Association of vitamin D receptor genetic polymorphisms with the risk of infertility: a systematic review and meta-analysis.

BACKGROUND: The causes of infertility have remained an important challenge. The relationship between VDR gene polymorphisms and infertility has been reported, with controversial findings. OBJECTIVE AND RATIONALE: We aimed to determine this relationship by conducting a systematic review and meta-analysis. SEARCH METHODS: The study was started with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration and the final draft was registered as a protocol in PROSPERO (ID: CRD42023416535). The international electronic databases including PubMed (Medline), Scopus, Web of Sciences, and Cumulative Index to Nursing and Allied Health Literature (CINHAL) were searched until January 30, 2023, by using appropriate keywords. The quality of the final studies was assessed using the NOS Checklist for case-control studies. The odds ratios (ORs) for each of the genetic models were pooled, and a subgroup analysis based on geographical region and types of infertility was carried out by the MetaGenyo online tool. OUTCOMES: Case-control studies including 18 and 2 studies about infertility in women and men, respectively, and 4 miscarriage studies were entered into the meta-analysis. The VDR gene TaqI polymorphism was associated with infertility susceptibility in women in the allele contrast [OR = 1.2065, 95% CI (1.0846-1.3421); P = 0.0005], Recessive model [OR = 1.3836, 95% CI (1.1197-1.7096); P = 0.002], Dominant model [OR = 1.2146, 95% CI (0.0484-1.4072); P = 0.009], Homozygote [OR = 1.4596, 95% CI (1.1627-1.8325); P = 0.001], and TT vs. Tt [OR = 1.2853, 95% CI (1.0249-1.6117); P = 0.029. ApaI and FokI gene polymorphisms were found to be significantly protective SNPs against women and men infertility in the Dominant model [OR = 0.8379, 95% CI (0.7039- 0.9975); P = 0.046] and Recessive model [OR = 0.421, 95% CI (0.1821-0.9767); P = 0.043], respectively. Sub-group meta-analysis showed a protection association of ApaI in dominant [OR = 0.7738, 95% CI = 0.6249-0.9580; P = 0.018] and AA vs. aa [OR = 0.7404, 95 CI% (0.5860-0.9353) P = 0.011725] models in PCOS subgroup, however, a negative association with idiopathic infertility was found in AA vs. Aa [OR = 1.7063, 95% CI (1.1039-2.6375); P = 0.016187] and Aa vs. aa [OR = 0.6069, 95% CI (0.3761-0.9792); P = 0.040754]. TaqI SNP was significantly associated with infertility in the African population and BsmI was associated with the disease mostly in the Asian population. CONCLUSION: This meta-analysis showed that the TaqI polymorphism may be linked to women's infertility susceptibility. However, ApaI and FokI might be the protective SNPs against infertility in Women and men, respectively.

Evaluation of Genetic Content of the CRISPR Locus in Listeria monocytogenes Isolated From Clinical, Food, Seafood and Animal Samples in Iran.

CRISPR arrays, which are organized to fight against non-self DNA elements, have shown sequence diversity that could be useful in evolution and typing studies. In this study, 55 samples of L. monocytogenes isolated from different sources were evaluated for CRISPR sequence polymorphism. The CRISPR loci were identified using CRISPR databases. A single PCR assay was designed to amplify the target CRISPRs using an appropriate universal primer. Sequencing results were analyzed using CRISPR databases and BLASTn, and the CRISPR locus was present in all the strains. Three hundred repeats including 55 terminal repeats were identified. Four types of consensuses direct repeat (DR) with different lengths and sequences were characterized. Sixty repeat variants were observed which possessed different polymorphisms. Two hundred and fifty spacers were identified from which 35 consensus sequences were determined, indicating the high polymorphism of the CRISPR spacers. The identified spacers showed similarities to listeria phage sequences, other bacterial phage sequences, plasmid sequences and bacterial sequences. In order to control the bacterial outbreaks, a robust and precise system of subtyping is required. High levels of polymorphism in the CRISPR loci in this study might be related to the origin and time of the samples' isolation. However, it is essential to assess, on a case-by-case basis, the characteristics of any given CRISPR locus before its use as an epidemiological marker. In conclusion, the results of this study showed that the use of sequence content of CRISPR area could provide new and valuable information on the evolution and typing of the L. monocytogenes bacterium.

Recent findings on the role of microRNAs in genetic kidney diseases.

BACKGROUND: MicroRNAs (miRNAs) are non-coding, endogenous, single-stranded, small (21-25 nucleotides) RNAs. Various target genes at the post-transcriptional stage are modulated by miRNAs that are involved in the regulation of a variety of biological processes such as embryonic development, differentiation, proliferation, apoptosis, inflammation, and metabolic homeostasis. Abnormal miRNA expression is strongly associated with the pathogenesis of multiple common human diseases including cardiovascular diseases, cancer, hepatitis, and metabolic diseases. METHODS AND RESULTS: Various signaling pathways including transforming growth factor-ß, apoptosis, and Wnt signaling pathways have also been characterized to play an essential role in kidney diseases. Most importantly, miRNA-targeted pharmaceutical manipulation has represented a promising new therapeutic approach against kidney diseases. Furthermore, miRNAs such as miR-30e-5p, miR-98-5p, miR-30d-5p, miR-30a-5p, miR-194-5p, and miR-192-5p may be potentially employed as biomarkers for various human kidney diseases. CONCLUSIONS: A significant correlation has also been found between some miRNAs and the clinical markers of renal function like baseline estimated glomerular filtration rate (eGFR). Classification of miRNAs in different genetic renal disorders may promote discoveries in developing innovative therapeutic interventions and treatment tools. Herein, the recent advances in miRNAs associated with renal pathogenesis, emphasizing genetic kidney diseases and development, have been summarized.

A Proposed TUSC7/miR-211/Nurr1 ceRNET Might Potentially be Disturbed by a cer-SNP rs2615499 in Breast Cancer.

Evidence and in silico analyses showed that TUSC7, miR-211, and Nurr1 may be involved in BC pathogenesis by ceRNET signaling axis. This study aimed to investigate the potential role of TUSC7/miR-211/Nurr1 ceRNET and rs2615499 variant as a novel cer-SNP in BC subjects. The expression assays were conducted by qPCR on tumor tissues (n = 50), tumor-adjacent normal tissues (TANTs) (n = 50), and clinically healthy control tissues (n = 50). The expression of TUSC7 and Nurr1 significantly decreased, but the level of miR-211 significantly increased in tumor tissues compared to TANTs and healthy normal tissues. Altered expression of TUSC7 and miR-211 was associated with poor prognosis of patients. The Nurr1 exhibited a double-edged sword-like activity in BC. In addition, TUSC7, Nurr1, and miR-211 expressions were significantly related to a novel BC-associated rs2615499 (A > C) located in the miR-211 binding site on Nurr1 3'-UTR. In the second part of the study, a case-control study was performed on BC patients (n = 100) and matched healthy controls (n = 100). The genomic DNA was isolated and genotyping was performed using Tetra-Primer ARMS PCR. The CC and AC genotypes were associated with higher expression levels of Nurr1 and worse outcomes of the disease. Our findings revealed that TUSC7 functions as a tumor suppressor in BC potentially via miR-211/Nurr1, which might be disturbed by the cer-SNP rs2615499. However, functional studies are needed to validate these results.

Toxicological profile of lipid-based nanostructures: are they considered as completely safe nanocarriers?

Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following interactions with organelles and macromolecules can result in negative effects on cells, especially, they can induce cytotoxicity, epigenicity, genotoxicity, and cell death. Lipid-based nanomaterials (LNPs) are one of the most important achievements in drug delivery mainly due to their superior physicochemical and biological characteristics, particularly its safety. Although they are considered as the completely safe nanocarriers in biomedicine, the lipid composition, the surfactant, emulsifier, and stabilizer used in the LNP preparation, and surface electrical charge are important factors that might influence the toxicity of LNPs. According to the author's opinion, their toxicity profile should be evaluated case-by-case regarding the intended applications. Since there is a lack of all-inclusive review on the various aspects of LNPs with an emphasis on toxicological profiles including cyto-genotoxiciy, this comprehensive and critical review is outlined.

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis.

The interplay between H2 S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H 2 S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L-NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L-NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H 2 S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.

A simple and low cost tetra-primer ARMS-PCR method for detection triazole-resistant Aspergillus fumigatus.

The mutation at codon L98 accompanied by a tandem repeat of 34 base pairs (TR34/L98H) in the 5´upstream region of cyp51A is the principal mechanism of triazole resistance of Aspergillus fumigatus. We aimed to evaluate a simple and low-cost tetra-primer amplification refractory mutation system (ARMS)-PCR technique for detection of TR34/L98H mutations in the cyp51A gene of azole-resistant A. fumigatus. The tetra-primer ARMS-PCR assay optimized by four primers in one reaction consists of external primers for detection of tandem repeats in the promoter region and internal primers for detection of a point mutation in codon 98 (L98H) in the cyp51A gene of azole-resistant A. fumigatus. The specificity of TR34/L98H mutation detection was assessed by testing 36 clinical and environmental A. fumigatus strains. The tetra-primer ARMS-PCR assay from A. fumigatus, containing wild-type sequence (T allele) and L98H mutation at cyp51A (A allele), yielded two DNA fragments of 908 bp and 740 bp and two of 942 bp and 212 bp, respectively. None of the A. fumigatus isolates without the TR34/L98H mutation yielded false-positive results. The ARMS-PCR assay was 100% concordant with DNA sequencing results. Prevalence and screening of the TR34/L98H mutation in the cyp51A gene in A. fumigatus isolates may now be determined by a fast, low-cost, and simple method in resource-poor settings.

Association of SHMT1, MAZ, ERG, and L3MBTL3 Gene Polymorphisms with Susceptibility to Multiple Sclerosis.

Multiple sclerosis (MS) is the most common inflammatory and chronic disease of the central nervous system (CNS). A complex interaction between genetic, environmental, and epigenetic factors is involved in the pathogenesis of MS. With the advancement of GWAS, various variants associated with MS have been identified. This study aimed to evaluate the association of single-nucleotide polymorphisms (SNPs) rs4925166 and rs1979277 in the SHMT1, MAZ rs34286592, ERG rs2836425, and L3MBTL3 rs4364506 with MS. In this case-control study, the association of five SNPs in SHMT1, MAZ, ERG, and L3MBTL3 genes with relapsing-remitting MS (RR-MS) was investigated in 190 patients and 200 healthy individuals. Four SNPs including SHMT1 rs4925166, SHMT1 rs1979277, MAZ rs34286592, and L3MBTL3 rs4364506 were genotyped using PCR-RFLP and genotyping of ERG rs2836425 was performed by tetra-primer ARMS PCR. Our findings showed a significant difference in the allelic frequencies for the four SNPs of SHMT1 rs4925166, SHMT1 rs1979277, MAZ rs34286592, and ERG rs2836425, while there were no differences in the allele and genotype frequencies for L3MBTL3 rs4364506. These significant associations were observed for the following genotypes: TT and GG genotypes of SHMT1 rs4925166 (OR 0.47 and 1.90, respectively) genotype GG of SHMT1 rs1979277 (OR 0.63), genotype GG of MAZ rs34286592 (OR 0.61), TC and CC genotypes of ERG rs2836425 (OR 1.89 and 0.50, respectively). Our study highlighted that people who are carrying genotypes including GG (SHMT1 rs4925166) and TC (ERG rs2836425) have the highest susceptibility chance for MS, respectively. However, genotypes TT (SHMT1 rs4925166), CC (ERG rs2836425), GG (MAZ rs34286592), and GG (SHMT1 rs1979277) had the highest negative association (protective effect) with MS, respectively. L3MBTL3 rs4364506 was found neither as a predisposing nor a protective variant.

A Systematic Review of the Genotoxicity and Antigenotoxicity of Biologically Synthesized Metallic Nanomaterials: Are Green Nanoparticles Safe Enough for Clinical Marketing?

Background and objectives: Although studies have elucidated the significant biomedical potential of biogenic metallic nanoparticles (MNPs), it is very important to explore the hazards associated with the use of biogenic MNPs. Evidence indicates that genetic toxicity causes mutation, carcinogenesis, and cell death. Materials and Methods: Therefore, we systematically review original studies that investigated the genotoxic effect of biologically synthesized MNPs via in vitro and in vivo models. Articles were systematically collected by screening the literature published online in the following databases; Cochrane, Web of Science, PubMed, Scopus, Science Direct, ProQuest, and EBSCO. Results: Most of the studies were carried out on the MCF-7 cancer cell line and phytosynthesis was the general approach to MNP preparation in all studies. Fungi were the second most predominant resource applied for MNP synthesis. A total of 80.57% of the studies synthesized biogenic MNPs with sizes below 50 nm. The genotoxicity of Ag, Au, ZnO, TiO2, Se, Cu, Pt, Zn, Ag-Au, CdS, Fe3O4, Tb2O3, and Si-Ag NPs was evaluated. AgNPs, prepared in 68.79% of studies, and AuNPs, prepared in 12.76%, were the two most predominant biogenic MNPs synthesized and evaluated in the included articles. Conclusions: Although several studies reported the antigenotoxic influence of biogenic MNPs, most of them reported biogenic MNP genotoxicity at specific concentrations and with a dose or time dependence. To the best of our knowledge, this is the first study to systematically evaluate the genotoxicity of biologically synthesized MNPs and provide a valuable summary of genotoxicity data. In conclusion, our study implied that the genotoxicity of biologically synthesized MNPs varies case-by-case and highly dependent on the synthesis parameters, biological source, applied assay, etc. The gathered data are required for the translation of these nanoproducts from research laboratories to the clinical market.

TCF4 and GRM8 gene polymorphisms and risk of schizophrenia in an Iranian population: a case-control study.

TCF4 and GRM8, two significant genes involved in the normal nervous development and glutamate pathway, are thought to be involved in the pathogenesis of schizophrenia (SCZ). We aimed to explore the association of TCF4 and GRM8 gene polymorphisms with risk of SCZ. The rs8766 in TCF4 and rs712723 in GRM8 were selected for genotyping in a set of Iranian case-control samples including 215 patients and 220 matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Although rs8766 increased the OR, we found that rs8766 allele and genotype frequencies were not significantly different between case and control groups and a significant association cannot be suggested for the selected SNP. However, allele C and genotype CC (allele C: OR 1.48, 95% CI 1.13-1.94; genotype CC: OR 1.71, 95% CI 1.09-2.68) of rs712723 polymorphism was found to have a significant association with risk of SCZ. Frequency of allele C (P = 0.003) and genotype CC (P = 0.017) was higher in the schizophrenic patients, while allele T (P = 0.003) and genotype TT (P = 0.028) frequencies were found lower in patients. Our findings indicate that rs712723 in GRM8 may play an important role in the pathogenesis of SCZ. However, our conclusion needs to be confirmed in other population.

Association of VDR gene polymorphisms with risk of relapsing-remitting multiple sclerosis in an Iranian Kurdish population.

PURPOSE: The purpose of this study was to evaluate the association of VDR Apa-I, Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple sclerosis (MS) risk in an Iranian Kurdish population. MATERIALS AND METHODS: A population including of 118 patients and 124 healthy matched controls were recruited to the study. Genotyping of the SNPs was accomplished using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of allele T of Fok-I (P = 0.003) and allele C of Taq-I (P = 0.0003) was significantly different between case and control subjects and showed significant association with risk of MS (OR = 1.84, 95% CI = 1.23-2.76; OR = 1.98, 95% CI = 1.36-2.87, respectively). CT genotype (OR = 1.7, 95% CI = 1.05-2.99) of Fok-I and CC genotype (OR = 2.18, 95% CI = 1.05-4.52) of Taq-I showed a predisposing effect. Combined TT+TC vs. CC for Fok-I (OR = 2.15, 95% = CI 1.29-3.60) and combined CC+TC vs. TT for Taq-I (OR = 2.58, 95% CI 1.51-4.40) were susceptibility genotypes for MS. Apa-I and Bsm-I were not significantly associated with risk of MS (OR < 1, P > 0.05) and any genotypes in any genetic models were not significantly different between cases and controls (P > 0.05). CONCLUSION: As a result, Fok-I and Taq-I showed significant association with risk of MS, while Apa-I and Bsm-I were not observed to be related to the risk of the disease in this population.

Detection of CCND1 , C-MYC , and FGFR1 amplification using modified SYBR Green qPCR and FISH in breast cancer

Background/aim: The aims of this study were to detect CCND1 , C-MYC , and FGFR1 amplification using qPCR, confirmation with FISH, and to further assess their clinicopathological relevance. Materials and methods: Thirty-five breast tumor samples were analyzed for amplification of the selected genes using modified SYBR Green qPCR. The accuracy of the qPCR was assessed by FISH as a gold-standard method. Results: CCND1 , C-MYC , and FGFR1 amplifications were observed in 34.28%, 28.57%, and 17.14% of the 35 samples, respectively. qPCR results were significantly confirmed by FISH and qPCR and FISH showed excellent correlation (P = 0.000). CCND1 amplification with tumor stage (P = 0.044), positive metastatic status (P = 0.042), positive family history (P = 0.042), and C-MYC status (P = 0.005); C-MYC amplification with tumor size (P = 0.021), tumor grade (P = 0.018), tumor stage (P = 0.032), and FGFR1 status (P < 0.000); and FGFR1 amplification with tumor size (P = 0.041) and positive ER status (P = 0.042) were statistically associated. Conclusion: Our findings revealed that the applied qPCR approach could precisely quantify the relative gene copy number. More studies with a larger sample size are suggested to confirm the clinicopathological value of CCND1 , C-MYC , and FGFR1 amplification.

An Effective Concentration of 5-Aza-CdR to Induce Cell Death and Apoptosis in Human Pancreatic Cancer Cell Line through Reactivating RASSF1A and Up-Regulation of Bax Genes.

BACKGROUND: Promoter hyper-methylation of tumor suppressor genes is a common event that occurs in cancer. As methylation is a reversible modification, agents capable of reversing an abnormal methylation status should help to combat cancer. 5-Aza-CdR is a DNA methyl-transferase inhibitor. The present study aimed to evaluate the effect of 5-Aza-CdR on the proliferation of human pancreatic cancer cell line (PANC-1) and the expression of RASSF1A and Bax genes. METHODS: PANC-1 cells were cultured and treated with 5 and 10 µM/L of 5-Aza-CdR for 24, 48, 72, and 96 hours and the percentages of cell viability and apoptosis were measured by MTT and flow cytometry. RASSF1A gene promoter methylation was assessed by methyl-specific primer-PCR (MSP-PCR) and the expression of RASSF1A and Bax genes was measured using quantitative real-time PCR (qPCR). All quantitative data are presented as mean±SD (standard deviation). The one-way analysis of variance (ANOVA) with the LSD post hoc test was performed for statistical analysis using the SPSS software package, version 16.0. RESULTS: 3-[4,5-dimethythiaziazol-2yl]-2,5-diphenyl tetrazoliumbr omide (MTT) assay revealed that 5-Aza-CdR significantly inhibit the growth and proliferation of PANC-1. The flow cytometry results showed over 40% and 70% of early and late apoptotic cells after treatment with 5 and 10 µm/L of 5-Aza-CdR, respectively. MSP-PCR data indicated that the treatment of cells with 10 µm/L 5-Aza-CdR resulted in partial demethylation of RASSF1A gene promoter. qPCR results showed significant re-expression of RASSF1A and up-regulation of Bax genes after 96 hours treatment of cells with 10 µm/L 5-Aza-CdR versus control cells (P<0.01). CONCLUSION: The result demonstrated that 5 and 10 µM of 5-Aza-CdR induce cell death and apoptosis by epigenetic reactivation of RASSF1A and up-regulation of Bax genes.

Association of transcription factor 4 (TCF4) gene mRNA level with schizophrenia, its psychopathology, intelligence and cognitive impairments.

Schizophrenia (SCZ), is considered as one of the most debilitating mental disorders around the world. Symptom-based clinical interview and numerous tests have been used to evaluate the diagnosis and also cognitive disturbances in patients with SCZ. All these tests measure phenotype-based functions. Thus, it seems accurate diagnosis of such complex disorders must rely on more valid and reliable factors. In this study, we evaluated the association of transcription factor 4 (TCF4) gene mRNA level in peripheral blood with SCZ, and also its psychopathology, cognitive and intellectual impairments. In this study, using real-time PCR, we compared TCF4 mRNA level between the case (70 unmedicated schizophrenia patients) and healthy control (n = 72) groups. In addition, all subjects underwent Psychopathology (PANSS) and cognitive and intelligence (WAIS, WMS, Stroop, WCST) assessments, and scores were compared between the two groups. Also, to determine the effect of TCF4 expression on psychopathology, cognitive and intellectual functions, the correlation between expression level and test scores was measured. The correlation between gene expression and age of onset and duration of the disorder was evaluated as well. Our results showed that the TCF4 mRNA level, psychopathology, cognitive and intellectual functions were significantly different in all, male, and female patients compared to healthy participants. Additionally, it was found that TCF4 level is positively correlated with scores of WAIS and WMS and is negatively correlated with Stroop and WCST errors and PANSS score. Our results showed that the mRNA level of TCF4 may be associated with SCZ, its psychopathology, IQ and cognitive impairments in an Iranian group of patients with SCZ. These results may help to better understanding the TCF4 role in the psychopathogenesis of SCZ and also may shed some light on the ongoing works conducted on peripheral biomarker-based diagnosis of complicated mental disorders.

Inflammatory and genomic interactions within keratoconus susceptible patients: a nationwide registered case-control study.

PURPOSE: This study aimed to investigate the association between variants in the interleukin (IL)-1 gene cluster and susceptibility to keratoconus (KC) in an Iranian population. METHODS: In the case group, there were 188 KC patients diagnosed by clinical findings and corneal tomography. The control group included all 205 healthy controls with no personal or family history of eye-related, metabolic, or immune system-related disease. Using the standard salting out extraction procedure, genomic DNA was isolated from peripheral blood leukocytes. The genotypes were determined by applying agarose gel electrophoresis for the IL-1RN 86 bp VNTR and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rs16944 and rs1143634. RESULTS: The results showed a significant association between the IL-1ß rs1143634 (rs1143634 T allele, P = 0.008) and IL-1RN 86 bp VNTR polymorphisms (LL and LS genotype, P = 0.048 and 0.012 respectively) and susceptibility to KC in the Iranian population. The genotype distributions of rs1143634 (P = 0.004) and rs2234663 (P = 0.042) significantly differed between case and control groups, with certain genotypes demonstrating a protective effect against KC. Logistic regression analysis revealed a protective effect of the IL-1RN L allele [odds ratio (OR) = 0.367, 95% confidence interval (CI): 0.240-0.562; P = 0.000] and certain haplotypes (OR = 0.628, 95% CI: 0.447-0.884; P = 0.007) against KC. However, no significant association was found for the IL-1ß rs16944 polymorphism. CONCLUSION: This study provides evidence for an association between variants in the IL-1 gene cluster and susceptibility to KC in an Iranian population. Further research on larger and more diverse populations is warranted to validate these findings and explore the underlying mechanisms involved.

Evaluating Gene Expression and Methylation Profiles of TCF4, MBP, and EGR1 in Peripheral Blood of Drug-Free Patients with Schizophrenia: Correlations with Psychopathology, Intelligence, and Cognitive Impairment.

Discovery and validation of new, reliable diagnostic and predictive biomarkers for schizophrenia (SCZ) are an ongoing effort. Here, we assessed the mRNA expression and DNA methylation of the TCF4, MBP, and EGR1 genes in the blood of patients with SCZ and evaluated their relationships to psychopathology and cognitive impairments. Quantitative real-time PCR and quantitative methylation-specific PCR methods were used to assess the expression level and promoter DNA methylation status of these genes in 70 drug-free SCZ patients and 72 healthy controls. The correlation of molecular changes with psychopathology and cognitive performance of participants was evaluated. We observed downregulation of TCF4 and upregulation of MBP mRNA levels in SCZ cases, relative to controls in our study. DNA methylation status at the promoter region of TCF4 demonstrated an altered pattern in SCZ as well. Additionally, TCF4 mRNA levels were inversely correlated with PANSS and Stroop total errors and positively correlated with WAIS total score and working memory, consistent with previous studies by our group. In contrast, MBP mRNA level was significantly positively correlated with PANSS and Stroop total errors and inversely correlated with WAIS total score and working memory. These epigenetic and expression signatures can help to assemble a peripheral biomarker-based diagnostic panel for SCZ.

A meta-analysis of the association of ApaI, BsmI, FokI, and TaqI polymorphisms in the vitamin D receptor gene with the risk of polycystic ovary syndrome in the Eastern Mediterranean Regional Office population.

Background: The results of case-control studies on the association between vitamin D receptor gene (VDR) polymorphisms and polycystic ovary syndrome (PCOS) are inconclusive. Objective: We aimed to more precisely evaluate the correlation between the ApaI, BsmI, FokI, and TaqI VDR gene polymorphisms and PCOS susceptibility. Materials and Methods: PubMed, Scopus, Science Citation Index, and Google Scholar databases were searched to retrieve related reports released up to the end of 2020. To evaluate the association strength of the VDR gene polymorphisms with PCOS risk, pooled odds ratios (OR) with a 95% confidence interval were determined. Results: In total, 1,119 subjects (560 PCOS cases and 559 controls) from 7 studies were included which met the inclusion criteria. A statistically significant association between the TaqI polymorphism and PCOS susceptibility was found in the Eastern Mediterranean Regional Office population (T vs. t: OR = 0.715; TT vs. tt: OR = 0.435, p < 0.001; TT vs. Tt+tt: OR = 0.696, p = 0.01; tt vs. TT+Tt: OR = 1.791, p < 0.001). It was found that the ApaI variant was a risk factor in the dominant inheritance model (AA vs. Aa+aa: OR = 1.466, p = 0.01) and the FokI polymorphism was a protective factor in the recessive inheritance model (ff vs. FF+Ff: OR = 0.669, p = 0.04). The VDR BsmI polymorphism did not show association with PCOS susceptibility. Conclusion: Our meta-analysis revealed that the VDR ApaI in the dominant model, VDR FokI in the recessive model, and VDR TaqI polymorphisms in all genetic models are associated with vulnerability to PCOS. However, further studies with a larger sample size are required.

Combination therapy of cisplatin and resveratrol to induce cellular aging in gastric cancer cells: Focusing on oxidative stress, and cell cycle arrest.

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease's high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested. Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest. Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol. Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.

Kidney diseases and COVID-19 infection: causes and effect, supportive therapeutics and nutritional perspectives.

Recently, the novel coronavirus disease 2019 (COVID-19), has attracted the attention of scientists where it has a high mortality rate among older adults and individuals suffering from chronic diseases, such as chronic kidney diseases (CKD). It is important to elucidate molecular mechanisms by which COVID-19 affects the kidneys and accordingly develop proper nutritional and pharmacological strategies. Although numerous studies have recently recommended several approaches for the management of COVID-19 in CKD, its impact on patients with renal diseases remains the biggest challenge worldwide. In this paper, we review the most recent evidence regarding causality, potential nutritional supplements, therapeutic options, and management of COVID-19 infection in vulnerable individuals and patients with CKD. To date, there is no effective treatment for COVID-19-induced kidney dysfunction, and current treatments are yet limited to anti-inflammatory (e.g. ibuprofen) and anti-viral medications (e.g. Remdesivir, and Chloroquine/Hydroxychloroquine) that may increase the chance of treatment. In conclusion, the knowledge about kidney damage in COVID-19 is very limited, and this review improves our ability to introduce novel approaches for future clinical trials for this contiguous disease.

Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients.

INTRODUCTION: Growing evidence documented the critical impacts of vitamin D (VD) in the prognosis of COVID-19 patients. The functions of VD are dependent on the vitamin D receptor (VDR) in the VD/VDR signaling pathway. Therefore, we aimed to assess the association of VDR gene polymorphisms with COVID-19 outcomes. METHODS: In the present study, eight VDR single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 500 COVID-19 patients in Iran, including 160 asymptomatic, 250 mild/moderate, and 90 severe/critical cases. The association of these polymorphisms with severity, clinical outcomes, and comorbidities were evaluated through the calculation of the Odds ratio (OR). RESULTS: Interestingly, significant associations were disclosed for some of the SNP-related alleles and/or genotypes in one or more genetic models with different clinical data in COVID-19 patients. Significant association of VDR-SNPs with signs, symptoms, and comorbidities was as follows: ApaI with shortness of breath (P ˂ 0.001) and asthma (P = 0.034) in severe/critical patients (group III); BsmI with chronic renal disease (P = 0.010) in mild/moderate patients (group II); Tru9I with vomiting (P = 0.031), shortness of breath (P = 0.04), and hypertension (P = 0.030); FokI with fever and hypertension (P = 0.027) in severe/critical patients (group III); CDX2 with shortness of breath (P = 0.022), hypertension (P = 0.036), and diabetes (P = 0.042) in severe/critical patients (group III); EcoRV with diabetes (P ˂ 0.001 and P = 0.045 in mild/moderate patients (group II) and severe/critical patients (group III), respectively). However, the association of VDR TaqI and BglI polymorphisms with clinical symptoms and comorbidities in COVID-19 patients was not significant. CONCLUSION: VDR gene polymorphisms might play critical roles in the vulnerability to infection and severity of COVID-19, probably by altering the risk of comorbidities. However, these results require further validation in larger studies with different ethnicities and geographical regions.