Association study between genetic polymorphisms in MTHFR and stroke susceptibility in Egyptian population: a case-control study.

Stroke is a major global disability cause, and genetic variables for multifactorial illnesses like stroke are crucial for precision medicine. The purpose of this study is to see if genetic variants in the MTHFR gene are associated with a higher risk of ischemic stroke among the Egyptian population. A case-control study was conducted at Mansoura University Hospital, involving 100 stroke patients and 150 healthy volunteers as the control group. Peripheral blood genomic DNA was isolated and single-nucleotide polymorphisms were genotyped using ARMS-PCR. The CT and TT genotypes of the C677T gene polymorphism exhibited substantial risks for having stroke disease [(OR 3.856; P ≤ 0.001); (OR 4.026; P ≤ 0.001), respectively]. The T allele was significantly more prevalent among patients compared to controls. (OR 2.517; (P = 0.001)). The over-dominant and dominant models demonstrated a substantial relationship between stroke groups at risk of developing stroke but not the Recessive model. An extensive connection was found between the MTHFR A1298C and stroke danger in three different inheritance models: dominant (CC + CA vs. AA), over-dominant (AA + CC vs AC), and allelic (C allele) (P < 0.001). A highly significant difference in blood pressure, total cholesterol, and triglycerides levels was found between patients and control. While there was no meaningful link discovered between genetic polymorphism with SBP, DBP, TG, LDL, VLDL among stroke group (P > 0.05 for each) except the CC genotype that was significantly associated with lower levels of TC and HDL when compared to CT + TT genotypes. The study evaluates a strong link among MTHFR mutations in genes and the probability to get stroke. The research significantly supports the use of MTHFR ((rs1801133) and (rs1801131) variations in stroke prediction.

Detection of EGFR gene polymorphisms in non-small cell lung cancer Egyptian patients: a case-control study.

BACKGROUND: Non-Small Cell Lung Cancer displays several genetic mutations including epidermal growth factor receptor. This study's objective was to determine if the EGFR exon19 rs121913438 and exon21 rs121434568 variations play a role in NSCLC susceptibility. METHODS: Case-control research was done at the Mansoura university oncology center including 124 NSCLC patients, and 124 healthy volunteers. blood was used to obtain genomic DNA. ARMS-PCR was used to genotype single-nucleotide polymorphisms. RESULTS: Molecular study for EGFR exon 19 del. showed NSCLC cases were significantly associated with a higher proportion of heterozygous WD, WD + DD dominant genotypes, and mutant D allele, (p < 0.05 for each), with a risk to develop NSCLC. also, NSCLC cases were significantly associated with a higher proportion of heterozygous TG, TG + GG dominant genotype, G mutant allele, (p < 0.05 for each), with a risk to develop LC (OR > 1 for each). regarding the two EGFR mutations, TTF1 staining was significantly associated with WD + DD genotypes for EGFR exon 19 del But not EGFR exon 21. No substantial differences were found among all studied cases with CK7 or napsin A Tumor cytochemistry. CONCLUSIONS: The WD heterozygous genotype and D allele in exon 19 del. mutation as well as the TG heterozygous and G allele in exon 21 substitution mutation in EGFR gene are strongly associated with the development of advanced-NSCLC in the Egyptians.

Association of A1AT genetic polymorphism and NSCLC: a case- control study in Egyptian population.

BACKGROUND: Lung cancer mortality is higher than other forms of cancer. Genetic tendencies in cancer patients have long been known. Given the link between A1ATD and numerous lung disorders, it is worth investigating if this genetic trait is linked to a higher risk of developing LC, as the lung is the most afflicted organ in individuals with severe A1ATD. This study is intended to investigate the possible association between AAT rs17580 and rs8004738 gene polymorphisms and susceptibility to non-small cell lung cancer for early prediction in Egyptians. METHODS: A case-control study was performed on 124 NSCLC cases and 124 healthy controls from 2021 to 2022 in the oncology center of Mansoura University. Peripheral blood was used to obtain genomic DNA. ARMS-PCR was used to genotype SNPs and other chemical parameters. Windows SPSS Statistics was used to review, encode, and tabulate the acquired data. RESULTS: A molecular study for A1AT rs17580 and rs8004738 genotypes showed that NSCLC cases were significantly associated with a higher proportion of mutant S (T) and mutant Z (A) alleles (p = 0.042, 0.041, respectively). Different A1AT genotypes (MS, MZ, SS, SZ, and ZZ) showed no significant association with NSCLC or NLR. CONCLUSION: S and Z alleles might have significant impacts on NSCLC risk and can be useful for detecting and protecting individuals who may be vulnerable to carcinogens. Further research with larger sample sizes is needed to confirm the current findings.

Hormonal and molecular characterization of calcium oxalate stone formers predicting occurrence and recurrence.

The purpose of the study is to investigate the role of sex hormones, androgen receptors (ARs) and miRNA/CSF-1 in occurrence and recurrence of calcium oxalate (CaOx) renal urolithiasis. In this prospective study, 74 patients with CaOx stones; stone formers group (SFG) and 40 healthy subjects; control group were compared. SFG includes both de novo and recurrent cases. Steroid sex hormone plasma assay including testosterone, free testosterone, dihydrotestosterone, estradiol, and sex hormone binding globulin was analyzed. ARs, miRNA-185-5p and CSF-1 expression were compared between the groups. SFG showed significant higher ARs and miRNA-185-5p expression (3.7 ± 1.3, 1.8 ± 0.4, respectively) than control group (1 ± 0.08 and 1 ± 0.07, respectively) (p < 0.05). However, CSF-1 expression was significantly lower in stone formers than control group (0.4 ± 0.19 vs 1 ± 0.1, respectively) (p < 0.05). No differences were detected between de novo and recurrent SFG regarding sex hormones, AR, miRNA or CSF-1 expression. Our data suggest the important role of AR, miRNA and CSF-1 signaling in human nephrolithiasis pathogenesis.

Analysis of the association of NPHS2 and ACTN4 genes polymorphism with nephrotic syndrome in Egyptian children.

BACKGROUND: One of the most common kidney illnesses in developing countries is pediatric nephrotic syndrome (PNS), which is frequently associated with dyslipidemia and edema. The rapid discovery of genes related to NS has aided in the understanding of the molecular mechanics of glomerular filtration. The goal of this study is to determine the relationship between NPHS2 and ACTN4 in PNS youngsters. METHODS: A study with 100 NS children and 100 healthy matched volunteers was conducted. Genomic DNA was extracted from peripheral blood. Single-nucleotide polymorphisms were genotyped using ARMS-PCR. RESULTS: A substantial decline in the level of albumin was found in NS cases (P < 0.001) Further on, a significantly difference in T.C and TG level between healthy and NS patient. Molecular study showed a highly significant difference of NS patients from controls regarding NPHS2 rs3829795 polymorphic genotypes as the GA heterozygous genotype shows highly significant difference from controls (P < 0.001) as well as GA + AA genotypes (P < 0.001) in comparison with GG genotype. Regarding rs2274625, The GA heterozygous genotype showed no statistically significant difference between genotypes and alleles with NS (P = 0.246). Association of AG haplotype NPHS2 rs3829795-rs2274625 haplotypes found a significant association with the risk of developing NS (P = 0.008). Concerning the ACTN4 rs121908415 SNP, there was no link between this mutation and NS children. CONCLUSION: The correlation of AG haplotype NPHS2 rs3829795-rs2274625 haplotypes identified a strong association with the likelihood of getting NS, according to our findings. There was no connection found between the ACTN4 rs121908415 SNP and NS children.

Gene expression analysis and the risk of relapse in favorable histology Wilms' tumor.

Introduction and Objectives: Wilms' tumor (WT) relapse occurs in 15% of patients. We aim to investigate the association between the expression of several genetic markers and WT relapse risk. Materials and methods: The study included 51 children treated for WT at a tertiary center between 2001 and 2019: 23 patients had disease relapse (group A) and 28 remained relapse-free after at least 2 years of follow-up (group B). Patients with syndromic, bilateral synchronous or anaplastic WT were excluded. Autologous renal tissue from 20 patients served as control. Total RNA was isolated from tumor tissue and control. Gene expression levels of WT1, HIF1α, b-FGF, c-MYC and SLC22A18 were assessed using quantitative RT-PCR and normalized to GAPDH. Immunohistochemical staining for WT1 and gene expression levels were compared between the study groups. Results: Median patient age was 3 (IQR = 2-5) years and 36 (70.6%) had stage I disease. Baseline characteristics were similar between study groups. Relapse occurred at a median of 6.8 (2.8-24.7) months, predominantly in the lungs (11/23, 47.8%). Tumors that relapsed expressed significantly higher levels of WT1, HIF1α, b-FGF and c-MYC and lower levels of SLC22A18 (p < 0.001). Strong immunohistochemical staining for WT1 was seen in 73.9% of group A and 14.29% of group B (p < 0.001). These associations retained statistical significance irrespective of patient and tumor characteristics. Conclusions: Higher expression levels of WT1, HIF1 α, b-FGF and c-MYC and lower level of SLC22A18 are associated with increased risk of WT relapse. These genetic markers can serve as future prognostic predictors and help stratify patients for treatment.

Identification of 100 KDa protein in sera of mice-treated with Cu(II) complex with superoxide dismutase-mimetic activity.

The protein profile of sera isolated from mice pre-treated with Cu(II) complex of Girard T with superoxide dismutase (SOD)-mimetic activity was analyzed using SDS-PAGE. This complex was intraperitoneally administered (10 mg/Kg body weight) to Swiss albino mice. The resolved polypeptides showed a new sharp band at 100 KDa against which a polyclonal antibody was raised in rabbit. Sera of rabbit anti-100 KDa protein was used as a powerful probe for the detection of 100 KDa protein isolated from sera of treated mice. Western blot assays revealed a strong reactive polypeptide band at 100 KDa in sera of the mice, but no cross reaction was observed with sera of normal mice. The identification of purified polypeptide was confirmed by different characterization experiments.

2-Methylaminopyridine-copper (II) complex catalyzes protein degradation.

To investigate the mechanism of scission of proteins by the chemical cleaving agents like metal complexes, bovine serum albumin (BSA) has been treated by the copper(II) complex CuL2SO4, where L is 2-methylaminopyridine. BSA degradation increased with increasing the concentration of the copper complex. Copper complex rapidly degraded BSA at mild acidic and neutral pH values while no degradation occurred at alkaline pH values. Moreover, the degradation was increased at higher temperatures. Copper complex act as a catalyst for the polypeptide hydrolysis. The protein degradation was protected with beta-mercaptoethanol by acting as radical scavenger. H2O2 increased BSA degradation which is apparent by the disappearance of the original band. H2O2 reacts with copper complex to produce a reactive oxygen species (ROS), such as hydroxyl radical or a metal-coordinated oxo or peroxo species, which in turn can initiate cleavage of the peptide backbone nearby.