. The serumlevel of Vitamin D was 13.62 ± 3.22 ng/ml in the patients. Vitamin D deficiency was observed in 104 (52%) patients. There wasa statistically positive correlation between vitamin D level and duration of sun exposure (CC = 0.57, P = 0.004). A statisticallysignificant negative correlation was seen between vitamin D level and SLEDAI (CC = -0.41, P = 0.013).Vitamin D level was significantly (P = 0.030) lower in the SLE patients with photosensitivity. SLE patients using sunprotector cream had significantly (P = 0.002) lower level of Vitamin D. Patients receiving glucocorticoid drugs hadsignificantly (P = 0.001) lower levels of Vitamin D in comparison to the patients not receiving glucocorticoids. Vitamin D isinvolved in the disease activity of SLE patients. It is important to include vitamin D supplementation in the drug regimen of SLEpatients, especially when it includes glucocorticoids.

Excessive inflammation has been implicated in the immunopathogenesis of coronavirus disease 2019 (COVID-19). In the current study, the involvement of S100 calcium binding protein S100A4, S100A9, and S100A10 in the inflammatory settings of COVID-19 patients were evaluated.Peripheral blood samples were obtained from 65 COVID-19 subjects and 50 healthy controls. From the blood samples, RNA was extracted and cDNA was synthesized, and then the mRNA expression levels of S100A4, S100A9, and S100A10 were measured by Real-time PCR.The mRNA expression of S100A4 (fold change [FC] = 1.45, P = 0.0011), S100A9 (FC = 1.47, P = 0.0013), and S100A10 (FC = 1.35, P = 0.0053) was significantly upregulated in COVID-19 patients than controls. The mRNA expression of S100A4 (FC = 1.43, P = 0.0071), (FC = 1.66, P = 0.0001), and S100A10 (FC = 1.63, P = 0.0003) was significantly upregulated in the severe COVID-19 subjects than mild-to-moderate subjects. There was a significant positive correlation between mRNA expression of S100A4 (ρ = 0.49, P = 0.030), S100A9 (ρ = 0.55, P = 0.009), and S100A10 (ρ = 0.39, P = 0.040) and D-dimer in the COVID-19 patients. The AUC for S100A4, S100A9, and S100A10 mRNAs were 0.79 (95% CI 0.66-0.92, P = 0.004), 0.80 (95% CI 0.67-0.93, P = 0.002), and 0.71 (95% CI 0.56-0.85, P = 0.010), respectively.S100A4, S100A9, and S100A10 play a role in the inflammatory conditions in COVID-19 patients and have potential in prognosis of severe form of COVID-19. Targeting these modules, hopefully, might confer a therapeutic tool in preventing sever symptoms in the COVID-19 patients.

In the last decade, transcriptome analyses have discovered thousands of long non-coding RNAs (lncRNAs) which are assumed as a fundamental part of the gene regulatory networks in the cell. Intriguingly, lncRNAs are abundantly enriched in the brain, displaying elaborate spatiotemporal expression profiles and modulation. They diversely participate in the delicate regulation of the central nervous system (CNS) development including self-renewal maintenance, cell fate decision, synapse plasticity, synaptogenesis and memory formation. Moreover, lncRNAs have vastly demonstrated correlations with mental illnesses such as neuropsychiatric disorders (NPDs), implying the vital jobs of these yet poorly-understood transcripts. Here, we underlie the accumulating evidence for the significance of lncRNAs in neural networks and their impairment in several NPDs including autism spectrum disorder (ASD), schizophrenia (SZ), intellectual disability (ID), major depressive disorder (MDD), Rett syndrome (RTT) and others.

The response of biological systems to various types of radiations have many ambiguous dimensions. Among ionizing radiations, in vitro external gamma radiation therapy has mostly studied as model to declare the biological system challenges with radiation effects. Cell/organism exposure to gamma radiation, caused cascade of ionization events such as severe irreversible biological damages. However, the biological responses and oxidative stress related mechanisms under acute radiation conditions poorly understood in inflammatory systems. Following study tried to give a model about ionizing radiation effect on the macrophage that had a key role in inflammation mechanisms; to evaluate the impact of radiotherapy approach for inflammatory disease as rheumatoid arthritis. To this aim, Macrophage cell line (RAW 264.7) culture, exposed to different doses of gamma radiation (0,4, 6, 8, 10 Gy). Cell viability, apoptosis, cell cycle, migration; NO and PGE2 production; expression of pro-inflammatory and apoptotic genes and cytokine secretion of macrophages was also evaluated.The results showed that gamma treatment, at 4 Gy radiation, have slight effect on macrophage characteristics and cytokine secretion pattern. Versus, higher doses (8 and 10 Gy) increased DNA damage, expression of apoptotic genes and secretion of NO and PGE2 cytokines. 6 Gy radiation, the maximum radiation dose, show moderate nondestructive effects and inflammation process modulation. In this study, doses higher than 6 Gy of Gamma radiation caused cell mortality. It seems that 6 Gy Gamma radiation modulate the inflammatory cascade caused by macrophage cell, as a central core of autoimmune inflammatory disease in acute dose radiation therapy.

Background and Objective Patients with panic disorder (PD) suffer from elevated oxidative stress as a consequence of serotonin metabolism disorder. These patients have elevated serotonin concentration and catabolism of serotonin via monoamine oxidase. The aim of the present study was to evaluate serum homocysteine concentration and its relationship with oxidative stress level in PD patients, regarding homocysteine as a diagnostic biomarker of heart disease. Materials & Method Sixty patients with PD according to the DSM‐5 diagnostic criteria for a panic attack and 60 healthy individuals were included in the present study. Peripheral venous blood samples were taken from patients. Erythrocytes and serum were separated from blood, and RBC hemolysates were prepared to investigate oxidative stress indices including glutathione and glutathione peroxidase. Serum homocysteine and carbonyl groups concentrations were measured in all samples. Data were analyzed using ANOVA, and p, The aim of the present study was to evaluate serum homocysteine concentration and its relationship with oxidative stress levels in patients with PD, regarding homocysteine as a diagnostic biomarker of heart disease. Our findings support that, patients with PD experience higher levels of oxidative stress, due to impaired serotonin metabolism, which is related to the prognosis of heart disease in these patients.

Background: Previous studies have shown that several microRNAs (miRNAs) are dysregulated in the whole blood as well as diverse cells and tissues from rheumatoid arthritis (RA) patients. The aim of the current study was to determine if the expression of miR-146a, miR-103a, and miR-155 in whole blood of RA patients could confer potential markers in evaluating of activity-severity of the disease in RA patients with established disease. Methods: Whole blood samples were obtained from 30 RA patients and 30 healthy subjects. The RNA content of blood samples was isolated, cDNA was synthesized, and transcript levels of miR-146a, miR-103a, and miR-155 were determined using Real-time PCR. The clinicopathological characteristics of the patients were also evaluated. Results: It was detected that expression level of miR-146a (fold change=1.85, P=0.004), miR-103a (fold change=2.44, P=0.0018), and miR-155 (fold change=1.94, P=0.0025) were significantly upregulated in the whole blood samples of RA patients in comparison to that of healthy subjects. Expression level of miRNAs was correlated with clinicopathological characteristics of the patients, including Disease Activity Score 28 (DAS28), Simple Disease Activity Index (SDAI), 28Tender Joint Count (TJC-28), 28Swollen Joint Count (SJC-28), C-reactive protein (CRP), Rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Conclusions: Upregulated levels of miR-146a, miR-103a, and miR-155 in the whole blood samples of RA patients could confer a potential marker of activity-severity of the disease in RA patients with established disease.

Background/objective: This study aimed to investigate the impacts of a 12-week training of the aerobic exercise (AE), resistance exercise (RE), and combined exercise (CE) on the serum levels of nesfatin-1, irisin-1 and some other metabolic and anthropometric indices in overweight women with metabolic syndrome. Methods: Sixty overweight women with metabolic syndrome were assigned equally into four groups: aerobic exercise (AE, n = 15), resistance exercise (RE, n = 15), combined exercise (CE, n = 15), and control (n = 15). All groups underwent 12 weeks of intervention. The study variables were measured before and 24 h after the intervention period. Results: Twelve weeks of training resulted in an increase of irisin-1 in the AE and CE groups and nesfatin-1 in all the intervention groups. As expected, all the trained groups exhibited a positive alteration in anthropometric indices and lipid profile in comparison with the control group. Besides, compared with the control group, insulin resistance (based on the homeostatic model assessment) in AE (p = 0.022), RE (p = 0.032), and CE (p < 0.001) groups were reduced significantly. According to the observed changes in the measured indices, serum irisin-1 was significantly correlated with body weight, BMI, body fat percentage, fasting insulin, and HOMA-IR. However, with regard to nesfatin-1, only a negative correlation was observed with body fat percentage and LDL-cholesterol. Conclusions: The 12-week systematic training program changed circulating irisin-1 and nesfatin-1. Also, change in the serum irisin-1 and nesfatin-1 were correlated with the change in glycemic and anthropometric indices in addition to LDL-cholesterol. Also, exercise training significantly reduced fasting insulin and HOMA-IR in all the intervention groups. RCT Registration Code: IRCT20180806040721N2.

Risk factors for clinical outcomes of COVID-19 pneumonia have not yet been well established in patients with underlying liver diseases. Our study aimed to describe the clinical characteristics and outcomes of COVID-19 infection among patients with underlying liver diseases and determine the risk factors for severe COVID-19 among them. In a retrospective analytical study, 1002 patients with confirmed COVID-19 pneumonia were divided into two groups: patients with and without underlying liver diseases. The admission period was from 5 March to 14 May 2020. The prevalence of underlying conditions, Demographic data, clinical parameters, laboratory data, and participants' outcomes were evaluated. Logistic regression was used to estimate the predictive factors. Eighty-one (8%) of patients had underlying liver diseases. The frequencies of gastrointestinal symptoms such as diarrhea and vomiting were significantly higher among patients with liver diseases (48% vs. 25% and 46.1% vs. 30% respectively, both P Adj) 1.81, 95% CI 1.21–3.11, P = 0.011] and blood group A (ORAdj 1.59, 95% CI 1.15–2.11, P = 0.001) were associated with progression of symptoms of COVID-19. The presence of underlying liver diseases should be considered one of the poor prognostic factors for worse outcomes in patients with COVID-19.

BACKGROUND Several genome-wide association studies have revealed a genetic background with respect to susceptibility to rheumatoid arthritis (RA). Although several individual case-control studies have evaluated the role of protein tyrosine phosphatase non-receptor 22 (PTPN22) gene rs2476601 single nucleotide polymorphism (SNP) in conferring a risk for RA, the results have been conflicting. Hence, this meta-analysis was aimed to provide a solution for this issue. METHODS To search for studies assessing the association between the PTPN22 gene rs2476601 SNP and the risk of RA, a systematic search was conducted in the main databases, including PubMed, Scopus and Web of Science, prior to December 2019. The odds ratio (OR) and corresponding 95% confidence interval (CI) was calculated to assess the possibility of association risk. RESULTS The literature search identified 52 case-control studies. The pooled analysis detected significant positive association of rs2476601 in all genetic models, including dominant model (OR = 1.69, 95% CI = 1.55-1.84, P < 0.001), recessive model (OR = 2.50, 95% CI = 2.06-3.05, P < 0.001), allelic model (OR = 1.80, 95% CI = 1.60-2.2, P < 0.001), TT versus CC model (OR = 2.79, 95% CI = 2.28-3.41, P < 0.001) and CT versus CC model (OR = 1.59, 95% CI = 1.50-1.67, P < 0.001). Analyses based on population stratification indicated that rs2476601 SNP strongly increased the risk of RA in Caucasians and Africans under all genotype models. CONCLUSIONS This meta-analysis reports that the PTPN22 gene rs2476601 SNP increases RA risk, especially in Caucasians and Africans.

Background Attention-deficit/hyperactivity disorder (ADHD), a common psychiatric disorder, is identified by abnormal levels of impulsivity, inattention, and hyperactivity. MiRNAs play important roles in neural network development of the brain. Circulating miRNAs (cmiRNAs) are offered as promising noninvasive markers for psychiatric disorders. In this study, the expression level of neurologically relevant miRNAs was evaluated in serum samples of ADHD individuals. Methods RNA extraction was performed for 60 subjects with ADHD and 60 healthy controls, and the cDNAs were synthesized for all the miRNAs. The expression level of 84 cmiRNAs was then examined in 4 ADHD subjects and 4 controls. The altered expression of 10 cmiRNAs was further evaluated in validation cohort comprising 56 ADHD and 56 control samples by qPCR. The diagnostic power of the miRNAs was determined by use of Receiver-operating characteristic (ROC) analysis. The cmiRNAs target genes were predicted using DIANA mirPath software and gene ontology enrichment analysis was performed using Cytoscape CLUGO. Results Initially, 10 miRNAs showed differential expression in ADHD individuals. Further analysis confirmed four miRNAs (hsa-miR-101-3p, hsa-miR-130a-3p, hsa-miR-138-5p and hsa-miR-195-5p) upregulated and one miRNA (hsa-miR-106b-5p) downregulated. These miRNAs showed significant predictive values for discriminating ADHD individuals. Enrichment analysis highlighted the involvement of the deregulated cmiRNAs in many canonical neurobiological pathways and mechanisms. Conclusions Our report is the first comprehensive study on the expression profiling of miRNAs in serum of ADHD subjects. These findings suggest a set of cmiRNAs as potential noninvasive biomarkers for ADHD.

Many attempts are being made to find an association between varicocele characteristics and sperm parameters. In this study, we investigated the association between a newly introduced varicocele reflux grading pattern and sperm parameters, as well as its effect on spermogram improvement after varicocelectomy. In a prospective study, 73 patients with a clinical single-sided varicocele who underwent corrective varicocelectomy were included. Reflux pattern was determined on Color Doppler Ultrasound (CDUS) and categorized into four grades: grade 1 (retrograde), grade 2 (augmentation), grade 3 (enhancement), and grade 4 (stasis). The association of pre- and postoperative spermogram with the patients’ reflux pattern was evaluated. A significant positive association was found between the venous diameter and reflux pattern. Higher grades of the reflux pattern were associated with the more severe hemodynamic pattern of the reflux (shunt type). A significant association was found between the reflux pattern and preoperative semen characteristics, and this association was more prominent in constant venous diameter. In this respect, the enhancing reflux type was associated with the most impaired preoperative sperm count, motility, and morphology. The enhancing type also revealed the most improvement in spermogram after varicocelectomy. Patients with a higher reflex grade, particularly enhancing pattern, will most benefit from the surgical correction of varicocele. These findings suggest reflux pattern as a promising prognostic factor for a favorable outcome after varicocelectomy.

Vitamin D is involved in immune system modulation as well as in calcium and bone homeostasis, hence plays a role in rheumatoid arthritis (RA) etiopathogenesis. A bulk of studies in different populations have assessed the association between the vitamin D receptor (VDR) gene polymorphisms and the risk of RA, reporting conflicting results. Therefore, we designed a meta-analysis to comprehensively evaluate the association of VDR gene polymorphisms and RA risk. All potential studies reporting the association between VDR gene polymorphisms and susceptibility to RA published till February 2020 were retrieved through systematic search of database, including Scopus and MEDLINE. Strength of pooled association was determined through calculating the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analysis was performed by stratifying the studies by population type. This meta-analysis included 23 eligible studies (21 articles) overall. We noticed that FokI SNP had a significant protective association with susceptibility to RA in the overall analysis as well as in Europeans and Asians. TaqI SNP decreased the RA risk in Africans and Arabs, but not in the overall analysis. Likewise, BsmI SNP and RA risk in the overall population analysis was not significant. Interestingly, BsmI polymorphism increased RA risk in Africans. This meta-analysis offers a significant association between VDR gene polymorphism and susceptibility to RA in both overall and ethnic-specific analysis. However, different polymorphisms acted inversely in increasing or decreasing RA risk in different populations.

Background The level of angiotensin-converting enzyme 2 (ACE2) expression in different tissues is essential in the sensitivity, symptoms and consequences of COVID-19 infection. It seems that zinc is involved in the structure of the ACE2 enzyme has been identified; nonetheless, the relationship between ACE2 expression and zinc serum levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is still unclear. This study aimed to evaluate the expression of ACE2 in peripheral blood-derived immune cells of COVID-19 patients and its relationship with serum zinc levels. Methods Thirty healthy subjects and thirty patients with COVID-19 were enrolled in this study. The COVID-19 infection was confirmed by positive real-time polymerase chain reaction (RT-PCR) and radiological data. Peripheral blood samples were taken from healthy subjects and COVID-19 patients. Whole blood samples were also used to measure ACE2 gene expression by RT-PCR technique. The correlation matrix evaluated the relationship between ACE2 expression, serum zinc levels, and other related variables. Results The outcomes showed no considerable alteration in serum zinc levels between patients and the control group. Likewise, the ACE2 gene expression results showed a significant decrease in this receptor's expression in COVID-19 patients compared with the healthy subjects. A significant positive correlation was observed between serum zinc level and ACE2 gene expression in patients with COVID-19. Conclusion The immune system seems to reduce the mRNA expression of the ACE2 in the peripheral blood leukocytes following SARS-CoV-2 infection. Moreover, zinc deficiency can make patients more susceptible to SARS-CoV-2 infection.

Introduction This study examined the process of deriving mature oligodendrocytes from human dental pulp stem cells (hDPSCs) via addition of cerebrospinal fluid (CSF). Methods The hDPSCs were cultured in the presence of retinoic acid and CSF. The oligodendrocytes were confirmed using immunocytochemistry for specific glial markers, namely Olig2 and MBP markers. Results The differentiated oligodendrocytes were immunopositive for Olig2 and MBP markers at the end of induction phase. Conclusion It is concluded that this study indicated the glial differentiation of hDPSCs in the presence of CSF and appropriate inducers, which is a usable therapeutic technique in neuroregenerative medicine (Fig. 3, Ref. 24).

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, in which an epigenetic implication in the disease etiopathogenesis has been noted. Here in this meta-analysis, we attempted to investigate the pooled association of methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and susceptibility to RA risk. A systematic search was performed in the main databases, including MEDLINE and Scopus to search for studies assessing the association between MTHFR gene C677T and A1298C polymorphisms and the risk of RA prior to December 2019. In this meta-analysis, 15 studies with 2165 patients and 1751 healthy controls for C677T SNP and 14 studies containing 2021 patients and 1760 healthy controls for A1298C SNP were included. A significant positive association between C677T SNP and RA risk was recognized in the dominant, recessive, and allelic model, but not TT and CT genotypes. The results indicated that the risk of RA in African population was increased under all genotype models while these results were repeated in Asian population just for recessive model, allelic model, and TT genotype. Moreover, the analysis of A1298C SNP demonstrated a significant association in overall population according to only the recessive model and CC genotype. Subgroup analysis according to the genotyping method indicated that RFLP-PCR method could impress the results of association between MTHFR gene A1298C and C677T SNPs and RA risk. The outcome of this meta-analysis indicated that MTHFR gene C677T SNP was much possibly be associated with RA risk.

One of the promising approaches for the treatment of cardiac disease is stem cell therapy. In this study, we compared the cardiomyogenic differentiation rate, from human adipose-derived stem cells (hADSCs) in a three-dimensional (3D) hanging drop (HD) spheroid culture system, versus a two-dimensional (2D) culture condition at different concentrations of 5-azacytidine (5-Aza). 5-Azaytidine (5-Aza) is a pyrimidine nucleoside analogue of cytidine that initiates cell differentiation programs through DNA demethylation. The hADSCs were isolated and cultured both in 2D and 3D HD conditions, with either 10 or 50 μM concentrations of 5-Aza. Then DNA content, gene expression, and protein content were analyzed. 3D HD culture resulted in a higher percentage of cells in G0/G1 and S phase in the cell division cycle, whereas 2D culture led to a greater percentage of cells in the G2/M phase. A significantly higher gene expression rate of HAND1, HAND2, cTnI, Cx43, βMHC, GATA4, NKX2.5, and MLC2V was observed in HD treated with 50 μM 5-Aza. This was confirmed by immunocytochemistry. These findings suggest that 50 μM concentration of 5-Aza can induce hADSCs to differentiate into cardiomyocytes. The differentiation rate was significantly higher when accompanied by the 3D HD culture system. This work provides a new culture system for cell differentiation for cardiovascular tissue engineering.

BACKGROUND: The adult human heart muscle cells, cardiomyocytes are not capable of regenerate after injury. Stem cells are a powerful means for future regenerative medicine because of their capacity for self-renewal and multipotency. Several studies have reported the cardiogenic potential in human adipose tissue-derived stem cells (ADSCs) differentiation, but there is still no efficient protocol for the induction of cardiac differentiation by 5-azacytidine (5-Aza). The present study involves characterization and mainly, the ultrastructure of ADSCs derived cardiomyocyte-like cells. METHODS: The cultured ADSCs were treated with 50 µM 5-Aza for 24 hours, followed by a 10-week extension. At different time points, cardiomyocyte-like cells were assessed by qRT-PCR and were evaluated by transmission electron microscopy at 10(th) week. RESULTS: The expression of cardiac-specific markers entailing cardiac troponin I (cTnI), connexin 43, myosin light chain-2v (Mlc-2v), increased over 10 weeks and the highest expression was at 10(th) week. The expression of the β-myosin heavy chain (β-MHC) increased significantly over 5 weeks and then decreased. At the ultrastructural level myofibrils, transverse tubules (T-tubules), sarcoplasmic reticular membrane, and intercalated discs were present. CONCLUSIONS: These data suggest that treatment with 5-Aza in high dose could promote differentiation of ADSCs into cardiomyocyte-like cells. These differentiated cells could be used for regeneration of damaged cardiomyocytes with the 3D scaffold for delivery of the cells.

Osteoarthiritis (OA) is the most prevalent disease of articulating joints in human that frequently results in joint pain, movement limitations, inflammation, and progressive degradation of articular cartilage. The etiology of OA is not completely clear and there is no full treatment for this disease. Molecular investigations have revealed the involvement of non-coding RNAs such as Long non-coding RNAs (lncRNAs) in OA pathogenesis. LncRNAs play roles in multiple cellular and biological processes. Moreover, numerous lncRNAs are differentially expressed in human OA cartilage. In this review, we underlie the increasing evidence for the critical role of lncRNAs in OA pathogenesis reviewing the latest researches.

Differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes is a complex phenomenon, and attempts to find an effective inducing agent are still ongoing. We studied the effect of fibrin scaffold and sodium valproate (VPA, as a histone deacetylase inhibitor) on the differentiation of human adipose-derived stem cells (hADSCs) into cardiomyocyte-like cells. The cells were cultured in culture flask (2D) and in fibrin scaffold (3D), fabricated of human plasma fibrinogen, with and without VPA (1 mM). QRT-PCR, Western blot, and immunochemistry assays were used to evaluate the expression of cardiac markers at gene and protein levels. High levels of CD44, CD90, CD73, and CD105 were expressed on the surface of hADSCs. Treated encapsulated hADSCs (3D) presented significantly higher mRNA expression of HAND1 (1.54-fold), HAND2 (1.59-fold), cTnI (1.76-fold), MLC2v (1.4-fold), Cx43 (1.38-fold), βMHC (1.34-fold), GATA4 (1.48-fold), and NKX2.5 (1.66-fold) in comparison to 2D conditions at four weeks after induction. The protein expressions of NKX2.5 (0.78 vs 0.65), cTnI (1.04 vs 0.81), and Cx43 (1.11 vs 1.08) were observed in the differentiated cells both in 3D and 2D groups, while control cells were absolutely negative for these proteins. The frequency of cTnI and Cx43-positive cells was significantly higher in 3D (24.2 ± 15 and 12 ± 3%) than 2D conditions (19.8 ± 3 and 10 ± 2%). Overall, the results showed that VPA can increase cardiomyogenesis in hADSCs and that fibrin scaffold enhances the inductive effect of VPA. Results of this study may improve cell-based protocols for implementation of more successful cardiac repair strategies.