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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

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Hepatobiliary & Pancreatic diseases International 2024年第1期23卷 43-51页

作者： Qing-Qi Zhang Qian Chen Pan Cao Chun-Xia Shi Lu-Yi Zhang Lu-Wen Wang Zuo-Jiong Gong department of infectious diseases Renmin Hospital of Wuhan UniversityWuhan 430060China

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical *** pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ ***:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+*** L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA *** liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also *** endoplasmic reticulum membranes(MAMs)were measured by ***:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 *** comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 *** levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 *** with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA ***2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 *** observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced gr

关键词： SIRT2 inhibitor AGK2 Acute liver failure MFN2 Ferroptosis

Causal Relationship Between Gut Microbiota and Liver Cirrhosis:16S rRNA Sequencing and Mendelian Randomization Analyses

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 123-133页

作者： Mengqin Yuan Xue Hu Lichao Yao Ping Chen Zheng Wang Pingji Liu Zhiyu Xiong Yingan Jiang Lanjuan Li department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubeiChina State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Centre for Infectious DiseasesCollaborative Innovation Centre for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Background and Aims:Accumulating evidence highlights the association between the gut microbiota and liver ***,the role of the gut microbiota in liver cirrhosis remains ***:We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA *** then performed a two-sample Mendelian randomization(MR)analysis to reveal the underlying causal relationship between the gut microbiota and liver *** relationships were analyzed using primary inverse variance weighting(IVW)and other supplemental MR ***,fecal samples from liver cirrhosis patients and healthy controls were collected to validate the results of the MR ***:Analysis of 16S rRNA sequencing indicated significant differences in gut microbiota composition between the cirrhosis and control *** analyses suggested that Alphaproteobacteria,Bacillales,NB1n,Rhodospirillales,Dorea,Lachnospiraceae,and Rhodospirillaceae were positively correlated with the risk of liver cirrhosis,whereas Butyricicoccus,Hungatella,Marvinbryantia,and Lactobacillaceae displayed the opposite ***,the weighted median and MR-PRESSO estimates further showed that only Butyricicoccus and Marvinbryantia presented stable negative associations with liver *** significant heterogeneity or horizontal pleiotropy was observed in the sensitivity ***,the result of 16S rRNA sequencing also showed that healthy controls had a higher relative abundance of Butyricicoccus and Marvinbryantia than liver cirrhosis ***:Our study provides new causal evidence for the link between gut microbiota and liver cirrhosis,which may contribute to the discovery of novel strategies to prevent liver cirrhosis.

关键词： 16S rRNA gene sequencing Liver cirrhosis Gut microbiota Causality Two-sample Mendelian randomization study

Polylactic acid micro/nanoplastic-induced hepatotoxicity: Investigating food and air sources via multi-omics

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Environmental Science and Ecotechnology 2024年第5期21卷 294-308页

作者： Hua Zha Shengyi Han Ruiqi Tang Dan Cao Kevin Chang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina department of Statistics The University of AucklandAucklandNew Zealand

Micro/nanoplastics(MNPs)are detected in human liver,and pose significant risks to human *** exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse ***,nasal exposure to non-biodegradable plastics can cause airway dysbiosis in ***,the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly *** we show the hepatotoxic effects of biodegradable polylactic acid(PLA)MNPs through multi-omics analysis of various biological samples from mice,including gut,fecal,nasal,lung,liver,and blood *** results show that both foodborne and airborne PLA MNPs compromise liver function,disrupt serum antioxidant activity,and cause liver ***,foodborne MNPs lead to gut microbial dysbiosis,metabolic alterations in the gut and serum,and liver transcriptomic *** MNPs affect nasal and lung microbiota,alter lung and serum metabolites,and disrupt liver *** gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure,while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP *** relevant results suggest that foodborne PLA MNPs could affect the“gut microbiota-gutliver”axis and induce hepatoxicity,while airborne PLA MNPs could disrupt the“airway microbiota-lungliver”axis and cause *** findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the *** current study could be a starting point for biodegradable MNPs-induced *** research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

关键词： Micro/nanoplastics Hepatotoxicity Microbiota dysbiosis Metabolic disruption Transcriptomic dysregulation

A real-world study of the differences in Traditional Chinese Medicine diagnosis and treatment rules for coronavirus disease 2019 between Northern and Southern China

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Journal of Traditional Chinese Medicine 2024年第4期44卷 822-829页

作者： SU Rui SU Youzhu WANG Shuo FAN Jie LIU Qingquan LIU Mifeng department of infectious diseases Capital Medical University Beijing Hospital of Traditional Chinese MedicineBeijing 100010China

OBJECTIVE:To explore the differences in Traditional Chinese Medicine(TCM)diagnosis and treatment rules for coronavirus disease 2019(COVID-19)between Northern and Southern China based on the real-world data from 982 COVID-19 ***:All consecutive cases of COVID-19 admitted to the TCM department of designated COVID-19 hospitals in eight provinces and cities were retrospectively *** were divided into a Northern and a Southern group according to the location of the admitting *** symptoms,syndrome elements,syndrome distribution and herbal treatments were *** core prescriptions were extracted using the multiscale backbone-based network comparison algorithm(msbNC).RESULTS:The distribution of syndrome elements showed that dampness was common in Northern and Southern China,wind and heat were more often present in the South,while fire toxin and spleen deficiency were more often encountered in the *** distribution of syndromes showed that the South was dominated by heat dampness accumulating in the lung(55.69%),while the North was dominated by dampness-toxin stagnating in the lung(44.90%).The results of core prescription mining showed that dispelling dampness,dispersing wind,clearing heat and strengthening spleen were the common treatment methods in Northern and Southern *** mild cases,Jinyinhua(Flos Lonicerae)and Lianqiao(Fructus Forsythiae Suspensae)were often used in the South to clear heat and relieve exterior symptoms,while Chaihu(Radix Bupleuri Chinensis)and Huangqin(Radix Scutellariae Baicalensis)were often used in the North to relieve muscles by expelling *** moderate cases,Chaihu(Radix Bupleuri Chinensis),Qinghao(Herba Artemisiae Annuae),and Shigao(Gypsum Fibrosum)were often used to clear heat of Tri-jiao Channel and stomach in the South,while Fuling(Poria),Chenpi(Pericarpium Citri Reticulatae),and Dangshen(Radix Codonopsis)were often used to invigorate spleen and remove dampness in the *** severe cases

关键词： COVID-19 medicine,Chinese traditional North-South difference core prescription syndrome retrospective studies

Metabolic Dysregulation and Metabolite Imbalances in Acuteon-chronic Liver Failure:Impact on Immune Status

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 865-877页

作者： Danmei Zhang Chunxia Shi Yukun Wang Jin Guo Zuojiong Gong department of infectious diseases Renmin Hospital of Wuhan UniversityWuhanHubeiChina

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function,triggered by factors both within and outside the *** the definition of acute-on-chronic liver failure(ACLF)may vary by region,it is universally recognized for its association with multiorgan failure,a robust inflammatory response,and high short-term mortality *** advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ***,immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell ***,understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for *** review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions,offering novel perspectives for immune regulation and therapeutic management of liver failure.

关键词： Acute-on-chronic liver failure Immunometabolism Metabolism Metabolic reprogramming Metabolomics Microenvironment

Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

Detection of HBV DNA integration in plasma cell-free DNA of different HBV diseases utilizing DNA capture strategy

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Virologica Sinica 2024年第4期39卷 655-666页

作者： Zerui Yang Jingyan Zeng Yueyue Chen Mengchun Wang Hongchun Luo Ai-Long Huang Haijun Deng Yuan Hu Key Laboratory of Molecular Biology on infectious diseases Ministry of EducationChongqing Medical UniversityChongqing400016China department of infectious diseases The First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China

The landscape of hepatitis B virus(HBV)integration in the plasma cell-free DNA(cfDNA)of HBV-infected patients with different stages of liver diseases[chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC)]remains *** this study,we developed an improved strategy for detecting HBV DNA integration in plasma cfDNA,based on DNA probe capture and next-generation *** this optimized strategy,we successfully detected HBV integration events in chimeric artificial DNA samples and HBV-infected HepG2-NTCP cells at day one post infection,with high sensitivity and *** characteristics of HBV integration events in the HBV-infected HepG2-NTCP cells and plasma cfDNA from HBV-infected individuals(CHB,LC,and HCC)were further investigated.A total of 112 and 333 integration breakpoints were detected in the HepG2-NTCP cells and 22 out of 25(88%)clinical HBV-infected samples,*** vivo analysis showed that the normalized number of support unique sequences(nnsus)in HCC was significantly higher than in CHB or LC patients(P values<0.05).All integration breakpoints are randomly distributed on human chromosomes and are enriched in the HBV genome around nt *** majority of integration breakpoints(61.86%)are located in the gene-coding *** non-homologous end-joining(NHEJ)and microhomology-mediated end-joining(MMEJ)interactions occurred during HBV integration across the three different stages of liver *** study provides evidence that HBV DNA integration can be detected in the plasma cfDNA of HBV-infected patients,including those with CHB,LC,or HCC,using this optimized strategy.

关键词： Hepatitis B virus(HBV) DNA integration Cell-free DNA(cfDNA) DNA capture

Dengue hemorrhagic fever with rectus sheath hematoma:A case report

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Asian Pacific Journal of Tropical Medicine 2024年第3期17卷 136-138页

作者： Boudhayan Bhattacharjee Hardik Patel Rucha Karad Vasireddy Teja Agnibho Mondal Soumendra Nath Haldar Bibhuti Saha department of infectious diseases and Advanced Microbiology School of Tropical MedicineKolkataIndia

Rationale:Acute pain is a medical emergency that requires prompt abdominal evaluation and ***,a mosquito-borne arboviral infection,can lead to complications such as acute abdominal *** concerns:A 72-year-old hypertensive female presented with high-grade intermittent fever with chills and rigors for four *** was diagnosed with dengue fever(NS1Ag-reactive)the day before admission.A contrast-enhanced computed tomography of the abdomen showed a hematoma along the rectus sheath which was managed conservatively as per surgical ***:Dengue hemorrhagic fever with rectus sheath ***:Blood transfusion and fluid ***:Ten days after discharge,the patient reproted no pain in the right iliac fossa and the size of the hematoma was significantly ***:Although it is rarely seen as a cause of acute abdomen,complaints of adnominal pain should never be ignored in critical or convalescent phase of dengue *** investigations should be promptly conducted as hematoma is often difficult to be diagnosed *** in diagnosis of rectus sheath hematoma can be fatal.

关键词： Dengue fever Rectus sheath hematoma Surgical emergency Acute appendicitis