Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer (GC) is a common clinical condition of the digestive system. Reviewing 14 meta-analyses that evaluated the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and GC risk, we observed inconsistent results, and the credibility of the significant correlation between the statistical results was ignored. With the aim of further exploring the association between MTHFRC677T and CA1298C and the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publication bias was assessed by funnel plots. To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFRC677T polymorphism was significantly associated with GC risk, especially in Asians, while MTHFR CA1298C polymorphism was not associated with GC risk. However, in subgroup analysis by hospital-based controls, we found that MTHFR CA1298C might be a protective factor for GC. After credibility assessment, the statistical association between MTHFRC677T and GC susceptibility study was classified as "less credible positive result", while the result of MTHFR CA1298C was considered unreliable. In summary, this study strongly suggests that MTHFR, C677T and CA1298C polymorphisms are not significantly associated with the GC risk.

Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5′AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

Background. Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats. Methods. Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods. Results. Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT. Conclusions. Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.

Colorectal cancer pathogenesis is a multifactorial process, with genetic factors playing a significant role in cancer development. A review of published meta-analyses on MTHFR gene polymorphisms and colorectal cancer susceptibility showed inconsistent findings and failed to assess the reliability of statistically significant results. Case-control studies were manually searched in databases to investigate the association between MTHFR gene polymorphisms and colorectal cancer. The study assessed the strength of association for the five gene models by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The study results were also analyzed for the source of heterogeneity, sensitivity, publication bias, and false-positive report probability (FPRP) test. Additionally, extensive subgroup analyses were conducted to investigate the impact of confounding factors on the associations. The study suggests that MTHFR C677T gene polymorphism reduces the risk of colorectal cancer in Asian and mixed-race populations, while increasing the risk of Colorectal cancer in the Indian ethnic group. MTHFR A1298C may play a protective role in the development of colorectal cancer. These findings provide valuable insights for the early diagnosis and prevention of Colorectal cancer. However, further studies are required to confirm the association, which may offer additional information for the early diagnosis and prevention of Colorectal cancer.

Purpose Gastric cancer is one of the highly prevalent malignant tumours of the digestive tract in China and is highly lethal. Several studies have confirmed that Ferroptosis is closely related to the development of gastric cancer. disulfidptosis is a new type of cell death, which is a rapid death mode caused by disulfide stress induced by excessive cystine accumulation in the cell. Currently there are fewer studies on the discovery of disulfidptosis-related genes and their role in cancer development, and this study was used to explore the prognostic analysis of gastric cancer based on the disulfidptosis-related Ferroptosis genes. Methods The mRNA expression profiles of gastric cancer patients and corresponding clinical information were downloaded from the TCGA public database. Ferroptosis, disulfidptosis related gene ensembles were obtained from FerrDb database and published literature search. Differential expression analysis of genes was done on gastric cancer tissues and paracancerous tissues using the R package to screen out the disulfidptosis-related Ferroptosis-based genes with prognostic value. A prognostic model was constructed using LASSO Cox regression analysis, and the RiskScore of the corresponding genes was calculated, and the patients were classified into high-risk and low-risk groups according to the median value of the RiskScore. The predictive ability of the prognostic model for 1-year, 3-year, and 5-year survival was assessed by ROC curves. Multifactorial independent prognostic analysis was used to analyse the correlation between genes in the predictive model and clinicopathological features. The degree of immune infiltration of DEGs in gastric cancer tissues was analysed by Timer database. Results In the TCGA cohort, disulfidptosis-related Ferroptosis genes were differentially expressed between tumours and adjacent normal tissues. In this study, we constructed relevant prognostic models, including DUSP1, TSC22D3, AKR1C2, HNF4A, HELLS, SLC1A5, and BID, and divided the patients into two populations, high and low risk, according to the score of risk, and the overall survival rate of the high-risk group was significantly lower compared with that of the low-risk group (p < 0.001). In multifactorial Cox regression analysis, the risk score could be used as an independent prognostic factor (p < 0.05). The results of immune infiltration analysis showed that the expression level of each DEGs was significantly correlated with the level of immune cell infiltration in gastric cancer (p<0.05). Conclusion In this study, the disulfidptosis-related Ferroptosis gene prognostic model was constructed and identified as an independent prognostic factor, which provides a reference for the treatment and prognosis of gastric cancer patients.