Oxidative stress is crucial to the biology of tumors. Oxidative stress’ potential predictive significance in colorectal cancer (CRC) has not been studied; nevertheless here, we developed a forecasting model based on oxidative stress to forecast the result of CRC survival and enhance clinical judgment. The training set was chosen from the transcriptomes of 177 CRC patients in GSE17536. For validation, 65 samples of colon cancer from GSE29621 were utilized. For the purpose of choosing prognostic genes, the expression of oxidative stress-related genes (OXEGs) was found. Prognostic risk models were built using multivariate Cox regression analysis, univariate Cox regression analysis, and LASSO regression analysis. The outcomes of the western blot and transcriptome sequencing tests were finally confirmed. ATF4, CARS2, CRP, GPX1, IL1B, MAPK8, MRPL44, MTFMT, NOS1, OSGIN2, SOD2, AARS2, and FOXO3 were among the 14 OXEGs used to build prognostic characteristics. Patients with CRC were categorized into low-risk and high-risk groups according on their median risk scores. Cox regression analysis using single and multiple variables revealed that OXEG-related signals were independent risk factors for CRC. Additionally, the validation outcomes from western blotting and transcriptome sequencing demonstrated that OXEGs were differently expressed. Using 14 OXEGs, our work creates a predictive signature that may be applied to the creation of new prognostic models and the identification of possible medication candidates for the treatment of CRC.

BackgroundIn recent years, the incidence rates of rheumatoid arthritis (RA) and heart disease (HD) have noticeably increased worldwide. Previous studies have found that patients with RA are more likely to develop HD, while the cause and effect have still remained elusive. In this study, Mendelian randomization (MR) analysis was used to indicate whether there was a potential association between RA and HD.MethodsData of RA, ischemic heart disease (IHD), myocardial infarction (MI), atrial fibrillation (AF), and arrhythmia were based on the genome-wide association study (GWAS) dataset. No disease group was intersected. Inverse-variance weighted (IVW) method was used to calculate MR estimates, and sensitivity analysis was performed.ResultsThe primary MR analysis showed that genetic susceptibility to RA was significantly associated with the risk of IHD and MI, rather than with AF and arrhythmia. Besides, there was no heterogeneity and horizontal pleiotropy between the primary and replicated analyses. There was a significant correlation between RA and the risk of IHD (odds ratio (OR), 1.0006; 95% confidence interval (CI), 1.000244–1.00104; P = 0.001552), meanwhile, there was a significant correlation between RA and the risk of MI (OR, 1.0458; 95% CI, 1.07061–1.05379; P = 0.001636). The results were similar to those of sensitivity analysis, and the sensitivity analysis also verified the conclusion. Furthermore, sensitivity and reverse MR analyses suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between RA and cardiovascular comorbidity.ConclusionRA was noted to be causally associated with IHD and MI, rather than with AF and arrhythmia. This MR study might provide a new genetic basis for the causal relationship between RA and the risk of CVD. The findings suggested that the control of RA activity might reduce the risk of cardiovascular disease.

BackgroundNumerous studies have demonstrated that rheumatoid arthritis (RA) is related to increased incidence of heart failure (HF), but the underlying association remains unclear. In this study, the potential association of RA and HF was clarified using Mendelian randomization analysis.MethodsGenetic tools for RA, HF, autoimmune disease (AD), and NT-proBNP were acquired from genome-wide studies without population overlap. The inverse variance weighting method was employed for MR analysis. Meanwhile, the results were verified in terms of reliability by using a series of analyses and assessments.ResultsAccording to MR analysis, its genetic susceptibility to RA may lead to increased risk of heart failure (OR=1.02226, 95%CI [1.005495-1.039304], P=0.009067), but RA was not associated with NT-proBNP. In addition, RA was a type of AD, and the genetic susceptibility of AD had a close relation to increased risk of heart failure (OR=1.045157, 95%CI [1.010249-1.081272], P=0.010825), while AD was not associated with NT-proBNP. In addition, the MR Steiger test revealed that RA was causal for HF and not the opposite (P = 0.000).ConclusionThe causal role of RA in HF was explored to recognize the underlying mechanisms of RA and facilitate comprehensive HF evaluation and treatment of RA.

Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in IBD. In this study, IBD expression profiles were screened from public Gene Expression Omnibus datasets. Functional enrichment analysis revealed that IBD-related specific functions were associated with immune pathways. Five MMPS-related disease markers, namely MMP-9, CD160, PTGDS, SLC26A8, and TLR5, were selected by machine learning and the correlation between each marker and immune cells was evaluated. We then induced colitis in C57 mice using sodium dextran sulfate and validated model construction through HE staining of the mouse colon. WB and immunofluorescence experiments confirmed that the expression levels of MMP-9, PTGDS, SLC26A8, and CD160 in colitis were significantly increased, whereas that of TLR5 were decreased. Flow cytometry analysis revealed that MMPs regulate intestinal inflammation and immunity mainly through CD8 in colitis. Our findings reveal that MMPs play a crucial role in the pathogenesis of IBD and are related to the infiltration of immune cells, suggesting that MMPs may promote the development of IBD by activating immune infiltration and the immune response. This study provides insights for further studies on the occurrence and development of IBD.