Association of a single-nucleotide polymorphism in C12orf43 region with the risk of coronary artery disease.

The genetics of organisms play a vital role in the development of coronary artery disease (CAD), with its heritability estimated at approximately 50-60%. For this purpose, we examined the relationship between CAD risk and C12orf43/rs2258287 polymorphisms in the Pakistani population. In this study based on the genetic approach to dyslipidemia, a total of 200 subjects were included from the southern Punjab. The biochemical analysis of parameters (total cholesterol, triglycerides, blood glucose, high-density lipoprotein, and low-density lipoprotein) was carried out along with molecular analysis using an ARMS-PCR-based assay for single-nucleotide polymorphism (SNP) C12orf43/rs2258287 to identify the genotype. Genotypes showed a substantial correlation with both family history and metabolic markers. The cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides and blood glucose levels were higher while the high-density lipoprotein cholesterol (HDL-C) level was lower significantly (p<0.05) in cases than in controls. Age, pulse rate, diabetes, physical activity, smoking, family history, and dietary habits were also significantly associated (p<0.05) with CAD individuals. The SNP C12orf43/rs2258287 also showed an association with CAD in the population of southern Punjab. Based upon this study, it could be concluded that CAD is characterized by an unfavorable lipid profile in association with SNP C12orf43/rs2258287.

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.

BACKGROUND: The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods. METHODS: PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations. RESULTS: The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity. CONCLUSIONS: This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.

Evaluation of the potential of two halophytes to extract Cd and Zn from contaminated saltwater.

The contamination of saltwater by toxic heavy metals has become a worldwide problem. The application of phytoextraction to remove these pollutants seems to be more efficient and cheaper compared to physicochemical methods. In this work, we evaluated the potential of two halophyte species to accumulate cadmium and zinc from contaminated water. Seedlings of Carpobrotus edulis L. and Sesuvium portulacastrum L. were cultivated during 1 month on pots filled with saltwater (200 mM NaCl) containing different concentrations of Cd2+ (0, 50, 100 µM) and of Zn2+ (0, 200, and 400 µM) applied separately. Results showed that both halophytes were more resistant to Zn2+ than Cd2+ and that Sesuvium better tolerates the two metals. Zn2+ and Cd2+ concentrations in the shoot as well as the values of translocation factors suggest that these species are able to absorb and to concentrate Cd2+ and Zn2+ in their roots and shoots. Hence, after 1 month of culture on 50 µM Cd2+, plants were able to extract 31% and 21% of Cd, respectively, in S. portulacastrum and C. edulis. The Zn-extraction efficiency was less important and reached 18 and 19%, respectively, in S. portulacastrum and C. edulis cultivated under 200 µM Zn2+. Given together, data demonstrate the efficiency of the use of halophytes, especially S. portulacastrum, to extract Zn2+ and Cd2+ from salt wastewater.

Comprehensive Molecular Evaluation of HNF-1 Alpha, miR-27a, and miR-146 Gene Variants and Their Link with Predisposition and Progression in Type 2 Diabetes Patients.

BACKGROUND: Type 2 diabetes (T2D) is a metabolic condition induced by insulin resistance and pancreatic beta cell dysfunction. MicroRNAs (miRNAs) have biological significance because they regulate processes such as the molecular signaling pathways involved in the pathophysiology of diabetes mellitus. The hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a transcription factor found in hepatocytes and the pancreas. Mutations in the HNF-1 alpha gene were reportedly associated with maturity-onset diabetes of the young (MODY). The objective of the present study was to examine the associations between MiR-27a, MiR-146, and HNF-1 alpha single-nucleotide variations (SNVs) with T2D risk in the Saudi population. METHODOLOGY: We evaluated the association of SNVs of miR-27a rs895819 A>G, 146a-rs2910164 C>G, and HNF-1 alpha rs1169288 G>T (I27L) with the risk of T2D in Saudi patients with the Amplification Refractory Mutation System PCR (ARMS-PCR). For the miR-27a SNVs, we used 115 cases (82 males, 33 females) and 117 matched healthy controls (HCs); for the Mir-146 SNVs, we used 103 cases (70 males, 33 females) and 108 matched HCs; and for the HNF-1 alpha, we employed 110 patients (80 males, 30 females) and 110 HCs. The blood biochemistry of the participants was essayed using commercial kits, and the methods of statistical analysis used were the Chi-square test, the Fisher exact test, and a multivariate analysis based on logistic regression, like the odds ratio (OD) and risk ratio (RR), with 95% confidence intervals (CIs). RESULTS: The MiR-27a rs895819 AG genotype was linked to increased T2D susceptibility, with OR = 2.01 and p-value = 0.011, and the miR-146 rs2910164 CG genotype and C allele were linked to an elevated risk of T2D, with OR = 2.75, p-value < 0.0016, OR = 1.77, and p-value = 0.004. The results also showed that the GT genotype and T allele of the HNF-1 alpha (rs1169288) G>T is linked to T2D, with OR = 2.18, p-value = 0.0061, and 1.77, p-value = 0.0059. CONCLUSIONS: The SNVs in miR-27a, miR-146, and HNF-1 alpha can be potential loci for T2D risk. The limitations of this study include the relatively small sample size and the fact that it was a cross-sectional study. To our knowledge, this is the first study to highlight the association between miR-27a, miR-146, and HNF-1 alpha SNVs and the risk of T2D in the Saudi population. Future large-scale case-control studies, as well as studies on the functions of the proteins and protein interaction studies for HNF-1 alpha, are required to verify our findings. Furthermore, these findings can be used for the identification and stratification of at-risk populations via genetic testing for T2D-prevention strategies.

Potential Impact of PI3K-AKT Signaling Pathway Genes, KLF-14, MDM4, miRNAs 27a, miRNA-196a Genetic Alterations in the Predisposition and Progression of Breast Cancer Patients.

Genome-wide association studies have reported link between SNPs and risk of breast cancer. This study investigated the association of the selected gene variants by predicting them as possible target genes. Molecular technique advances with the availability of whole-exome sequencing (WES), now offer opportunities for simultaneous investigations of many genes. The experimental protocol for PI3K, AKT-1, KLF-14, MDM4, miRNAs 27a, and miR-196a genotyping was done by ARMS-PCR and sanger sequencing. The novel and known gene variants were studied by Whole-exome sequencing using Illumina NovaSeq 6000 platform. This case control study reports significant association between BC patients, healthy controls with the polymorphic variants of PI3K C > T, AKT-1 G > A KLF 14 C > T, MDM4 A > G, miR-27a A > G, miR-196a-2 C > T genes (p < 0.05). MDM4 A > G genotypes were strongly associated with BC predisposition with OR 2.08 & 2.15, p < 0.05) in codominant and dominant models respectively. MDM4 A allele show the same effective (OR1.76, p < 0.05) whereas it remains protective in recessive model for BC risk. AKT1G > A genotypes were strongly associated with the BC susceptibility in all genetic models whereas PI3K C > T genotypes were associated with breast cancer predisposition in recessive model OR 6.96. Polymorphic variants of KLF-14 A > G, MDM4G > A, MiR-27aA >G, miR-196a-C > T were strongly associated with stage, tamoxifen treatment. Risk variants have been reported by whole exome sequencing in our BC patients. It was concluded that a strong association between the PI3K-AKT signaling pathway gene variants with the breast cancer susceptibility and progression. Similarly, KLF 14-AA, MDM4-GA, miR27a-GG and miR-196a-CT gene variants were associated with the higher risk probability of BC and were strongly correlated with staging of the BC patients. This study also reported Low, novel, and intermediate-genetic-risk variants of PI3K, AKT-1, MDM4G & KLF-14 by utilizing whole-exome sequencing. These variants should be further investigated in larger cohorts' studies.

Genome Investigation and Functional Annotation of Lactiplantibacillus plantarum YW11 Revealing Streptin and Ruminococcin-A as Potent Nutritive Bacteriocins against Gut Symbiotic Pathogens.

All nutrient-rich feed and food environments, as well as animal and human mucosae, include lactic acid bacteria known as Lactobacillus plantarum. This study reveals an advanced analysis to study the interaction of probiotics with the gastrointestinal environment, irritable bowel disease, and immune responses along with the analysis of the secondary metabolites' characteristics of Lp YW11. Whole genome sequencing of Lp YW11 revealed 2297 genes and 1078 functional categories of which 223 relate to carbohydrate metabolism, 21 against stress response, and the remaining 834 are involved in different cellular and metabolic pathways. Moreover, it was found that Lp YW11 consists of carbohydrate-active enzymes, which mainly contribute to 37 glycoside hydrolase and 28 glycosyltransferase enzyme coding genes. The probiotics obtained from the BACTIBASE database (streptin and Ruminococcin-A bacteriocins) were docked with virulent proteins (cdt, spvB, stxB, and ymt) of Salmonella, Shigella, Campylobacter, and Yersinia, respectively. These bacteria are the main pathogenic gut microbes that play a key role in causing various gastrointestinal diseases. The molecular docking, dynamics, and immune simulation analysis in this study predicted streptin and Ruminococcin-A as potent nutritive bacteriocins against gut symbiotic pathogens.

Myogenesis and Analysis of Antimicrobial Potential of Silver Nanoparticles (AgNPs) against Pathogenic Bacteria.

The widespread and indiscriminate use of broad-spectrum antibiotics leads to microbial resistance, which causes major problems in the treatment of infectious diseases. However, advances in nanotechnology have opened up new domains for the synthesis and use of nanoparticles against multidrug-resistant pathogens. The traditional approaches for nanoparticle synthesis are not only expensive, laborious, and hazardous but also have various limitations. Therefore, new biological approaches are being designed to synthesize economical and environmentally friendly nanoparticles with enhanced antimicrobial activity. The current study focuses on the isolation, identification, and screening of metallotolerant fungal strains for the production of silver nanoparticles, using antimicrobial activity analysis and the characterization of biologically synthesized silver nanoparticles by X-ray diffraction (XRD) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). In total, 11 fungal isolates were isolated and screened for the synthesis of AgNPs, while the Penicillium notatum (K1) strain was found to be the most potent, demonstrating biosynthetic ability. The biologically synthesized silver nanoparticles showed excellent antibacterial activity against the bacteria Escherichia coli (ATCC10536), Bacillus subtilis, Staphylococcus aureus (ATCC9144), Pseudomonas aeruginosa (ATCC10145), Enterococcus faecalis, and Listeria innocua (ATCC13932). Furthermore, three major diffraction peaks in the XRD characterization, located at the 2θ values of 28.4, 34.8, 38.2, 44, 64, and 77°, confirmed the presence of AgNPs, while elemental composition analysis via EDX and spherical surface topology with a scanning electron microscope indicated that its pure crystalline nature was entirely composed of silver. Thus, the current study indicates the enhanced antibacterial capability of mycologically synthesized AgNPs, which could be used to counter multidrug-resistant pathogens.

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.

Clinical and Serological Findings of COVID-19 Participants in the Region of Makkah, Saudi Arabia.

Makkah in Saudi Arabia hosts the largest annual religious event in the world. Despite the many strict rules enacted, including Hajj cancellation, city lockdowns, and social distancing, the region has the second highest number of new COVID-19 cases in Saudi Arabia. Public health interventions that identify, isolate, and manage new cases could slow the infection rate. While RT-PCR is the current gold standard in SARS-CoV-2 identification, it yields false positive and negative results, which mandates the use of complementary serological tests. Here, we report the utility of serological assays during the acute phase of individuals with moderate and severe clinical manifestations of SARS-CoV-2 (COVID19). Fifty participants with positive RT-PCR results for SARS-CoV-2 were enrolled in this study. Following RT-PCR diagnosis, serum samples from the same participants were analyzed using in-house ELISA (IgM, IgA, and IgG) and microneutralization test (MNT) for the presence of antibodies. Of the 50 individuals analyzed, 43 (86%) showed a neutralizing antibody titer of ≥20. Univariate analysis with neutralizing antibodies as a dependent variable and the degree of disease severity and underlying medical conditions as fixed factors revealed that patients with no previous history of non-communicable diseases and moderate clinical manifestation had the strongest neutralizing antibody response "Mean: 561.11". Participants with severe symptoms and other underlying disorders, including deceased individuals, demonstrated the lowest neutralizing antibody response. Anti-spike protein antibody responses, as measured by ELISA, showed a statistically significant correlation with neutralizing antibodies. This reinforces the speculation that serological assays complement molecular testing for diagnostics; however, patients' previous medical history (anamnesis) should be considered in interpreting serological results.