Curcumin alleviates TGF-β1-induced fibrosis in NRK-49F cells via suppression of miR-21 expression,and regulation of the TGF-β1/smad3 signaling pathway

Objective:Overexpression of microRNA-21(miR-21)has been well-recognized during fibrosis in a wide range of tissue types through regulation of fibrogenesis via diverse pathways.Curcumin exhibits antifibrotic effects in various organs.We and others have previously demonstrated that curcumin has positive effects on the protection against fibrosis.However,the effect of curcumin on miR-21 expression has not been reported.Methods:In this study,transforming growth factor-b1(TGF-b1)-stimulated rat renal fibroblast cells(NRK-49F)were transfected with miR-21 inhibitors,then the expression of Smad3,a-smooth muscle actin(a-SMA),type I collagen(COL1A1),and type III collagen(COL3A1)was determined using quantitative real-time-PCR(qRT-PCR)and western blot analysis.The effect of curcumin on production of the extracellular matrix was evaluated using immunofluorescence,qRT-PCR,and western blot analysis.Results:TGF-b1 stimulation upregulated the expression of miR-21 and induced fibrogenesis in NRK-49F cells.Transfection with miR-21 inhibitors selectively decreased smad3 activity,and noticeably reduced the expression of a-SMA,COL1A1,and COL3A1.Curcumin treatment significantly inhibited the expressions of smad3,a-SMA,COL1A1,COL3A1,as well as miR-21 expression in NRK-49F cells in a dosedependent manner.Conclusion:Curcumin exerted its anti-fibrotic effects by targeting the TGF-b1/smad3 signaling pathway and suppressing miR-21 expression,thereby provides novel insight in the protective effects of curcumin against fibrosis in various organs.

Chiral carbon dots from glucose by room temperature alkaliassisted synthesis for electrocatalytic oxidation of tryptophan enantiomers

Chiral catalysis is one of the most direct and effective approach to obtain pure optical enantiomers.Chiral carbon dots(CDs)as carbon-based chiral catalysts show great potential in chiral catalysis.Herein,we report a facile one step base-catalyzed aldol condensation to fabricate the chiral CDs from glucose at ambient temperature and pressure.The formation of chiral CDs involves the processes of isomerization and aldol condensation.These chiral CDs have been demonstrated that they have selective capacity for electrocatalytic oxidization of tryptophan enantiomers.L type of CDs(LCDs)is more likely to catalyze L-tryptophan(Trp)than D-Trp with the selective factor(I_(L)/I_(D))of 1.60,whereas the D type of CDs(DCDs)tends to catalyze D-Trp(I_(L)/I_(D):0.63).Theoretical calculations combined with various contrast experiments(temperature and pH)demonstrate that the selectively electrocatalytic capacity of chiral CDs toward Trp isomers is due to the different hydrogen-bond interactions between chiral CDs and Trp.

Towards better analysis of machine learning models:A visual analytics perspective

Interactive model analysis,the process of understanding,diagnosing,and refining a machine learning model with the help of interactive visualization,is very important for users to efficiently solve real-world artificial intelligence and data mining problems.Dramatic advances in big data analytics have led to a wide variety of interactive model analysis tasks.In this paper,we present a comprehensive analysis and interpretation of this rapidly developing area.Specifically,we classify the relevant work into three categories:understanding,diagnosis,and refinement.Each category is exemplified by recent influential work.Possible future research opportunities are also explored and discussed.

Network Pharmacology-based Strategy for Predicting Active Ingredients and Potential Targets of Cuscutae semen and Lycii fructus in Spermatogenic Dysfunction

Background:Traditional Chinese Medicine(TCM)Cuscutae semen(SC,Tusizi from Cuscuta chinensis Lam.)and Lycii fructus(FL,Gouqi from Lycium barbarum L.),are also used as a herb pair(SC-FL)to treat various ailments,including spermatogenic dysfunction(SD),a disease responsible for low fertility in males.Objective:Herein,we will further determine the bioactive components,component targets and partial molecular mechanisms of the herb pair for the treatment of SD.Methods:We employed the traditional Chinese medicine systems pharmacology database in combination with Ultra high performance liquid chromatography(UHPLC)analysis to analyze the active ingredients of the SC-FL herbal pair and explore its possible targets and underlying mechanism in treatment of spermatogenic dysfunction(SD).Moreover,we used a Sprague-Dawley rat model,generated by using glucosides of Tripterygium wilfordii(GTW),to evaluate the effect of SC-FL and the underlying mechanism on SD and reliability of certain key targets and pathways obtained from the pharmacology analysis.Results:We identified 56 active ingredients in SC-LF affecting 41 overlapping gene signals that influenced SD treatment outcomes.262 Gene Ontology(GO)terms and 170 pathways were yielded under analyses of Gene Ontology,Kyoto Encyclopedia of Gene and Genome pathway from which we predicted that cell proliferation and apoptosis were the primary biological processes(BP)involved in the treatment of SD by SC-LF.The results showed that SC-FL treatment significantly improved the testicular organ coefficient along with sperm count and motility,while reduced testicular damage and testicular tissue cell apoptosis in SD model.Mechanistically,SC-FL significantly upregulated the expression levels of anti-apoptotic proteins AR and BCL2 and downregulated those of pro-apoptotic proteins BAD,BAX,cleaved caspase 3,and CASP3.Conclusion:Collectively,these results indicated that SC-FL elicited a protective effect by potentially regulating apoptosis,thus suggesting that it will represent an effective reagent for male infertility.