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Background. Chronic kidney disease (CKD) is defined by gradual deterioration of renal parenchyma and decline of functioning nephrons. The risk of cardiovascular events is drastically increased in patients with CKD. This complicated link of CKD and cardiovascular disease (CVD) is not well understood till date. Objective. We aim to study the influence of genetic variants of matrix Gla protein (MGP) gene rs1800801, rs1800802, and rs4236 and nitric oxide synthase-3 (NOS3) gene rs1799983 and rs2070744 on the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils. Methods. One hundred and eighty-five CKD patients and 185 controls were recruited in this research. Flow-mediated dilatation (FMD) of brachial artery was measured ultrasonically. Circulating levels of MGP and nitric oxide (NO) were measured by ELISA. Genotyping was done by real-time PCR. Results. We observed a significant difference in the distribution of TT and CT genotypes of NOS3 (rs2070744), indicating an increase in the risk of CKD. NO level was significantly decreased in CKD cases than controls. We also found a significant difference in the distribution of TTA and CCG haplotypes of MGP polymorphisms (1-rs4236; 2-rs1800801; 3-rs1800802) between the groups, indicating an increase in the risk of CKD. CT genotype of MGP (rs4236) and CT genotype of NOS3 (rs2070744) variants were found to be associated with decreased FMD, indicating endothelial dysfunction, the harbinger of CVD. Conclusion. We conclude that genetic variants of MGP and NOS3 enhance the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils.

Background: Chronic kidney disease (CKD) is defined by gradual deterioration of renal parenchyma and decline of functioning nephrons. The risk of cardiovascular events is drastically increased in patients with CKD. This complicated link of CKD and cardiovascular disease (CVD) is not well understood till date., Objective: We aim to study the influence of genetic variants of matrix Gla protein ( MGP ) gene rs1800801, rs1800802, and rs4236 and nitric oxide synthase-3 ( NOS3 ) gene rs1799983 and rs2070744 on the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils., Methods: One hundred and eighty-five CKD patients and 185 controls were recruited in this research. Flow-mediated dilatation (FMD) of brachial artery was measured ultrasonically. Circulating levels of MGP and nitric oxide (NO) were measured by ELISA. Genotyping was done by real-time PCR., Results: We observed a significant difference in the distribution of TT and CT genotypes of NOS3 (rs2070744), indicating an increase in the risk of CKD. NO level was significantly decreased in CKD cases than controls. We also found a significant difference in the distribution of TTA and CCG haplotypes of MGP polymorphisms (1-rs4236; 2-rs1800801; 3-rs1800802) between the groups, indicating an increase in the risk of CKD. CT genotype of MGP (rs4236) and CT genotype of NOS3 (rs2070744) variants were found to be associated with decreased FMD, indicating endothelial dysfunction, the harbinger of CVD., Conclusion: We conclude that genetic variants of MGP and NOS3 enhance the risk of CKD and its associated cardiovascular comorbidity in South Indian Tamils., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 G. Priyadarshini et al.)

Background Chronic kidney disease (CKD) leads to a progressive decline in renal function, primarily due to deteriorating kidney structures. Vascular calcification is a key effect of CKD. MicroRNAs (miRNAs) play a significant role in the onset and progression of both cardiovascular illness and CKD. Aim The aim of this study was to compare biomarkers of endothelial dysfunction, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), miRNA 155, and miRNA 145, in patients with CKD versus controls. Methods We recruited 60 patients with CKD and 60 controls. All participants underwent brachial artery flow-mediated dilatation (FMD). Asymmetric dimethylarginine (ADMA) levels were measured using ELISA. Levels of miRNA 145 and miRNA 155 were quantified using real-time polymerase chain reaction (PCR). Results Serum levels of miRNA 145, miRNA 155, 25(OH)D, and FMD were significantly lower in CKD patients compared to controls. Conversely, serum ADMA and iPTH levels were significantly higher in CKD patients. There was a significant negative association between miRNA 145, miRNA 155, FMD, and 25(OH)D with ADMA and iPTH. Additionally, miRNA 145, miRNA 155, FMD, and 25(OH)D showed a significant positive correlation with estimated glomerular filtration rate (eGFR) and with each other. Conclusion Lower levels of miRNA 145 and miRNA 155 and increased endothelial dysfunction correlate with CKD severity, suggesting an accelerated risk for cardiovascular disease (CVD)., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. JIPMER Institutional Ethics Committee issued approval JIP/IEC/2019/391. This study was conducted in concordance with the Indian Council of Medical Research (ICMR) Ethical Guidelines for Biomedical Research involving Human Participants, 2017. Informed consent was obtained from all individual participants included in the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Medha Rajappa declare(s) a grant from Jawaharlal Institute of Postgraduate Medical Education and Research. The present study was funded by the JIPMER Intramural Research Grant (Grant number: JIP/Res/Intramural/Phs2/2019-20). Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kumar et al.)

Objective: Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic events within signal transduction pathways governing normal cellular physiology are quantitatively or qualitatively altered. There are various molecular targets like Cyclin D and PI3k- alpha Ras Binding Domain receptor protein involved in the pathogenesis of Oral Squamous Cell Carcinoma. The aim of the study is to demonstrate the computer aided drug design to identify a potent natural molecule for targeting cyclin D4 and PI3K RAS binding protein., Materials and Methods: Target selection (Cyclin D1 and PI3K-alpha Ras Binding Domain receptor) was done and structures were derived from protein data bank. Ligands (Apigenin, Chrysoeriol and Luteolin) selection was done and structure derived. Final docking was performed by Autodock., Results: From the docking results it can be seen that luteolin has the highest binding energy (-5.45) with the Cyclin D receptor molecule followed by Chrysoeriol (-4.99) and Apigenin (-4.96). The binding energies of the ligands against PI3K-alpha Ras Binding Domain receptors were Apigenin (-4.51), Chrysoeriol (-4.6) and Luteolin (-4.56)., Conclusion: The study concludes that all the three selected ligands possess high binding energy with both the target proteins involved in carcinogenesis with highest binding energy possessed by Luteolin against the Cyclin D receptor and by Chrysoeriol against PI3K-RAS binding protein. Thus their activity can be utilized to derive potential Anti-cancer therapeutic drugs.