Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been establishe...Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.展开更多
Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed S...Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People’s Hospital from January 11 th to February 10 th,2020 were included.The data were obtained from electronic medical records.The epidemiological data,clinical characteristics,length of hospital stays,and outcomes of pediatric and adult patients were compared.Results Compared with adult patients,pediatric patients had a shorter time of symptom onset to hospitalization than adults[median time,1(IQR,1.0-1.0)d vs.3(IQR,2.0-6.0)d,P<0.001],milder or fewer symptoms,less severe chest CT findings.The clinical severity classification of children was less severe than adults.Up to 15 th March,the end of the follow-up,33(100%)children and 292(97.3%)adult patients had been discharged from hospital.Only 2(0.7%)adult patients died,with an overall case mortality of 0.6%.The median length of hospital stay of pediatric patients was shorter than that of adult patients[19(95%CI:16.6-21.4)d vs.21(95%CI:19.9-22.1)d,P=0.024].Conclusion Pediatric patients with COVID-19 had milder or less clinical symptoms,less evident pulmonary imaging changes,better prognosis,and shorter length of hospital stay.展开更多
The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospit...The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected.Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients.The least absolute shrinkage and selection operator(LASSO)logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients.The concordance index(C-index)was used to assess the discrimination of the model,and internal validation was performed through bootstrap resampling.A novel predictive nomogram was constructed by incorporating these features.Of the 104 patients included in the study(median age 55 years),75(72.1%)had improved short-term outcomes,while 29(27.9%)showed no signs of improvement.There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes.After a multi-step screening process,prognostic factors were selected and incorporated into the nomogram construction,including immunoglobulin A(IgA),C-reactive protein(CRP),creatine kinase(CK),acute physiology and chronic health evaluation II(APACHE II),and interaction between CK and APACHE II.The C-index of our model was 0.962(95%confidence interval(CI),0.931-0.993)and still reached a high value of 0.948 through bootstrapping validation.A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve.The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient,which may facilitate personalized counselling and treatment.展开更多
Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the b...Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.展开更多
Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinician...Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.展开更多
To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-ter...To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.展开更多
Hepatitis B virus(HBV)establishes chronic infection through strategic manipulation of host metabolic networks,driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma....Hepatitis B virus(HBV)establishes chronic infection through strategic manipulation of host metabolic networks,driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma.Mechanistically,HBV reprograms core metabolic pathways,including glycolysis,tricarboxylic acid(TCA)cycle,oxidative phosphorylation,and lipid homeostasis,to fuel its replication machinery and evade immune surveillance.This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring,with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.展开更多
Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has bee...Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has been given to the crosstalk among them.In this study,we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment.Methods Three ALF-related datasets(GSE14668,GSE62029,and GSE74000)were downloaded from the Gene Expression Omnibus(GEO)database to identify differentially expressed genes(DEGs).Hub genes were identified through intersecting DEGs,genes obtained from weighted gene co-expression network analysis(WGCNA),and genes related to PANoptosis.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein–protein interaction(PPI)analyses and gene set enrichment analysis(GSEA)were performed to determine functional roles.Verification was performed using an ALF mouse model.Results Our results showed that expression of seven hub genes(B-cell lymphoma-2-modifying factor(BMF),B-cell lymphoma-2-interacting protein 3-like(BNIP3L),Caspase-1(CASP1),receptor-interacting protein kinase 3(RIPK3),uveal autoantigen with coiled-coil domains and ankyrin repeats protein(UACA),uncoordinated-5 homolog B receptor(UNC5B),and Z-DNA-binding protein 1(ZBP1))was up-regulated in liver samples of patients.However,in the ALF mouse model,the expression of BNIP3L,RIPK3,phosphorylated RIPK3(P-RIPK3),UACA,and cleaved caspase-1 was up-regulated,while the expression of CASP1 and UNC5B was down-regulated.The expression of ZBP1 and BMF increased only during the development of ALF,and there was no significant change in the end stage.Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers.Western blot results showed that pyroptosis,apoptosis,and necroptosis were always involved in lipopolysaccharide(LPS)/D-galactosamine(D-gal)-induced ALF mice.The ALF cell model showed that bone marrow-derived macrophages(BMDMs)form PANoptosomes after LPS stimulation.Conclusions Our results suggest that PANoptosis of macrophages promotes the development of ALF.The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.展开更多
Nuclear factor erythroid 2-related factor 2(Nrf2)is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions.Mitochondria are vital or...Nuclear factor erythroid 2-related factor 2(Nrf2)is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions.Mitochondria are vital organelles that function in diverse metabolic processes in the body,including redox reactions,lipid metabolism,and cell death.Mitophagy,a specific form of autophagy for damaged mitochondria,plays a critical role in the pathophysiology of liver diseases.In this review,we explain in detail the roles of the Nrf2 signaling pathway and mitophagy,and the relationship between them,in various hepatic diseases(nonalcoholic fatty liver disease,viral hepatitis,alcoholic liver disease,drug-induced liver injury,autoimmune hepatitis,hepatic ischemia-reperfusion injury,and liver cancer).We also offer some potential insights and treatments relevant to clinical applications.展开更多
Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV ...Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.展开更多
Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)...Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.展开更多
Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.T...Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.展开更多
The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and...The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.展开更多
In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degree...In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.展开更多
γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity.Based on the composition of T cell receptor and the cytokines produced,γδT cells can be divided into diverse subsets that may be ...γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity.Based on the composition of T cell receptor and the cytokines produced,γδT cells can be divided into diverse subsets that may be present at different locations,including the liver,epithelial layer of the gut,the dermis and so on.Many of these cells perform specific functions in liver diseases,such as viral hepatitis,autoimmune liver diseases,non-alcoholic fatty liver disease,liver cirrhosis and liver cancers.In this review,we discuss the distribution,subsets,functions ofγδT cells and the relationship between the microbiota andγδT cells in common hepatic diseases.AsγδT cells have been used to cure hematological and solid tumors,we are interested inγδT cell-based immunotherapies to treat liver diseases.展开更多
Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology.Also,microbiome-based therapies have been used to improve health status and treat diseases.In addition,agi...Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology.Also,microbiome-based therapies have been used to improve health status and treat diseases.In addition,aging and neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease,have become topics of intense interest in biomedical research.Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease.But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear.As technology advances,new techniques for studying the microbiome will be developed and refined,and the relationship between diseases and gut microbiota will be revealed.This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases,highlighting assay techniques for the gut microbiome,and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.展开更多
BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall ...BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.展开更多
Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases,injury repair,degenerative diseases,and tumors.Exosomes are small vesicles rich in a variety of nucleic acids[including mes...Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases,injury repair,degenerative diseases,and tumors.Exosomes are small vesicles rich in a variety of nucleic acids[including messenger RNA,Long non-coding RNA,microRNA(miRNA),and circular RNA],proteins,and lipids.Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells.Like exosomes,miRNAs were neglected before their role in various activities of organisms was discovered.Several studies have confirmed that miRNAs play a vital role within exosomes.This review focuses on the specific role of miRNAs in MSC-derived exosomes(MSC-exosomes)and the methods commonly used by researchers to study miRNAs in exosomes.Taken together,miRNAs from MSC-exosomes display immense potential and practical value,both in basic medicine and future clinical applications,in treating several diseases.展开更多
Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B ...Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B and E(colistin)constitute the last-line therapies for treating MDR Gram-negative bacteria.Polymyxin is a cationic antibacterial peptide that can destroy the outer membrane of Gram-negative bacteria.With the increasing clinical application of polymyxin,however,there have been many reports of the occurrence of polymyxin-resistant Gram-negative bacteria.This resistance is mainly mediated by the modification or complete loss of lipopolysaccharide(LPS).LPS is also a virulence factor of Gram-negative bacteria,and alterations of LPS may correlate with virulence.Although it is generally believed that the biological costs associated with drug resistance may enable benign susceptible bacteria to overcome resistant bacteria when antibiotic pressure is reduced,some studies have shown that polymyxin-resistant bacteria are associated with higher virulence and greater fitness compared with their susceptible counterparts.To predict the development of polymyxin resis-tance and evaluate interventions for its mitigation,it is important to understand the relative biological cost of polymyxin resistance compared with susceptibility.The impact of polymyxin resistance mecha-nisms on the virulence and fitness of these three Gram-negative bacteria are summarized in this review.展开更多
基金This study was supported by grants from the National Key Research and Development Program of China(2018YFC2000500)the National Natural Science Foundation of China(81790631 and 81330011).
文摘Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.
基金supported by the National Clinical Research Center for Infectious DiseasesFunds for the Construction of Key Medical Disciplines in Shenzhen and the Sanming Project of Medicine in Shenzhen[SZSM201612014]。
文摘Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People’s Hospital from January 11 th to February 10 th,2020 were included.The data were obtained from electronic medical records.The epidemiological data,clinical characteristics,length of hospital stays,and outcomes of pediatric and adult patients were compared.Results Compared with adult patients,pediatric patients had a shorter time of symptom onset to hospitalization than adults[median time,1(IQR,1.0-1.0)d vs.3(IQR,2.0-6.0)d,P<0.001],milder or fewer symptoms,less severe chest CT findings.The clinical severity classification of children was less severe than adults.Up to 15 th March,the end of the follow-up,33(100%)children and 292(97.3%)adult patients had been discharged from hospital.Only 2(0.7%)adult patients died,with an overall case mortality of 0.6%.The median length of hospital stay of pediatric patients was shorter than that of adult patients[19(95%CI:16.6-21.4)d vs.21(95%CI:19.9-22.1)d,P=0.024].Conclusion Pediatric patients with COVID-19 had milder or less clinical symptoms,less evident pulmonary imaging changes,better prognosis,and shorter length of hospital stay.
基金supported by the research on the prevention and clinical treatment in patients with COVID-19(2020C03123)a funding of the Zhejiang Provincial Department of Science and Technology+1 种基金the National Natural Science Foundation of China(81790631)the National Key Research and Development Program of China(2018YFC2000500).
文摘The aim of this research was to develop a quantitative method for clinicians to predict the probability of improved prognosis in patients with coronavirus disease 2019(COVID-19).Data on 104 patients admitted to hospital with laboratory-confirmed COVID-19 infection from 10 January 2020 to 26 February 2020 were collected.Clinical information and laboratory findings were collected and compared between the outcomes of improved patients and non-improved patients.The least absolute shrinkage and selection operator(LASSO)logistics regression model and two-way stepwise strategy in the multivariate logistics regression model were used to select prognostic factors for predicting clinical outcomes in COVID-19 patients.The concordance index(C-index)was used to assess the discrimination of the model,and internal validation was performed through bootstrap resampling.A novel predictive nomogram was constructed by incorporating these features.Of the 104 patients included in the study(median age 55 years),75(72.1%)had improved short-term outcomes,while 29(27.9%)showed no signs of improvement.There were numerous differences in clinical characteristics and laboratory findings between patients with improved outcomes and patients without improved outcomes.After a multi-step screening process,prognostic factors were selected and incorporated into the nomogram construction,including immunoglobulin A(IgA),C-reactive protein(CRP),creatine kinase(CK),acute physiology and chronic health evaluation II(APACHE II),and interaction between CK and APACHE II.The C-index of our model was 0.962(95%confidence interval(CI),0.931-0.993)and still reached a high value of 0.948 through bootstrapping validation.A predictive nomogram we further established showed close performance compared with the ideal model on the calibration plot and was clinically practical according to the decision curve and clinical impact curve.The nomogram we constructed is useful for clinicians to predict improved clinical outcome probability for each COVID-19 patient,which may facilitate personalized counselling and treatment.
文摘Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.
基金supported by the Special Fund for Novel Coronavirus Pneumonia from the Department of Science and Technology of Hubei Province(2020FCA035)the Fundamental Research Funds for the Central Universities,Huazhong University of Science and Technology(2020kfyXGYJ023).
文摘Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.
基金supported by a grant from the R&D Program of China(2022YFC2304500).
文摘To the Editor:Hepatitis caused by the hepatitis C virus(HCV)infection has a long course,insidious onset,and slow progression.Patients with hepatitis C are often in the late stages by the time of diagnoses.The long-term chronic damage caused by HCV leads to impaired liver function,portal hypertension,liver fibrosis,cirrhosis and even hepatocellular carcinoma(HCC)[1,2].Therefore,it is imperative to improve the diagnosis and treatment of hepatitis C.In 2016,World Health Organization(WHO)set the goal of“eliminating viral hep-atitis as a public health hazard by 2030”.Some associations intro-duced guidelines for hepatitis C screening and treatment.After a period of effort,in 2020,the number of people receiving treatment for chronic HCV infection had significantly increased compared to the number in 2015,and the HCV-related mortality rate had de-creased.Nevertheless,nearly 80%of infected individuals have not been timely diagnosed and treated[3,4].Like many other coun-tries,China still faces a significant gap in achieving the goal of hep-atitis C elimination,and some literature indicated limited public awareness and high medication costs might slow the progress of policy implementation[5-7].How to effectively improve the diag-nosis and treatment of hepatitis C has garnered widespread global attention.
基金supported by the National Natural Science Foundation of China(82202497)the National Key R&D Program of China(2023YFC2306800)the Fundamental Research Funds for the Central Universities(226-2024-00129).
文摘Hepatitis B virus(HBV)establishes chronic infection through strategic manipulation of host metabolic networks,driving a spectrum of hepatic pathologies ranging from hepatitis to cirrhosis and hepatocellular carcinoma.Mechanistically,HBV reprograms core metabolic pathways,including glycolysis,tricarboxylic acid(TCA)cycle,oxidative phosphorylation,and lipid homeostasis,to fuel its replication machinery and evade immune surveillance.This review systematically synthesizes current evidence on HBV-induced glucose/lipid metabolic rewiring,with particular emphasis on how viral-host crosstalk at the metabolic interface sustains viral pathogenesis.
基金supported by the National Science and Technology Major Project of China(No.2018ZX10302206).
文摘Background PANoptosis has the features of pyroptosis,apoptosis,and necroptosis.Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure(ALF),but limited attention has been given to the crosstalk among them.In this study,we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment.Methods Three ALF-related datasets(GSE14668,GSE62029,and GSE74000)were downloaded from the Gene Expression Omnibus(GEO)database to identify differentially expressed genes(DEGs).Hub genes were identified through intersecting DEGs,genes obtained from weighted gene co-expression network analysis(WGCNA),and genes related to PANoptosis.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein–protein interaction(PPI)analyses and gene set enrichment analysis(GSEA)were performed to determine functional roles.Verification was performed using an ALF mouse model.Results Our results showed that expression of seven hub genes(B-cell lymphoma-2-modifying factor(BMF),B-cell lymphoma-2-interacting protein 3-like(BNIP3L),Caspase-1(CASP1),receptor-interacting protein kinase 3(RIPK3),uveal autoantigen with coiled-coil domains and ankyrin repeats protein(UACA),uncoordinated-5 homolog B receptor(UNC5B),and Z-DNA-binding protein 1(ZBP1))was up-regulated in liver samples of patients.However,in the ALF mouse model,the expression of BNIP3L,RIPK3,phosphorylated RIPK3(P-RIPK3),UACA,and cleaved caspase-1 was up-regulated,while the expression of CASP1 and UNC5B was down-regulated.The expression of ZBP1 and BMF increased only during the development of ALF,and there was no significant change in the end stage.Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers.Western blot results showed that pyroptosis,apoptosis,and necroptosis were always involved in lipopolysaccharide(LPS)/D-galactosamine(D-gal)-induced ALF mice.The ALF cell model showed that bone marrow-derived macrophages(BMDMs)form PANoptosomes after LPS stimulation.Conclusions Our results suggest that PANoptosis of macrophages promotes the development of ALF.The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.
基金supported by the Medical Science and Technology Project of Zhejiang Province(No.2018KY566).
文摘Nuclear factor erythroid 2-related factor 2(Nrf2)is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions.Mitochondria are vital organelles that function in diverse metabolic processes in the body,including redox reactions,lipid metabolism,and cell death.Mitophagy,a specific form of autophagy for damaged mitochondria,plays a critical role in the pathophysiology of liver diseases.In this review,we explain in detail the roles of the Nrf2 signaling pathway and mitophagy,and the relationship between them,in various hepatic diseases(nonalcoholic fatty liver disease,viral hepatitis,alcoholic liver disease,drug-induced liver injury,autoimmune hepatitis,hepatic ischemia-reperfusion injury,and liver cancer).We also offer some potential insights and treatments relevant to clinical applications.
基金funded by National Natural Science Foundation of China(92578123)Shenzhen High-level Hospital Construction Fund(23250G1001)+3 种基金the Sanming Project of Medicine in Shenzhen(SZSM202311033)National Key Research and Development Program of China(2023YFC2606004)National Natural Science Foundation of China(32501262)Beijing Institute of Technology Research Fund Program for Young Scholars(6120220072).
文摘Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.
基金supported by Guangdong Province Basic and Applied Basic Research Fund Project(2023A1515220104)Open Fund of Key Laboratory of Hepatoaplenic Surgery,Ministry of Education(Award Number:GPKF202407).
文摘Objectives:Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia and Philadelphia-like B-cell acute lymphoblastic leukemia(Ph+/Ph-like ALL)constitute the majority of relapsed/refractory B-ALL(R/R B-ALL)cases,highlighting an urgent need to discover new therapeutic targets.This study aims to elucidate the mechanisms underlying poor prognosis in Ph+/Ph-like ALL through transcriptome sequencing and functional cytological assays,with the goal of informing new clinical treatment strategies.Results:Transcriptomic analysis of Ph+/Ph-like ALL patients revealed that low expression of P2X Purinoceptor 1(P2RX1)was associated with unfavorable outcomes.Specifically,patients with poor prognosis and low P2RX1 expression exhibited downregulation of genes involved in energy and calcium metabolism pathways,along with upregulation of genes governing key cellular processes such as cell proliferation(e.g.,MYC),cell cycle progression(e.g.,CCND2),and apoptosis inhibition(e.g.,DASP6).Cellular experiments demonstrated that SUP-B15 cells overexpressing P2RX1 displayed elevated intracellular levels of ATP,calcium,and glucose,together with enhanced glycolytic capacity,compared to empty vector controls.Treatment of SUP-B15 cells with dexamethasone(Dex),Imatinib,or their combination significantly suppressed proliferation and promoted apoptosis,which was accompanied by increases in intracellular ATP,calcium,and glucose.Moreover,exogenous ATP administration(a P2RX1 agonist)enhanced apoptosis and inhibited proliferation in control cells.Conversely,treatment with NF449(a P2RX1 inhibitor)increased proliferation in both P2RX1-overexpressing and control SUP-B15 cells.Conclusion:Our findings indicate that P2RX1 may exert this function through modulating energy metabolism and calcium homeostasis,resulting in elevated intracellular calcium levels.Sustained elevation of calcium promotes apoptosis,whereas exogenous ATP activates P2RX1,enhances calcium influx,and attenuates the suppression of apoptosis associated with P2RX1 underexpression,ultimately correlating with improved treatment response.
基金supported by grants from the Science&Technology Key Program of Zhejiang China(2017C03051)the National Science&Technology Major Project of China(2017ZX10203201)。
文摘Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.
基金Supported by National Science and Technology Major Project of China,No.2018ZX10302206.
文摘The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.
基金Supported by Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control,No.2020XGZX052.
文摘In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.
基金Supported by the National Science and Technology Major Project of China,No.2018ZX10302206 and No.2017ZX10202203-007-010。
文摘γδT cells are unconventional T lymphocytes that bridge innate and adaptive immunity.Based on the composition of T cell receptor and the cytokines produced,γδT cells can be divided into diverse subsets that may be present at different locations,including the liver,epithelial layer of the gut,the dermis and so on.Many of these cells perform specific functions in liver diseases,such as viral hepatitis,autoimmune liver diseases,non-alcoholic fatty liver disease,liver cirrhosis and liver cancers.In this review,we discuss the distribution,subsets,functions ofγδT cells and the relationship between the microbiota andγδT cells in common hepatic diseases.AsγδT cells have been used to cure hematological and solid tumors,we are interested inγδT cell-based immunotherapies to treat liver diseases.
基金by a National Key Science and Technology Project of China(2018YFC2000500,03)the National Natural Science Foundation of China(81790631 and 81703430)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-045)。
文摘Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology.Also,microbiome-based therapies have been used to improve health status and treat diseases.In addition,aging and neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease,have become topics of intense interest in biomedical research.Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease.But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear.As technology advances,new techniques for studying the microbiome will be developed and refined,and the relationship between diseases and gut microbiota will be revealed.This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases,highlighting assay techniques for the gut microbiome,and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.
基金Chinese High Tech Research&Development(863)Program,No.2013AA020102.
文摘BACKGROUND Hepatorenal syndrome(HRS)is a severe complication of cirrhosis with high mortality,which necessitates accurate clinical decision.However,studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough.Meanwhile,a multicenter cohort study with a long span of time could be more convincing.AIM To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors.METHODS We retrospectively enrolled 1667 patients from four hospitals,and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS.Characteristics were compared between survivors and non-survivors,and potential prognostic factors were selected according to the impact on 28-d mortality.Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems,including Model for End-Stage Liver Disease(MELD),Chronic Liver Failure-Sequential Organ Failure Assessment(CLIF-SOFA),and Chinese Group on the Study of Severe Hepatitis BAcute-on-Chronic Liver Failure(COSSH-ACLF).RESULTS Five prognostic factors,comprised of gender,international normalized ratio,mean corpuscular hemoglobin concentration,neutrophil percentage,and stage,were integrated into a new score,GIMNS;stage is a binary variable defined by the number of failed organs.GIMNS was positively correlated with MELD,CLIFSOFA,and COSSH-ACLF.Additionally,it had better accuracy[area under the receiver operating characteristic curve(AUROC):0.830]than MELD(AUROC:0.759),CLIF-SOFA(AUROC:0.767),and COSSH-ACLF(AUROC:0.759)in the derivation cohort(P<0.05).It performed better than MELD and CLIF-SOFA in the validation cohort(P<0.050)and had a higher AUROC than COSSH-ACLF(P=0.122).CONCLUSION We have developed a new scoring system,GIMNS,to predict 28-d mortality of HRS patients.Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS.Additionally,the GIMNS score showed better accuracy than MELD and CLIF-SOFA,and the AUROC was higher than that of COSSH-ACLF.
文摘Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases,injury repair,degenerative diseases,and tumors.Exosomes are small vesicles rich in a variety of nucleic acids[including messenger RNA,Long non-coding RNA,microRNA(miRNA),and circular RNA],proteins,and lipids.Exosomes can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between cells.Like exosomes,miRNAs were neglected before their role in various activities of organisms was discovered.Several studies have confirmed that miRNAs play a vital role within exosomes.This review focuses on the specific role of miRNAs in MSC-derived exosomes(MSC-exosomes)and the methods commonly used by researchers to study miRNAs in exosomes.Taken together,miRNAs from MSC-exosomes display immense potential and practical value,both in basic medicine and future clinical applications,in treating several diseases.
基金supported by the National Key Research and Development Program of China (2017YFC1600100 and2017YFC1200203)the National Natural Science Foundation of China (81702040)the National Science Foundation of Zhejiang Province,China (LY20H190002)
文摘Humanity is facing an enormous and growing worldwide threat from the emergence of multi-drug-resistant(MDR)Gram-negative bacteria such as Escherichia coli,Klebsiella pneumoniae,and Acinetobacter baumannii.Polymyxin B and E(colistin)constitute the last-line therapies for treating MDR Gram-negative bacteria.Polymyxin is a cationic antibacterial peptide that can destroy the outer membrane of Gram-negative bacteria.With the increasing clinical application of polymyxin,however,there have been many reports of the occurrence of polymyxin-resistant Gram-negative bacteria.This resistance is mainly mediated by the modification or complete loss of lipopolysaccharide(LPS).LPS is also a virulence factor of Gram-negative bacteria,and alterations of LPS may correlate with virulence.Although it is generally believed that the biological costs associated with drug resistance may enable benign susceptible bacteria to overcome resistant bacteria when antibiotic pressure is reduced,some studies have shown that polymyxin-resistant bacteria are associated with higher virulence and greater fitness compared with their susceptible counterparts.To predict the development of polymyxin resis-tance and evaluate interventions for its mitigation,it is important to understand the relative biological cost of polymyxin resistance compared with susceptibility.The impact of polymyxin resistance mecha-nisms on the virulence and fitness of these three Gram-negative bacteria are summarized in this review.
