Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes

BACKGROUND A recently hypothesized cause of cell death called disulfidptosis has been linked to the expansion,emigration,and vascular rebuilding of cancer cells.Cancer can be treated by targeting the pathways that trigger cell death.AIM To discover the long non-coding RNA of the disulfidaptosis-related lncRNAs(DRLs),prognosis clinical survival,and treat patients with colorectal cancer with medications.METHODS Initially,we queried the Cancer Genome Atlas database to collect transcriptome,clinical,and genetic mutation data for colorectal cancer(CRC).Training and testing sets for CRC patient transcriptome data were generated randomly.Key long non-coding RNAs(lncRNAs)related to DRLs were then identified and evaluated using a least absolute shrinkage and selection operator procedure,as well as univariate and multivariate Cox regression models.A prognostic model was then created after risk scoring.Also,Immune infiltration analysis,immune checkpoint analysis,and medication susceptibility analysis were used to investigate the causes of the different prognoses between high and low risk groups.Finally,we validated the differential expression and biomarker potential of riskpredictive lncRNAs through induction using both NCM460 and HT-29 cell lines,as well as a disulfidptosis model.RESULTS In this work,eight significant lncRNAs linked to disulfidptosis were found.Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of differentially expressed genes between high-and low-risk groups from the prognostic model showed a close relationship with the immune response as well as significant enrichment in neutrophil extracellular trap formation and the IL-17 signaling pathway.Furthermore,significant immune cell variations between the high-risk and low-risk groups were seen,as well as a higher incidence of immunological escape risk in the high-risk group.Finally,Epirubicin,bortezomib,teniposide,and BMS-754807 were shown to have the lowest sensitivity among the four immunotherapy drugs.CONCLUSION Our findings emphasizes the role of disulfidptosis in regulating tumor development,therapeutic response,and patient survival in CRC patients.For the clinical treatment of CRC,these important LncRNAs could serve as viable therapeutic targets.

Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases

Severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)infection can lead to a cytokine storm,unleashed in part by pyroptosis of virus-infected macrophages and monocytes.Interleukin-6(IL-6)has emerged as a key participant in this ominous complication of coronavirus disease 2019(COVID-19).IL-6 antagonists have improved outcomes in patients with COVID-19 in some,but not all,studies.IL-6 signaling involves at least 3 distinct pathways,including classic-signaling,trans-signaling,and trans-presentation depending on the localization of IL-6 receptor and its binding partner glycoprotein gp130.IL-6 has become a therapeutic target in COVID-19,cardiovascular diseases,and other inflammatory conditions.However,the efficacy of inhibition of IL-6 signaling in metabolic diseases,such as obesity and diabetes,may depend in part on cell type-dependent actions of IL-6 in controlling lipid metabolism,glucose uptake,and insulin sensitivity owing to complexities that remain to be elucidated.The present review sought to summarize and discuss the current understanding of how and whether targeting IL-6 signaling ameliorates outcomes following SARS-CoV-2 infection and associated clinical complications,focusing predominantly on metabolic and cardiovascular diseases.

Interleukin-18, matrix metalloproteinase-22 and -29 are independent risk factors of human coronary heart disease

Background： Coronary heart disease （CHD） is characterized by arterial wall inflammation and matrixdegradation. Matrix metalloproteinase （MMP）-22 and -29 and pro-inflammatory cytokine interleukin-18 （IL18） arepresent in human hearts. IL18 may regulate MMP-22 and -29 expression, which may correlate with CHD progression.Methods and results： Immunoblot analysis showed that ILl8 induced MMP-22 expression in human aortic smoothmuscle cells. The Mann Whitney test from a prospective study of 194 CHD patients and 68 non-CHD controlsdemonstrated higher plasma levels of IL18, MMP-22 and-29 in CHD patients than in the controls. A logistic regressiontest suggested that plasma IL18 （odds ratio （OR）=1.131, P=0.007）, MMP-22 （OR=1.213, P=0.040）, and MMP-29（OR=1.198, P=0.033） were independent risk factors of CHD. Pearson＇s correlation test showed that IL18 （coefficient（r）=0.214, P=0.045; r=0.246, P=0.031） and MMP-22 （t=0.273, P=0.006; r=0.286, P=0.012） were associated with theGensini score before and after adjusting for potential confounding factors. The multivariate Pearson＇s correlation testshowed that plasma MMP-22 levels correlated positively with high-sensitive-C-reactive protein （hs-CRP） （r=0.167,P=0.023）, and MMP-29 levels correlated negatively with triglyceride （t=-0.169, ,P=-0.018）. Spearman＇s correlation testindicated that plasma IL18 levels associated positively with plasma MMP-22 （t=0.845, P〈0.001） and MMP-29 （r=0.548P〈0.001）. Conclusions： Our observations suggest that IL18, MMP-22 and -29 serve as biomarkers and independentrisk factors of CHD. Increased systemic IL18 in CHD patients may contribute to elevated plasma MMP-22 and -29levels in these patients.

COVID-19,the Pandemic of the Century and Its Impact on Cardiovascular Diseases

COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection likely ranks among the deadliest diseases in human history.As with other coronaviruses,SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2(ACE2),a receptor for SARS-CoV-2.COVID-19 has upended lives worldwide.Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications,while patients have avoided hospital visits because of limited resources and the fear of infection,thereby increasing out-hospital mortality due to delayed diagnosis and treatment.Clinical observations show that sex,age,and race all influence the risk for SARS-CoV-2 infection,as do hypertension,obesity,and pre-existing cardiovascular conditions.Many hospitalized COVID-19 patients suffer cardiac injury,acute coronary syndromes,or cardiac arrhythmia.SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis,endothelial cell damage and dysfunction,oxidative stress and reactive oxygen species production,vasoconstriction,fibrotic and thrombotic protein expression,vascular permeability and microvascular dysfunction,heart inflammatory cell accumulation and activation,and a cytokine storm.Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors,angiotensin receptor blockers,steroids,aspirin,statins,and PCSK9 inhibitors.This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.