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Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: therapeutic potential for liver fibrosis

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Genes & Diseases 2023年第2期10卷 480-494页

作者： Harsh Vardhan Charan Durgesh Kumar Dwivedi Sabbir Khan Gopabandhu Jena Facility for Risk Assessment and intervention Studies Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and ResearchSector-67S.A.S. NagarPunjab 160062India Department of Neuro-Oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

The liver injury leads to an inflammatory response, which causes the activation of hepatic stellate cells (HSCs) that further secrete ECM proteins and play an important role in liver fibrosis. Moreover, the inflammatory response is a driving force for fibrogenesis, which is triggered by many types of injuries. Exaggerated inflammatory immune responses are mediated by cytoplasmic protein complexes known as inflammasomes, which are involved in many chronic liver diseases. Inflammasomes are pattern recognition receptors (PRRs) that can sense any microbial motifs known as pathogen-associated molecular patterns (PAMPs), and host- or environmental-derived stress signals known as damage-associated molecular patterns (DAMPs). The inflammasomes cause caspase-mediated proteolytic cleavage of pro-IL-1β and pro-IL-18 into active IL-1β and IL-18. In this review, we provide a comprehensive summary of the important roles of NLRP3 inflammasome in the pathogenesis of liver fibrosis with an emphasis on several direct and indirect pathways responsible for the NLRP3 inflammasome-mediated HSCs activation and fibrogenesis. In addition, we discuss the general pharmacological and genetics strategies for the inhibition of NLRP3 inflammasome activation and its downstream signaling with examples of emerging pharmacotherapeutics, targeting the NLRP3 inflammasome signaling as well as a possible way to develop effective and safer NLRP3 inflammasome inhibitors.

关键词： Hepatic stellate cells Liver fibrosis NLRP3 activation NLRP3 inflammasome NLRP3 inhibitors

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Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong Hao Li Peng Liao Long Chen Yao Pan Yongqiang Zheng Changqing Zhang Delin Liu Minghao Zheng Junjie Gao centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s Hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace

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Synaptic dysfunction in Alzheimer's disease:the effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention

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Neural Regeneration Research 2018年第4期13卷 616-623页

作者： Jade Marsh Pavlos Alifragis centre for Biomedical Sciences School of Biological SciencesRoyal Holloway University of London

The most prevalent form of dementia in the elderly is Alzheimer＇s disease.A significant contributing factor to the progression of the disease appears to be the progressive accumulation of amyloid-β42（Aβ42）,a small hydrophobic ***,attempts to develop therapies targeting the accumulation of Aβ42 have not been successful to treat or even slow down the *** is possible that this failure is an indication that targeting downstream effects rather than the accumulation of the peptide itself might be a more effective *** accumulation of Aβ42 seems to affect various aspects of physiological cell *** this review,we provide an overview of the evidence that implicates Aβ42 in synaptic dysfunction,with a focus on how it contributes to defects in synaptic vesicle dynamics and neurotransmitter *** discuss data that provide new insights on the Aβ42 induced pathology of Alzheimer＇s disease and a more detailed understanding of its contribution to the synaptic deficiencies that are associated with the early stages of the *** the precise mechanisms that trigger synaptic dysfunction are still under investigation,the available data so far has enabled us to put forward a model that could be used as a guide to generate new therapeutic targets for pharmaceutical intervention.

关键词： Alzheimer's disease amyloid-β 42 synaptic vesicles synaptic dysfunction neurotransmitter release

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Prognostic value of ultrasound in early arterial complications post liver transplant

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 13-20页

作者： Ning-Bo Zhao Yi Chen Rui Xia Jian-Bo Tang Dong Zhao Department of Ultrasound National Clinical Research Centre for Infectious DiseaseShenzhen Third People's HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518112Guangdong ProvinceChina Department of Thyroid and Hernia Surgery The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen 51800Guangdong ProvinceChina Department of Liver Surgery and Organ Transplantation Center Shenzhen Third People's HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518112Guangdong ProvinceChina

Liver transplantation is the primary therapeutic intervention for end-stage liver ***,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** clinical manifestations associated with early arterial complications following liver transplantation are often *** timely intervention,these complications can result in graft fai-lure or patient ***,early diagnosis and the formulation of an op-timal treatment plan are *** examination remains the pre-dominant imaging modality for detecting complications post liver *** article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these ***,ultrasound offers the advantages of convenience,safety,effect-iveness,and *** enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation *** Liver transplantation stands as the primary therapeutic approach for end-stage liver *** advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation *** these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood *** later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood *** is now understood that the establishment of effective collat

关键词： Liver transplantation Vascular complication Arterial complication Ultrasound

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therapeutic Effect of Transcatheter Arterial Chemoembolization Combined with Percutaneous Ethanol Injection in Hepatocellular Carcinoma

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The Chinese-German Journal of Clinical Oncology 2002年第1期1卷 28-29页

作者： QU Zengqiang, QIAN Guojun, CHEN Han Department of intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China Department of intervention Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai China

Objective To evaluate the clinical efficacy of the combined treatment with transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) on hepatocellular carcinoma (HCC) .Methods 312 patients with moderate or advanced HCCs were divided into two groups; 170 cases underwent TACE treatment alone, 142 cases were treated with TACE and PEI under B-ultrasound guidance.Results The rates of reduction in tumor diameter and the decline in serum AFP level were 41.2% and 40.4% in the TACE group and 75.4% and 74.1 % in the TACE + PEI group respectively. The 6, 12 and 24 months survival rates in the TACE group were 77.1 % , 34.1% and 18.8% ,respectively and in the TACE + PEI group 87.3% , 62.0% and 38.0% , respectively. Overall, there was a significant difference between the two treatment groups ( P < 0.05). Conclusion Treatment on HCCs with TACE + PEI is convenient, safe and results in better survival rates than TACE alone.

关键词： neoplasm hepatocellular embolization ethanol ultrasound guided intervention

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The history of interventional therapy for liver cancer in China

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Journal of interventional Medicine 2018年第2期1卷 70-76页

作者： Mengxuan Zuo Jinhua Huang Department of Minimally Invasive intervention Sun Yat-sen University Cancer Center State Key Laboratory Of Oncology In South China

In China interventional therapy of liver cancer started in the 1980s. It is well-known that Professor Lin Gui is the founding father of interventional radiology. Under the leadership of Lin Gui and other professors, interventional therapy of liver cancer has swiftly progressed in China. Indeed, TAI, TAE, TACE and ablation therapy have witnessed great innovations in hardware facil ities, technical means, and therapeutic philosophy, while incorporating Chinese characteristics. As with the development of combined interventional therapy in China, interventional treatment of liver cancer has gradually started the process of precision and individualization. Actually, multidisciplinary, multimodal, and polymorphic treatments will be the most suitable pattern for liver cancer in the future, among which combination of interventional therapy with targeted, immunological treatments and information technology(IT) tools may bring a revolutionary breakthrough in liver cancer treatment.

关键词： liver cancer history interventional therapy embolization ablation multi-modal individualized treatment

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Integrative multi-omics and drug-response characterization of patient-derived prostate cancer primary cells

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3013-3028页

作者： Ziruoyu Wang Yanan Li Wensi Zhao Shuai Jiang Yuqi Huang Jun Hou Xuelu Zhang Zhaoyu Zhai Chen Yang Jiaqi Wang Jiying Zhu Jianbo Pan Wei Jiang Zengxia Li Mingliang Ye Minjia Tan Haowen Jiang Yongjun Dang Key Laboratory of Metabolism and Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesShanghai Medical CollegeFudan University200032ShanghaiChina CAS Key Lab of Separation Sciences for Analytical Chemistry National Chromatographic Research and Analysis CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences116023DalianChina The Chemical Proteomics Center and State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences201203ShanghaiChina University of Chinese Academy of Sciences 100049BeijingChina Department of Urology Zhongshan HospitalFudan University200032ShanghaiChina Department of Urology Zhongshan Hospital Wusong BranchFudan University200032ShanghaiChina Center for Novel Target and therapeutic intervention Chongqing Medical University400016ChongqingChina Department of Urology Huashan HospitalFudan University200040ShanghaiChina

Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for ***,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical *** multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in *** the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary *** further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug ***,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft *** integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.

关键词： drug PC3 diagnosis operative

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The blooming intersection of transcatheter hepatic artery chemoembolization and nanomedicine

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Chinese Chemical Letters 2020年第6期31卷 1375-1381,F0003页

作者： Hu Chen Hongwei Cheng Wenying Wu Dengfeng Li Jingsong Mao Chengchao Chu Gang Liu State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361102China Department of Radiology Xiang'an Hospital of Xiamen UniversityXiamen 361102China Department of Radiological intervention The First Hospital of China Medical UniversityShenyang 1W001China

Transcatheter hepatic artery chemoembolization(TACE)is a universal treatment for patients with hepatocellular carcinoma(HCC)that inhibits tumor growth by cutting off the blood supply and provides chemotherapeutics locally to the *** strategy of combining TACE formulation with image-guided ablation holds tremendous potential,but patient tolerance and undesired toxicity/immunosuppression remains a *** application of nanotechnology in TACE opens new doors for the treatment of ***,nanomaterials or nano-drugs dispersed in the TACE formulation can effectively improve the delivery efficiency of drugs by achieving both controlled and continuous *** addition,the utilization of multifunctional nanoparticles can provide guidance and monitoring for various advanced imaging methods for TACE treatment,and can realize the combination therapy of thermal ablation,microwave ablation,in situ radiotherapy,and other therapies,greatly expanding the therapeutic strategies available for HCC ***,the current exploration of nanotechnology in TACE of HCC is briefly summarized and the challenges of TACE with nanoformulations for clinical translation are comprehensively discussed.

关键词： Transcatheter hepatic artery chemoembolization Hepatocellular carcinoma Nanomedicine Theranostics Combination therapy

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Bioactive hydrogels for bone regeneration

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Bioactive Materials 2018年第4期3卷 401-417页

作者： Xin Bai Mingzhu Gao Sahla Syed Jerry Zhuang Xiaoyang Xu Xue-Qing Zhang Engineering Research Center of Cell&therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong University800 Dongchuan RoadShanghai200240P.R.China Department of Chemical and Materials Engineering New Jersey Institute of TechnologyNewarkNJ07102USA

Bone self-healing is limited and generally requires external intervention to augment bone repair and *** traditional methods for repairing bone defects such as autografts,allografts,and xenografts have been widely used,they all have corresponding disadvantages,thus limiting their clinical *** the development of a variety of biomaterials,including metal implants,calcium phosphate cements(CPC),hydroxyapatite,etc.,the desired therapeutic effect is not fully ***,polymeric scaffolds,particularly hydrogels,are of interest and their unique configurations and tunable physicochemical properties have been extensively *** review will focus on the applications of various cutting-edge bioactive hydrogels systems in bone regeneration,as well as their advantages and *** will examine the composition and defects of the bone,discuss the current biomaterials for bone regeneration,and classify recently developed polymeric materials for hydrogel *** will also elaborate on the properties of desirable hydrogels as well as the fabrication techniques and different delivery ***,the existing challenges,considerations,and the future prospective of hydrogels in bone regeneration will be outlined.

关键词： Bone regeneration Hydrogel Biomaterials Tissue engineering

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Hepatoprotective effects of baicalein against CCl 4-induced acute liver injury in mice

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World Journal of Gastroenterology 2012年第45期18卷 6605-6613页

作者： Hai-Li Huang Ya-Jing Wang Qing-Yu Zhang Bin Liu Fang-Yuan Wang Jing-Jing Li Run-Zhi Zhu Laboratory of Regenerative Medicine Department of Hepatobiliary SurgeryAffiliated Hospital of Guangdong Medical College Jiangsu Key Laboratory of Carcinogenesis and intervention State Key Laboratory of Natural MedicinesChina Pharmaceutical University Central Research Laboratory International Peace Maternity and Child Health HospitalShanghai Jiaotong University School of Medicine Laboratory of Regeneromics School of PharmacyShanghai Jiaotong University

AIM:To investigate the hepatoprotective effect of baicalein against carbon tetrachloride(CCl 4)-induced liver damage in ***:Mice were orally administered with baicalein after CCl 4 injection,and therapeutic baicalein was given twice a day for 4 *** anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase *** cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte *** interleukin(IL)-6,IL-1β and tumor necrosis factor-α(TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6,TNF-α,transforming growth factor-α(TGF-α),hepatocyte growth factor(HGF) and epidermal growth factor(EGF) genes expression were determined by quantitative real-time polymerase chain ***:CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated *** data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl 4 treatment in baicalein administration groups,but at 24,48 and 72 h,the expression of IL-6 and TNF-α was kept at lower levels compared with the *** expression of TGF-α,HGF and EGF was enhanced dramatically in baicalein administration group at 12,24,48 and 72 ***,we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase,which indicated that baicalein could facilitate the initiating events in liver ***:Baicalein may be a therapeutic candidate for acute liver *** accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.

关键词： Baicalein Carbon tetrachloride Liver injury Liver regeneration Hepatocyte proliferation

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