Expression of DDSR1 Long Non-Coding RNA and Genes Involved in the DNA Damage Response in Sperm with DNA Fragmentation.

The molecular mechanism responsible for sperm DNA fragmentation is not fully understood. Therefore, identifying genes related to the response to DNA damage is an important area of research. Recently, the role of long non-coding RNAs (LncRNAs), especially DNA damage-sensitive RNA1 (DDSR1) in male infertility has been highlighted. In this research, a protein-protein interaction network (PPIN) was constructed using the STRING database, and functional classification was conducted using webgestalt servers. Subsequently, a group of 40 males with a high degree of sperm DNA fragmentation (DFI ≥ 25%) was compared to a control group of 20 healthy males with a normal sperm DNA fragmentation rate (DFI < 25%). To assess gene expression, real-time polymerase chain reaction (PCR) analysis was performed on DNA samples obtained from both healthy and infertile males. Our findings revealed that infertile men with an abnormal DFI index showed significantly lower expression levels of the long noncoding RNA DDSR1, as well as the genes BRCA1, MRE11A, RAD51, and NBN, compared to the control group. Pathway analysis of the network proteins using Reactome indicated involvement in crucial cellular processes such as the cell cycle, DNA repair, meiosis, reproduction, and extension of telomeres. In conclusion, the downregulation of LncRNA and genes associated with the DNA damage response in males with an abnormal DFI suggests that these factors may contribute to the development of sperm DNA fragmentation and could potentially serve as diagnostic markers for further investigation in therapeutic interventions in the future.

Evaluation of Immunohistochemical Expression of Survivin and its Correlation with qRT-PCR Results as a Useful Diagnostic Marker in Gastric Cancer.

Background: Today, survivin is known as one of the most specific cancer proteins; provide unique and practical study opportunities. Clinical value of survivin in gastric cancer (GC) is not yet appointed. To establish the expression level of survivin and its diagnosis value in Iranian patients with GC, we evaluated the association of survivin expression with clinicopathologic factors. Methods: Overall, 60 matched-normal controls with 60 GC samples including 30 cases with evidence of metastasis at time of our study and 30 cases without evidence of metastasis were recruited, in Tehran, Iran during 2008 to 2018. Survivin expression was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) study. Results: Increased expression of survivin at mRNA and protein levels was found in 86.7% and 71.6% of cases, respectively. Evidence indicated a significant difference in survivin mRNA expression level between tumor and nontumoral (marginal) tissues (P<0.001). The difference in expression of survivin mRNA was not significant between metastatic and non-metastatic tumor tissues (P=0.171). Positive immunoreactivity of survivin was observed to be predominantly in the nucleus of tumor cells. A significant difference in survivin protein expression was detected between tumor and non-tumoral tissues (P<0.001) and between metastatic and non-metastatic tumor tissues (P<0.001). There was no significant association between survivin mRNA expression and clinicopathological variables. However, survivin protein expression was significantly correlated with perineural involvement (P<0.018). Conclusion: This data could be supportive of using survivin as a useful diagnostic marker in GC. Although, more research is needed in this area.

Association Between the G82S Polymorphism of the Receptor Gene for Advanced Glycation End-products and Soluble Serum Levels RAGE with Diabetic Nephropathy in the White (Asian) Race.

INTRODUCTION: Diabetic nephropathy is one of the most common severe symptoms of diabetes mellitus. Hyperglycemia can lead to tissue damage and inflammation due to mediators such as receptor for advanced glycation end-products (RAGE). Therefore, in this study, we aimed to investigate the association between the G82S polymorphism of the RAGE gene and diabetic nephropathy in diabetic patients. METHODS: In this case-control study, 356 participants (158 men and 198 women) of Asian race, aged 45 to 65 years, who were diagnosed with type 2 diabetes mellitus based on their fasting plasma glucose levels were enrolled. DNA was isolated from the participants' blood samples and genotyped using TETRA -Primer ARMS-PCR. Serum protein concentration of soluble RAGE (sRAGE) was also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Although we found differences in genotyping of participants between homozygous AA and GG and heterozygous GA in the studied groups, the differences were not significant (P = .568). In addition, we found no significant correlation between the G82S polymorphism of RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared with diabetic patients (P > .05). CONCLUSION: The results of this study indicate no significant association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared to diabetic patients without nephropathy. Therefore, the study suggests that there is probably no association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. DOI: 10.52547/ijkd.7872.

Novel pathogenic variant in MED12 causing non-syndromic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death and heart failure. Up to 50% of all DCM cases have a genetic background, with variants in over 250 genes reported in association with DCM. Whole-exome sequencing (WES) is a powerful tool to identify variants underlying genetic cardiomyopathies. Via WES, we sought to identify DCM causes in a family with 2 affected patients. METHODS: WES was performed on the affected members of an Iranian family to identify the genetic etiology of DCM. The candidate variant was segregated via polymerase chain reaction and Sanger sequencing. Computational modeling and protein-protein docking were performed to survey the impact of the variant on the structure and function of the protein. RESULTS: A novel single-nucleotide substitution (G > A) in exon 9 of MED12, c.1249G > A: p.Val417Ile, NM_005120.3, was identified. The c.1249G > A variant was validated in the family. Bioinformatic analysis and computational modeling confirmed that c.1249G > A was the pathogenic variant responsible for the DCM phenotype. CONCLUSION: We detected a novel DCM-causing variant in MED12 using WES. The variant in MED12 may decrease binding to cyclin-dependent kinase 8 (CDK8), affect its activation, and cause alterations in calcium-handling gene expression in the heart, leading to DCM.