Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Kinetics, thermodynamics, and equilibrium of As(Ⅲ),Cd(Ⅱ), Cu(Ⅱ) and Pb(Ⅱ) adsorption using porous chitosan bead-supported MnFe_(2)O_(4) nanoparticles

A novel porous nanocomposite,cross-linked chitosan and polyethylene glycol(PEG) bead-supported MnFe_(2) O_(4) nanoparticles(CPM),was developed as an efficient adsorbent to remove metalloid(As(Ⅲ))and heavy metals(Cd(Ⅱ),Cu(Ⅱ),and Pb(Ⅱ)).The characteristics of CPM showed a porous structure,well dispersed MnFe_(2) O_(4),and several of hydroxyl and amino groups(-OH,-NH_(2)).Batch experiments demonstrated that the best adsorption property of As(Ⅲ),Cd(Ⅱ),Cu(Ⅱ),and Pb(Ⅱ) was achieved within 8 h with maximum adsorption capacities of 9.90,9.73,43.94,and 11.98 mg/g,respectively.Competitive and synergistic effects(particularly precipitation) were included in the co-adsorption mechanism of As(Ⅲ) and heavy metals.Thereinto,As(Ⅲ) was partly oxidized by MnFe_(2) O_(4) to As(V),and both were coordinated on MnFe_(2) O_(4) nanoparticles.Pb(Ⅱ) could also bind to MnFe_(2) O_(4) by ion exchange and electrostatic attraction.Furthermore,Cd(Ⅱ) and Cu(Ⅱ) tended to be coordinated on chitosan.Therefore,CPM can serve as a remediation material for water and soil co-contaminated with As(Ⅲ) and heavy metals.

Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms

BACKGROUND Chronic gastritis(CG) is an inflammatory disease of the gastric mucosa. Shenling-bai-zhu san(SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear.AIM To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG.METHODS We systematically searched 3 English(PubMed, Embase, Medline) and 4 Chinese databases(Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform,and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG.RESULTS Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that:(1) SLBZS was superior to conventional therapies [risk ratio(RR):1.29, 95% confidence interval(CI): 1.21 to 1.37, P < 0.00001];(2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval(95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity(RR: 1.20, 95%CI: 1.11 to 1.30,P < 0.00001);and(3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others.CONCLUSION SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.

Crosstalk between adipose-derived stem cells and chondrocytes:when growth factors matter

Adipose-derived stem cells（ASCs）and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity.Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes.However,the paracrine action of ASCs on chondrocytes needs to be further elucidated.In this study,we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1%fetal bovine serum to mimic the physiological microenvironment.In ASCs,we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2（BMP-2）,vascular endothelial growth factor B（VEGFB）,hypoxia inducible factor-1α（HIF-1α）,fibroblast growth factor-2（FGF-2）,and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture.In chondrocytes,VEGFA was significantly enhanced after co-culture.Unexpectedly,the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group.Meanwhile,among all the growth factors screened,we found that the BMP family members BMP-2,BMP-4,and BMP-5 were down-regulated and that VEGFB,HIF-1α,FGF-2,and PDGF were significantly decreased after co-culture.These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering.

Generation of knockout rabbits using transcription activator-like effector nucleases

Zinc-finger nucleases and transcription activator-like effector nucleases are novel gene-editing platformscontributing to redefine the boundaries of modern biological research. They are composed of a non-specificcleavage domain and a tailor made DNA-binding module, which enables a broad range of genetic modifications byinducing efficient DNA double-strand breaks at desired loci. Among other remarkable uses, these nucleases havebeen employed to produce gene knockouts in mid-size and large animals, such as rabbits and pigs, respectively.This approach is cost effective, relatively quick, and can produce invaluable models for human disease studies,biotechnology or agricultural purposes. Here we describe a protocol for the efficient generation of knockout rabbitsusing transcription activator-like effector nucleases, and a perspective of the field.