Diabetes mellitus is a complex metabolic disease involving multiple organ systems in the body.In recent years,its global incidence rate has increased year by year.In China,the blood glucose control of patients with diabetes mellitus who receive oral hypogly-cemic agents or insulin treatment remains poor.In the early disease stages,exercise is important to control blood glucose levels.Recently,many studies have found that the occurrence of type 2 diabetes mellitus was related to declining levels of irisin,an exercise-related muscle factor.Furthermore,studies have found that irisin improved insulin resistance,promoted the production of pancreatic isletβcells,and affected the body's glucose and lipid metabolism.In addition,its levels were also implicated in the occurrence of various complications,such as diabetic nephropathy and diabetes-related cardiovascular diseases.This article summarizes and analyzes the role of irisin in the occurrence and development of diabetes mellitus and further describes its impact and mechanism on various diabetic complications.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

As a metabolic disease,obesity increases the risk of many chronic metabolic diseases;in fact,it is an epidemic in the 21st cen-tury.Exercise is an important means of controlling and treating obesity.Irisin,a myocyte cytokine,was discovered and reported in 2012;it is regulated by exercise and involved in the browning of adipose tissue.A recent discovery is irisin's ability to improve obesity,which is embodied in its effect on glucose and lipid metabolism.Irisin can induce the browning of white fat;promote glucose homeostasis;resist the damage of fat cells caused by inflammation,oxidative stress,and other factors;inhibit insulin resistance;and improve glucose,lipid metabolism,and obesity.This review addresses the role of irisin in improving glucose levels,lipid metabolism,and obesity,as well its role in regulating exercise.Further,the prospect of future research is discussed.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Objective The objective of this study was to investigate the abnormal expression of Notch signaling pathway members in pancreatic cancer and its important effect on the development of pancreatic carcinoma. Methods Affymetrix gene expres-sion microarray was used to screen the differentially expressed members of Notch signal pathway in 10 cases of pancreatic carcinoma and its adjacent tissues,and verified by real-time quantitative PCR and Western blotting. The lentivirus expression vector carrying the siRNA fragment of Jagged 2(JAG2)gene was transfected into the pancreatic cancer primary cells to construct the JAG2 gene re-pression-expressing pancreatic cancer cell line. MTT,flow cytometry and Transwell assays were used to analyze cell proliferation, changes of cell cycle and invasive transfer capabilities. Results A total of 512 differentially expressed genes were detected by Affy-metrix gene expression microarray,including 419 up-regulated genes and 93 down-regulated genes. JAG2( up-regulated expres-sion 8. 20 times),NOTCH1(up-regulated expression 3. 74 times),HES1(up-regulated expression 3. 27 times),and NOTCH2(up-regulated expression 3. 16 times)were differentially expressed in Notch signaling pathway. The results of PCR and Western blotting were consistent with those of gene chip. The growth curves of JAG2 gene repressed pancreatic cancer cells and pancreatic cancer pri-mary cells were drawn by the standard OD490 value of d1-d5 by MTT assay. JAG2 gene repressor expression vector could signifi-cantly inhibit the proliferation of pancreatic cancer cells. The cell cycle analysis showed that the apoptosis and the arrested cell cycle at the S phase were significantly increased in pancreatic cancer cells with JAG2 gene repressor expression. The invasive ability was significantly reduced in JAG2 gene repressor expression pancreatic cancer cells(P<0. 05). Conclusion Some members of the Notch signaling pathway are significantly differentially expressed in pancreatic cancer tissues,and repression of this member can affect the growth,cell cycle,invasion and metastasis of pancreatic cancer cells.

Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.

ABSTRACT:Objective To explore role of U0126,the specific inhibitor of ERK signaling pathway,in early brain injury (EBI)and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group,SAH group,DMSO+SAH group,and U0126+SAH group,with 12 in each.We established SAH rat model by the puncture of internal carotid artery.The same amount of saline water,DMSO and U0126 solution of 0.5 mL per rat was injected respectively into the rats of different groups 30 min before modeling.The rats were killed at 24 h.To measure brain water content by Wet and dry method after 24 h,the morphological changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of ERK,Beclin-1 and LC3 were detected by using immunohistochemical method. Results Compared with that in sham group,brain water content increased obviously in SAH model group.The density of surviving neurons in SAH group was significantly lower than that in control group (P<0 .0 5 ).ERK signaling pathway was activated obviously,the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in control group (P<0.05).Compared with SAH model group,in U0126 group brain water content increased obviously.Compared with those in SAH group,the density of surviving neurons was significantly lower (P<0.05), ERK signaling pathway was suppressed,the expressions of Beclin-1 and LC3-Ⅱ were significantly lower (P<0.05). Conclusion The U0126,the ERK signaling pathway inhibitor,can inhibit neuron autophagy and increase EBR of SAH.