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metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma

Acta Pharmaceutica Sinica B 2022年第2期12卷 558-580页

作者： Danyu Du Chan Liu Mengyao Qin Xiao Zhang Tao Xi Shengtao Yuan Haiping Hao Jing Xiong Department of Pharmacology School of PharmacyChina Pharmaceutical UniversityNanjing 210009China Research Center of Biotechnology School of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 210009China Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityNanjing 210009China

Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence *** efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of ***,limitations exist in current strategies including chemoresistance for *** initiation and progression is driven by reprogramming of metabolism,in particular during HCC ***,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC *** this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical *** also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC ***,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.

关键词： metabolic dysregulation Hepatocellular carcinoma Glycolysis Tricarboxylic acid cycle Pentose phosphate pathway Fatty acidβ-oxidation Glutamine metabolism Cancer therapy

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Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners:A metabolic and bacteriological investigation in Escherichia coli

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Frontiers of Environmental Science & Engineering 2022年第9期16卷 53-64页

作者： Shuqin Liu Rui Wu Xi Yang Shuting Fang Zhangmin Xiang Shenghong Yang Gangfeng Ouyang Guangdong Provincial Key Laboratory of Chemical Measurement and Emergency Test Technology Guangdong Provincial Engineering Research Center for Ambient Mass SpectrometryInstitute of AnalysisGuangdong Academy of Sciences(China National Analytical Center Guangzhou)Guangzhou 510070China Shandong Provincial Key Laboratory of Molecular Engineering School of Chemistry and Chemical EngineeringQilu University of Technology(Shandong Academy of Sciences)Jinan 250353China KLGHEI of Environment and Energy Chemistry School of ChemistrySun Yat-sen UniversityGuangzhou 510275China

Incomplete separation and recycling of nanoparticles are causing undesirable nanopollution and thus raising great concerns with regard to *** microorganisms are important regulator of physiological processes in many organisms,the interaction between nanopollution and microbial metabolomics and the resultant impact on the host’s health are important but *** investigate how typical nanopollution perturbs microbial growth and metabolism,Escherichia coli(***)in vitro was treated with six water-dispersible nanomaterials(nanoplastic,nanosilver,nano-TiO 2,nano-ZnO,semiconductor quantum dots(QDs),carbon dots(CDs))at human-/environment-relevant concentration *** nanomaterials exhibited type-specific toxic effects on *** *** metabolite profiling was used to characterize metabolic disruption patterns in the model microorganism exposed to different *** percentage of significant metabolites(p1)accounted for 6%–38%of the total 293 identified metabolites in each of the nanomaterial-contaminated bacterial *** results also exhibited significant differences between different nanopollutants and dose levels,revealing type-specific and untypical concentration-dependent metabolic *** metabolites responsive to nanopollution exposures were mainly involved in amino acid and purine metabolisms,where 5,4,and 7 significant metabolic features were included in arginine and proline metabolism,phenylalanine metabolism,and purine metabolism,*** conclusion,this study horizontally compared and demonstrated how typical nanopollution perturbs microbial growth and metabolomics in a type-specific manner,which broadens our understanding of the ecotoxicity of nanopollutants on microorganisms.

关键词： Nano-toxicity Nano-plastics Quantum dots Microbial metabolite metabolic dysregulation

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Comparative associations of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease with risk of incident chronic kidney disease:a cohort study

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 801-813,I0003-I0005页

作者： Ji Hye Heo Mi Yeon Lee Seong Hwan Kim Ming-Hua Zheng Christopher D.Byrne Giovanni Targher Ki-Chul Sung Department of Internal Medicine Hallym University College of MedicineChuncheonRepublic of Korea Division of Biostatistics Department of R&D ManagementKangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea Division of Cardiology Department of Internal MedicineKorea University Ansan HospitalAnsanRepublic of Korea MAFLD Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Wenzhou Key Laboratory of Hepatology WenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouChina Nutrition and Metabolism Faculty of MedicineUniversity of SouthamptonSouthamptonUK Southampton National Institute for Health and Care Research Biomedical Research CentreUniversity Hospital SouthamptonSouthamptonUK metabolic Diseases Research Unit IRCCS Sacro Cuore-Don Calabria HospitalNegrar di ValpolicelleItaly Division of Cardiology Department of Internal MedicineKangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea

Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney disease(CKD)and abnormal ***:We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver *** were further subdivided into no steatotic liver disease(no-SLD),NAFLD-only,MASLD-only,both NAFLD and MASLD,and SLD not categorized as NAFLD or MASLD *** proportional hazards models were used to analyze the risk of incident CKD and ***:Compared with either the no-NAFLD or no-MASLD groups,the NAFLD and MASLD groups were associated with a higher risk of incident CKD(NAFLD:adjusted hazard ratio(HR),1.18[95%CI,1.01-1.38];MASLD:adjusted HR,1.21[95%CI,1.04-1.39]).Among the five subgroups,both NAFLD and MASLD group had the strongest association with risk of incident CKD(adjusted HR,1.21[95%CI,1.04-1.42]).The MASLD-only group had the strongest association with incident abnormal albuminuria,with an adjusted HR comparable to that of the both NAFLD and MASLD group(adjusted HR 1.96[95%CI,1.44-2.67]for the MASLD-only,and adjusted HR 1.98[95%CI,1.58-2.49]for the both NAFLD and MASLD group versus the no-SLD group).The NAFLD-only group was not independently associated with risk of CKD or abnormal ***:These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.

关键词： metabolic dysregulation non-alcoholic fatty liver disease(NAFLD) metabolic syndrome chronic kidney disease(CKD) albuminuria

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