Jiangtangjing ameliorates type 2 diabetes through effects on the gut microbiota and cAMP/PKA pathway

Background:During the clinical use of Jiangtangjing granules,we have found that they improve glucose metabolism and relieve symptoms in patients with type 2 diabetes mellitus.We aimed to further investigate the hypoglycemic effects of Jiangtangjing granules and the mechanisms involved.Methods:Type 2 diabetes mellitus was induced in rats by high-fat diet feeding and streptozotocin injection.The rats were then orally administered Linagliptin(3 mg/kg)or Jiangtangjing granules(13 g crude preparation/kg)for 4 weeks.The therapeutic effects of Jiangtangjing granules on glucose metabolism were then investigated.The serum glucagon-like peptide-1,insulin and glycosylated hemoglobin concentrations were measured using enzyme linked immunosorbent assay.Immunohistochemistry and quantificational real-time polymerase chain reaction were performed to quantify glucagon-like peptide-1 protein expression and cAMP,protein kinase A,and Epac1 mRNA expression,respectively.In addition,amplicon sequencing of bacterial 16s rDNA genes in rat feces was also performed to analyze the richness and diversity of the intestinal microbiota and to determine the relative abundances of the dominant bacterial phyla in the intestinal contents of the rats.Results:Jiangtangjing reduced fasting blood glucose concentration(P<0.05)and blood glucose concentrations during oral glucose tolerance testing(P<0.01),increased serum glucagon-like peptide-1 concentration after glucose administration(P<0.05)and improved glucose tolerance(P<0.05).It also increased glucagon-like peptide-1 protein expression(P<0.05)and the mRNA expression of cAMP(P<0.05),PKA(P<0.05),and Epac1(P<0.05)in the jejunum.Jiangtangjing also affected the composition of the intestinal microbiota in rats with type 2 diabetes mellitus.Specifically,it increased the relative abundance of Bacteroides and reduced that of Actinobacteria.Conclusion:Jiangtangjing granules have anti-diabetic effects,increasing circulating insulin concentration and glucose tolerance.These effects may be mediated by increases in glucagon-like peptide-1 secretion via upregulation of the cAMP/PKA signaling pathway in the jejunum and alterations in the composition of the intestinal microbiota.

Integration of multi-omics in investigations on the mechanisms of action of Chinese herbal medicine interventions in metabolic diseases

The rapid development of bioinformatics has provided novel approaches and methods for exploring the mechanisms of disease treatment via Chinese herbal medicines.Compound Chinese herbal medicines formulas have complex compositions and are characterized by their multiple constituents and diverse array of biological targets.Therefore,the mechanisms of action of most compound Chinese herbal medicines formulas cannot be adequately explained using a single pathway.Omics technologies describe high-throughput-based analytical and detection techniques,which include transcriptomics,proteomics,and metabolomics and provide multilayer parameter information that can be integrated to characterize the overall relationships involved in the therapeutic effects of Chinese herbal medicines formulas.Through their combination with network biology and drug effect networks,omics technologies also enable investigations into the mechanisms of disease treatment in traditional Chinese medicine.The integration of multiple omics technologies is in line with the concept of holism in traditional Chinese medicine and provides an approach for combining modern science and technology with traditional Chinese medicine theories.In recent years,omics technologies have been widely used to elucidate the mechanisms of action of Chinese herbal medicines.The latest studies employing multi-omics integration for investigating the mechanisms of action of Chinese herbal medicines interventions in metabolic diseases have devoted greater attention to in-depth explorations of disease pathogenesis.This paper provides a review of the following multi-omics technologies,which are used in research on the treatment of common metabolic diseases(e.g.,type-2 diabetes mellitus,nonalcoholic fatty liver disease):network pharmacology combined with metabolomics,16S rRNA sequencing combined with transcriptomics,16S rRNA sequencing combined with metabolomics,and 16S rRNA sequencing combined with network pharmacology and metabolomics.

Thin-walled and large-sized magnesium alloy die castings for passenger car cockpit:Application,materials,and manufacture

In order to effectively reduce energy consumption and increase range mile,new energy vehicles represented by Tesla have greatly aroused the application of integrated magnesium(Mg)alloy die casting technology in automobiles.Previously,the application of Mg alloys in automobiles,especially in automotive cockpit components,is quite extensive,while it has almost disappeared for a period of time due to its relatively high cost,causing a certain degree of information loss in the application technology of Mg alloy parts in automobiles.The rapid development of automotive technology has led to a higher requirement for the automotive components compared with those traditional one.Therefore,whatever the components themselves,or the Mg alloy materials and die casting process have to face an increasing challenge,needing to be upgraded.In addition,owing to its high integration characteristics,the application of Mg alloy die casting technology in large-sized and thin-walled automotive parts has inherent advantages and needs to be expanded urgently.Indeed,it necessitates exploring advance Mg alloys and new product structures and optimizing die casting processes.This article summarizes and analyzes the development status of thin-walled and large-sized die casting Mg alloy parts in passenger car cockpit and corresponding material selection methods,die casting processes as well as mold design techniques.Furthermore,this work will aid researchers in establishing a comprehensive understanding of the manufacture of thin-walled and large-sized die casting Mg alloy parts in automobile cockpit.It will also assist them in developing new Mg alloys with improved comprehensive performance and new processes to meet the high requirements for die casting automotive components.

Non-coding RNAs in cancers with chromosomal rearrangements:the signatures,causes,functions and implications

Chromosomal translocation leads to the juxtaposition of two otherwise separate DNA loci,which could result in gene fusion.These rearrangements at the DNA level are catastrophic events and often have causal roles in tumorigenesis.The oncogenic DNA messages are transferred to RNA molecules,which are in most cases translated into cancerous fusion proteins.Gene expression programs and signaling pathways are altered in these cytogenetically abnormal contexts.Notably,non-toding RNAs have attracted increasing attention and are believed to be tightly associated with chromosome-rearranged cancers.These RNAs not only function as modulators in downstream pathways but also directly affect chromosomal translocation or the associated products.This review summarizes recent research advances on the relationship between non-coding RNAs and chromosomal translocations and on diverse functions of non-coding RNAs in cancers with chromosomal rearrangements.

Small nucleolar RNA is potential as a novel player in leukemogenesis and clinical application

Lack of clarity of the mechanisms that underlie leukemogenesis obstructs the diagnosis,prognosis,and treatment of leukemia.Research has found that small nuclear RNA(snoRNA)plays an essential role in leukemia.These small non-coding RNAs are involved in ribosome biogenesis,including the 2'-O-methylation and pseudouridylation of precursor ribosomal RNA(pre-rRNA),and pre-rRNA splicing.Recently,many snoRNAs were found to be orphans that have no predictable RNA modification targets,but these RNAs have always been found to be located in different subcellular organelles,and they play diverse roles.Using high-throughput technology,snoRNA expression profiles have been revealed in leukemia,and some of the deregulated snoRNAs may regulate the cell cycle,differentiation,proliferation,and apoptosis in leukemic cells and confer drug resistance during leukemia treatment.In this review,we discuss the expression profiles and functions of snoRNAs,particularly orphan snoRNAs,in leukemia.It is possible that the dysregulated snoRNAs are promising diagnosis and prognosis markers for leukemia,which may serve as potential therapeutic targets in leukemia treatment.