Association of HLA gene polymorphisms with Helicobacter pylori related gastric cancer-a systematic review.

The appropriate host cell immune responses for the progression of several diseases, including gastric or stomach cancer (GC), are significantly influenced by HLA polymorphisms. Our objective was to systematically review the evidence linking HLA polymorphisms with the risk of Helicobacter. pylori related GC. We conducted a comprehensive literature search to identify studies published between 2000 and April 2023 on the association of HLA polymorphisms with H. pylori related GC using databases such as Medline through PubMed, Embase, Web of Science (core collection), The Cochrane Library, and Scopus. Two authors independently screened articles, extracted data, and assessed the risk of bias using the Risk of Bias Assessment tool for Non-randomized Studies. From 7872 retrieved studies, 19 met inclusion criteria, encompassing 1656 cases and 16,787 controls across four World Health Organization regions, with Japan contributing the most studies. We explored HLA-A/B/C, HLA-DRB1/DQA1/DQB1, HLA-G, and MICA alleles. Of 29 significant HLA polymorphisms identified, 18 showed a positive association with GC, whereas 11 were negatively associated. HLA-DQB1*06 allele was most frequently associated to susceptibility, as reported in four studies, followed by HLA-DRB1*04 and HLA-DQA1*01, each reported in two studies. Conversely, HLA-G*01, HLA-DQA1*01, HLA-DQA1*05, and HLA-DQB1*03 were identified as protective in two studies each. Additionally, five genotypes and six haplotypes were reported as positive, whereas three genotypes and two haplotypes were negative factors for the disease incidence or mortality. Despite heterogeneity in the study population and types of HLA polymorphisms examined, our analysis indicates certain polymorphisms are associated with H. pylori related GC progression and mortality in specific populations.

Beta, Delta, and Omicron, Deadliest Among SARS-CoV-2 Variants: A Computational Repurposing Approach.

SARS-CoV-2 has been highly susceptible to mutations since its emergence in Wuhan, China, and its subsequent propagation due to containing an RNA as its genome. The emergence of variants with improved transmissibility still poses a grave threat to global health. The spike protein mutation is mainly responsible for higher transmissibility and risk severity. This study retrieved SARS-CoV-2 variants structural and nonstructural proteins (NSPs) sequences from several geographic locations, including Africa, Asia, Europe, Oceania, and North and South America. First, multiple sequence alignments with BioEdit and protein homology modeling were performed using the SWISS Model. Then the structure visualization and structural analysis were performed by superimposing against the Wuhan sequence by Pymol to retrieve the RMSD values. Sequence alignment revealed familiar, uncommon regional among variants and, interestingly, a few unique mutations in Beta, Delta, and Omicron. Structural analysis of such unique mutations revealed that they caused structural deviations in Beta, Delta, and Omicron spike proteins. In addition, these variants were more severe in terms of hospitalization, sickness, and higher mortality, which have a substantial relationship with the structural deviations because of those unique mutations. Such evidence provides insight into the SARS-CoV-2 spike protein vulnerability toward mutation and their structural and functional deviations, particularly in Beta, Delta, and Omicron, which might be the cause of their broader coverage. This knowledge can help us with regional vaccine strain selection, virus pathogenicity testing, diagnosis, and treatment with more specific vaccines.