Effect of UBR5 on the tumor microenvironment and its related mechanisms in cancer

Objective UBR5,recently identified as a potential target for cancer therapeutics,is overexpressed in multiple malignant tumors.In addition,it is closely associated with the growth,prognosis,metastasis,and treatment response of multiple types of cancer.Although emerging evidence supports the relationship between UBR5 and cancer,there are limited cancer analyses available.Methods In this study,online databases(TIMER2,GEPIA2,UALCAN,c-BioPortal,STRING)were employed to comprehensively explore expression levels and prognostic values of the UBR5 gene in cancer,using bioinformatic methods.Results We found that various characteristics of the UBR5 gene such as gene expression,survival value,genetic mutation,protein phosphorylation,immune infiltration,and pathway activities in the normal tissue were remarkably different from those in the primary tumor.Furthermore,“protein processing in spliceosome”and“ubiquitin mediated proteolysis”have provided evidence for their potential involvement in the development of cancer.Conclusion Our findings may provide insights for the selection of novel immunotherapeutic targets and prognostic biomarkers for cancer.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models:A Cross-sectional Study in Rural Guangxi

Objective This study aimed to investigate the potential relationship between urinary metals copper(Cu),arsenic(As),strontium(Sr),barium(Ba),iron(Fe),lead(Pb)and manganese(Mn)and grip strength.Methods We used linear regression models,quantile g-computation and Bayesian kernel machine regression(BKMR)to assess the relationship between metals and grip strength.Results In the multimetal linear regression,Cu(β=−2.119),As(β=−1.318),Sr(β=−2.480),Ba(β=0.781),Fe(β=1.130)and Mn(β=−0.404)were significantly correlated with grip strength(P<0.05).The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was−1.007(95%confidence interval:−1.362,−0.652;P<0.001)when each quartile of the mixture of the seven metals was increased.Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength,with Cu,As and Sr being negatively associated with grip strength levels.In the total population,potential interactions were observed between As and Mn and between Cu and Mn(P_(interactions) of 0.003 and 0.018,respectively).Conclusion In summary,this study suggests that combined exposure to metal mixtures is negatively associated with grip strength.Cu,Sr and As were negatively correlated with grip strength levels,and there were potential interactions between As and Mn and between Cu and Mn.

Vitamin C exerts anti-cadmium induced fracture functions/targets:bioinformatic and biostructural findings

Background:Epidemiological data indicate an association between cadmium exposure and risk of bone fracture;however,clinical treatment of cadmium-induced fracture is limited.Although vitamin C(VC)reportedly reduces cadmium-induced fracture,its pharmacological mechanism remains unexplored.Methods:Thus,we used a network pharmacology approach and molecular docking analysis to identify core targets,functional processes,and biological pathways involved in the anti-fracture action of VC.Results:Bioinformatics identified 17 intersection targets of VC and cadmium-induced fracture,Nine core targets were characterized,including tumor protein p53,epidermal growth factor receptor,proto-oncogene c,mitogen-activated protein kinase-1(MAPK1),MAPK3,signal transducer and activator of transcription-3,MAPK14,prostaglandin-endoperoxide synthase 2,and estrogen receptor alpha.Interestingly,findings of molecular docking analysis indicated that VC exerted effective binding capacity in cadmium-induced fracture.Furthermore,biological processes,cell components,molecular functions,and pharmacological pathways involved in the action of VC against cadmium-induced fracture were identified and visualized.Conclusions:Based on these findings,we conclude that VC exhibits its anti-cadmium-induced fracture effects by promoting osteoblastic regeneration and proliferation,and inhibiting inflammatory stress.The core targets may serve as biomarkers for diagnosing cadmium-induced fractures.

Anti-hepatic carcinoma mechanisms of calycosin through targeting ferroptosis

Background Ferroptosis,a pathologic state induced by lipid-driven oxidative stress,is associated with the development of human cancers.Calycosin,a natural compound with antioxidant and anti-inflammatory activities,has promising antitumor effects.However,the ferroptosis-related mechanism of calycosin in the treatment of hepatic carcinoma has not been reported.Methods This study applied network pharmacology and bioinformatic approaches(including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis)to investigate the pharmacologic targets and mechanism of action of calycosin in the treatment of hepatic carcinoma through targeting ferroptosis.By searching online databases including The Cancer Genome Atlas,FerrDb,GeneCards,SwissTargetPrediction,SuperPred,BindingDB,TargetNet,BATMAN-TCM,and Drugbank,we identified 13 ferroptosis-related putative target genes of calycosin against hepatic carcinoma including IL-6,PTGS2,SRC,HRAS,NQO1,NOX4,PGK1,G6PD,GPI,MIF,NOS2,ALDOA,and SQSTM1.Results Molecular docking analysis revealed that calycosin potentially binded directly with the target proteins IL-6,PTGS2,and SRC.Functional enrichment analysis of these proteins indicated that they were involved in gluconeogenesis and apoptosis through regulation of ERK1,ERK2,and MAPK activities(P<0.05).Conclusion Calycosin exerts antitumor effects in hepatic carcinoma by targeting ferroptosis through regulation of IL-6,PTGS2,and SRC.