Molecular subtypes based on DNA methylation predict prognosis in patients with renal clear cell carcinoma

Background:Tumor heterogeneity is closely related to the occurrence,progression and recurrence of renal clear cell carcinoma(ccRCC),making early diagnosis and effective treatment difficult.DNA methylation is an important regulator of gene expression and can affect tumor heterogeneity.Methods:In this study,we investigated the prognostic value of subtypes based on DNA methylation status in 506 ccRCC samples with paired clinical data from the TCGA database.Differences in DNA methylation levels were associated with differences in T,N and M categories,age,stage and prognosis.Finally,the samples were divided into the training group and the testing group according to 450K and 27K.Univariate and multivariate Cox regression analysis was used to construct the prediction model in the training group,and the model was verified and evaluated in the testing group.Results:By univariate Cox regression analysis,21,122 methylation sites and 6,775 CpG sites were identified as potential DNA methylation biomarkers for overall survival of ccRCC patients(P<0.05).3,050 CpG sites independently associated with prognosis were identified with T,N,M,stage and age as covariables.Consensus cluster of 3,050 potential prognostic methylation sites was used to identify different DNA methylation subsets of ccRCC for prognostic purposes.We performed functional enrichment analysis on these 3,640 genes and identified 75 significantly enriched pathways(P<0.05).We then researched the expression of methylated genes in subgroups.Verifing with the training set,suggesting that DNA methylation levels generally reflect the expression of these genes.Conclusion:Based on TCGA database and a series of bioinformatics methods,We identified prognostic specific methylation sites and established prognostic prediction models for ccRCC patients.This model helps to identify novel biomarkers,precision drug targets and disease molecular subtypes in patients with ccRCC.Therefore,this model may be useful in predicting the prognosis,clinical diagnosis and management of patients with different epigenetic subtypes of ccRCC.

Mechanism of Chaihu Shugan Powder(柴胡疏肝散) for Treating Depression Based on Network Pharmacology

Objective:To analyze the effective components of Chinese medicine(CM)contained in Chaihu Shugan Powder(柴胡疏肝散,CSP)in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology.Methods:Absorption,distribution,metabolism,excretion,and toxicity calculation method was used to screen the active components of CSP.Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool(GoPuMed database)were used to predict and screen the active ingredients of CSP and anti-depressive targets.Through Genetic Association Database,Therapeutic Target Database,and PharmGkb database targets for depression were obtained.Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP,and to analyze gene function and metabolic pathways through Database for Annotation,Visualization and Integrated Discovery and the Omicshare database.Results:The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity,growth,transfer condition and gene expression of neuronal cell,and the raise of the expression of gap junction protein.The 15 targets passed 14 metabolic pathways,mainly involved in the regulation of neurotransmitters(5-hydroxytryptamine,dopamine and epinephrine),inflammatory mediator regulation of TRP channels,calcium signaling pathway,cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects.Conclusion:This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research,and lays a foundation for further target studies.

Effects of Tuina on serum creatine kinase and skeletal muscle mitochondria in delayed onset muscle soreness model rats

Objective To observe the effect of Tuina(Chinese therapeutic massage)on creatine kinase(CK),mitochondrial Ca^(2+)concentration,and ultrastructure of skeletal muscle in delayed onset muscle soreness(DOMS)model rats.Methods A total of 130 healthy male Sprague-Dawley rats were randomly divided into a blank group,an exercise control group,a pre-exercise Tuina group,and a post-exercise Tuina group.According to the time points for sample collection,the exercise control group was divided into a 0 h exercise control group,a 24 h exercise control group,a 48 h exercise control group,and a 72 h exercise control group;the pre-exercise Tuina group was further divided into a 0 h pre-exercise Tuina group,a 24 h pre-exercise Tuina group,a 48 h pre-exercise Tuina group,and a 72 h pre-exercise Tuina group;and the post-exercise Tuina group was divided into a 0 h post-exercise Tuina group,a 24 h post-exercise Tuina group,a 48 h post-exercise Tuina group,and a 72 h post-exercise Tuina group.Rats in all groups except for the blank group received DOMS modeling.Professionals performed Nie-Pinching manipulation and finger Nian-Twisting manipulation on the lower limbs of the rats.The samples were collected at 0 h,24 h,48 h,or 72 h after exhaustive exercise for each pre-exercise Tuina group.The samples were collected at 0 h,24 h,48 h,or 72 h after Tuina for each post-exercise Tuina group.The changes in serum CK,skeletal muscle mitochondrial Ca^(2+)concentration,and Ca^(2+)-adenosine triphosphatase(ATPase)were determined.The ultrastructure changes of skeletal muscles in each group were observed by a transmission electron microscope.Results The electron microscope showed that compared with the exercise control group,the skeletal muscle structures of the pre-exercise Tuina group and the post-exercise Tuina group were significantly improved,and the overall performance of skeletal muscle in the pre-exercise Tuina group was more similar to that of the blank group.The level of serum CK in the pre-exercise Tuina group and the post-exercise Tuina group was significantly lower than that in the exercise control group(P<0.01).The Ca^(2+)concentration of skeletal muscle in the 24 h,48 h,and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point(P<0.01).The Ca^(2+)-ATPase concentration of skeletal muscle in the 24 h and 72 h pre-exercise Tuina groups was lower than that in the post-exercise Tuina group at the same time point(P<0.05).Conclusion Tuina effectively prevents muscle damage caused by heavy exercise and long-term exercise,which may be related to the increase of skeletal muscle Ca^(2+)-ATPase activity and mitochondrial Ca^(2+)transport.

The Role of Intestinal Microbiota in Atopic Dermatitis

The early intestinal microbiota plays an important role in immune regulation,and the unbalanced composition may increase the occurrence of allergic diseases,including atopic dermatitis.This review summarizes the latest studies in the occurrence and development of intestinal microflora and its relationship with atopic dermatitis.These results are conducive to understand the differences in the composition of intestinal microbiota between patients with atopic dermatitis and healthy people,and provide a potential intervention for prevention or treatment of atopic dermatitis.