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Infectious Microbes & Diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen 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

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses *** following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation *** were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV *** analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS *** IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating ***,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two *** data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy

Lactobacillus plantarum AR113 attenuates liver injury in D-galactose-induced aging mice via the inhibition of oxidative stress and endoplasmic reticulum stress

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Food Science and Human Wellness 2024年第2期13卷 885-897页

作者： Yongjun Xia Yujie Gong Xiangna Lin Yijin Yang Xin Song Guangqiang Wang Zhiqiang Xiong Yangyang Qian Zhuan Liao Hui Zhang Lianzhong Ai School of Health Science and Engineering Shanghai Engineering Research Center of Food MicrobiologyUniversity of Shanghai for Science and TechnologyShanghai 200093China College of Life Sciences Linyi UniversityLinyi 276000China Department of Gastroenterol. Digestive Endoscopy CenterChanghai HospitalShanghai 200082China

Probiotics could effectively eliminate excess reactive oxygen species(ROS)generated during aging or lipid metabolism disorders,but their mechanism is *** major purpose of this study was to investigate the mechanism of Lactiplantibacillus plantarun AR113 alleviating oxidative stress injury in the D-galactose induced aging *** result showed that pretreatment with *** AR113 significantly relieving H_(2)O_(2)induced cytotoxicity in HepG2 cells by maintain cell membrane integrity and increasing antioxidant enzyme *** D-galactose induced aging mice,*** AR113 could significantly attenuate liver damage and inflammatory infiltration by promoting endogenous glutathione(GSH)synthesis and activating the Nrf2/Keap1 signaling pathway in mice,and increasing the expression of regulated phaseⅡdetoxification enzymes and antioxidant *** analysis shown that gavage of *** AR113 could significantly reduce the expression of G protein-coupled receptor 78(GPR78)and C/EBP homologous protein(CHOP)proteins,and promote the restoration of endoplasmic reticulum(ER)homeostasis,thereby activating cell anti-apoptotic *** results were also confirmed in H_(2)O_(2)-treated HepG2 *** indicated that *** AR113 could inhibit D-galactose-induced liver injury through dual inhibition of ER stress and oxidative *** AR113 have good application potential in anti-aging and alleviating metabolic disorders.

关键词： Lactiplantibacillus plantarun AR113 HepG2 D-galactose Oxidative stress ER stress

Pre-MASLD:Should it be defined separately?

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 1-3页

作者： Hang-Kai Huang You-Ming Li Cheng-Fu Xu Department of Gastroenterology Zhejiang Provincial Clinical Research Center for Digestive Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases,yet it has not received sufficient attention[1].Over the past two decades,the overall global prevalence of NAFLD has risen from 25%to 37%[2].The disease burden of NAFLD is fueled by the epidemic of obesity and diabetes[3].It is estimated that more than half of patients with diabetes have NAFLD.

关键词： NAFLD liver diseases

Elevated Kallistatin promotes the occurrence and progression of non-alcoholic fatty liver disease

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1730-1744页

作者： Zhenzhen Fang Gang Shen Yina Wang Fuyan Hong Xiumei Tang Yongcheng Zeng Ting Zhang Huanyi Liu Yanmei Li Jinhong Wang Jing Zhang Anton Gao Weiwei Qi Xia Yang Ti Zhou Guoquan Gao Department of Biochemistry Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China Department of VIP Medical center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Physical Examination center the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Clinical Laboratory Guangzhou First People's HospitalGuangzhou 510080China Guangdong Key Laboratory of liver Disease research the Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 51008China Department of Health Sciences College of Health SolutionsArizona State UniversityTempeUSA Guangdong Engineering&Technology research center for Gene Manipulation and Biomacromolecular Products Sun Yat-Sen UniversityGuangzhou 510080China Guangdong Province Key Laboratory of Diabetology Guangzhou 510o80China Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic ***(HLP)is the leading risk factor for *** study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were *** plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver ***,KAL levels of NAFLD patients were significantly *** transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)*** contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD ***,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),***-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa ***,hepatic CGl-58-overexpress reverses NASH in KAL transgenic ***,free fatty acids up-regulated KAL against thyroid hormone in ***,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating *** results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.

关键词： GSK3β inflammation elevated

Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

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Animal Models and Experimental Medicine 2024年第2期7卷 166-178页

作者： Xuecui Yin Lin Dong Xiaohan Wang Zhenzhen Qin Yuying Ma Xiaofei Ke Ya Li Qingde Wang Yang Mi Quanjun Lyu Xia Xu Pengyuan Zheng Youcai Tang Department of Internal Medicine the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Pediatrics the Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Clinical Nutrition the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaCo-innovation Center of Henan Province for New drug R&D and Preclinical SafetySchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina Department of Pediatrics GastroenterologyHenan Key Laboratory of Rehabilitation MedicineHenan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Studiothe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases *** stellate cells(HSCs)are the major effector cells of liver *** contain abundant lipid droplets(LDs)in their cytoplasm during *** 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid ***,little is known about the role of PLIN 5 in HSC ***:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus *** the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in *** corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy *** analysis of mice liver tissue metabolism was performed based on UPLC-MS/***,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and ***:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK *** addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver ***:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

关键词： AMPK apoptosis hepatic stellate cell liver fibrosis perilipin 5

Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell-and metabolism-based fast-screening model

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Journal of Environmental Sciences 2024年第3期137卷 370-381页

作者： Shuxian Zhang Miaomiao Zhao Shichang Li Renjun Yang Nuoya Yin Francesco Faiola State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China

In recent years,neonicotinoids(NEOs)and organophosphate esters(OPEs)have been widely used as substitutes for traditional pesticides and brominated fame-retardants,*** studies have shown that those compounds can be frequently detected in environmental and human samples,are able to penetrate the placental barrier,and are toxic to ***,it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans,especially during *** employed a human embryonic stem cell differentiation-and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of *** show that four NEO and five OPE prototypes targeted mostly ectoderm specification,as neural ectoderm and neural crest genes were down-regulated,and surface ectoderm and placode markers *** liver S9 fraction's treatment could generally reduce the effects of the chemicals,except in a few specific instances,indicating the liver may detoxify NEOs and *** findings suggest that NEOs and OPEs interfere with human early embryonic development.

关键词： Neonicotinoids Organophosphate esters Human embryonic stem cells Fast screening model Developmental toxicity

N-glycosylation of Wnt3 regulates the progression of hepatocellular carcinoma by affecting Wnt/β-catenin signal pathway

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2769-2780页

作者： Xin-Zhan Zhang Xiao-Chuan Mo Zhu-Ting Wang Rong Sun Da-Quan Sun Department of Biochemistry and Molecular Biology&research center for Basic Medical Sciences Guizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

BACKGROUND Wnt/FZD-mediated signaling pathways are activated in more than 90%of hepatocellular carcinoma(HCC)cell *** a well-known secretory glycoprotein,Wnt3 can interact with FZD receptors on the cell surface,thereby activating the Wnt/β-catenin signaling ***,the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still *** To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC *** Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites,actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation,the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy,and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/β-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function *** Wnt3 has two N-glycosylation-modified sites(Asn90 and Asn301);when a single site at amino acid 301 is mutated,the stability of Wnt3 is weakened;the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously;and the level of proteins related to the Wnt/β-catenin signaling pathway is *** proliferation,migration and invasion are also weakened in the case of single 301 site and double-site *** These results indicate that by inhibiting the N-glycosylation of Wnt3,the proliferation,migration,invasion and colony formation abilities of liver cancer cells can be weakened,which might provide new therapeutic strategies for clinical liver cancer in the future.

关键词： Wnt3 N-glycosylation Hepatocellular carcinoma liver cancer Wnt/β-catenin FZD7

Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

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World Journal of Gastroenterology 2024年第17期30卷 2343-2353页

作者： Oraphan Jitpraphawan Witchakorn Ruamtawee Mala Treewatchareekorn Supatsri Sethasine Division of Gastroenterology and Hepatology Department of MedicineNavamindradhiraj UniversityDusit 10300BangkokThailand Clinical research center Research Facilitation DivisionNavamindradhiraj UniversityDusit 10300BangkokThailand Division of Clinical Chemistry and Immunology Navamindradhiraj UniversityDusit 10300BangkokThailand

BACKGROUND The GALAD score has improved early hepatocellular carcinoma(HCC)detection *** role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular *** To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum *** This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira *** patients had HCC staging allocation using the Barcelona Clinic liver Cancer(BCLC)***,HCC etiology,and HCC features were *** and the GALAD score were obtained at *** performance of the GALAD score and biomarkers were prospectively *** Exactly 115 individuals were diagnosed with *** GALAD score increased with disease *** BCLC-0/A and BCLC-B/C/D,the GALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the GALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of GALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of GALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year *** The GALAD model can diagnose HCC at the curative stage,includin

关键词： Alpha-fetoprotein Barcelona clinic liver cancer GALAD score Hepatocellular carcinoma Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein Protein induced by vitamin K absence-II

Mechanism of action of the bile acid receptor TGR5 in obesity

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Acta Pharmaceutica Sinica B 2024年第2期14卷 468-491页

作者： Weijun Lun Qihao Yan Xinghua Guo Minchuan Zhou Yan Bai Jincan He Hua Cao Qishi Che Jiao Guo Zhengquan Su Guangdong Engineering research center of Natural Products and New Drugs Guangdong Provincial University Engineering Technology Research Center of Natural Products and DrugsGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Metabolic Disease research center of Integrated Chinese and Western Medicine Key Laboratory of Glucolipid Metabolic DisorderMinistry of Education of ChinaGuangdong TCM Key Laboratory for Metabolic DiseasesGuangdong Pharmaceutical UniversityGuangzhou 510006China School of Public Health Guangdong Pharmaceutical UniversityGuangzhou 510310China School of Chemistry and Chemical Engineering Guangdong Pharmaceutical UniversityZhongshan 528458China Guangzhou Rainhome Pharm&Tech Co. Ltd.Science CityGuangzhou 510663China

G protein-coupled receptors(GPCRs)are a large family of membrane protein receptors,and Takeda G protein-coupled receptor 5(TGR5)is a member of this *** a membrane receptor,TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism,including the processes of energy consumption,weight loss and blood glucose *** studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver,obesity and *** the global obesity situation becoming more and more serious,a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently *** this review,we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target,and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands,which can effectively provide new ideas for ligand research and promote drug research.

关键词： Obesity TGR5 Bile acids Ligand Appetite Metabolism GLP-1 Inflammation