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Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

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Oncology Research 2024年第4期32卷 691-702页

作者： JIJIE xiao hong xiao YUJUN CAI JIANWEI liAO JUE liu lin YAO SHAOlin li department of Radiology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai510900China department of Ultrasound The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou528405China PCFM Lab of Ministry of Education School of Materials Science and EngineeringGuangzhou510275China

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient *** has shown great potential in the treatment of ***,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma *** dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor ***,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of *** laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by ***,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor ***,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

关键词： Immunotherapy Osteosarcoma Nanodrug Photodynamic therapy CD47

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in china

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World Journal of Pediatrics 2024年第5期20卷 506-516页

作者： li-Wen Tan Jun-li Wan Chun-Hua Zhu hong Xu Zheng-Kun Xia li-zhi Chen xiao-Chuan Wu Fang wang xiao-Rong liu Cheng-Guang Zhao xiao-Zhong li Jian-Hua Mao xiao-Wen wang Wen-Yan Huang Yu-hong li Jian-Jiang Zhang Shi-Pin Feng Jun Yang Jiao-Jiao liu Chun-lin Gao li-Ping Rong Lan-Jun Shuai Ke Xu He-Jia Zhang Qiu li Ai-Hua Zhang Mo wang department of Nephrology Children’s Hospital of Chongqing Medical UniversityZhongshan 2nd Rd.136Chongqing400014China Ministry of Education Key Laboratory of Child Development and Disorders National Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Pediatrics Children’s Hospital of Chongqing Medical UniversityChongqingChina department of Nephrology Children’s Hospital of Nanjing Medical University72 Guangzhou RoadNanjing210008China department of Nephrology Children’s Hospital of Fudan UniversityNational Paediatric Medical Center of ChinaShanghaiChina department of Pediatrics Jinling HospitalNanjing Medical UniversityNanjingChina department of Pediatrics Jinling HospitalThe First School of Clinical MedicineSouthern Medical UniversityNanjingChina department of Pediatrics Jinling HospitalMedical School of Nanjing UniversityNanjingChina department of Pediatric Nephrology and Rheumatology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina department of Pediatrics The Second Xiangya Hospital of Central South UniversityChangshaChina department of Pediatrics Peking University First HospitalBeijingChina department of Nephrology Beijing Children’s HospitalCapital Medical UniversityBeijing100045China National Center for Children’s Health BeijingChina department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangChina department of Nephrology and Immunology Children’s Hospital of Soochow UniversitySuzhouChina department of Nephrology Children HospitalZhejiang University School of MedicineHangzhouChina department of Nephrology Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science&TechnologyWuhanChina department of Nephrology and Rheumatology Shanghai Children’s HospitalSchool

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal ***,there are few studies on the risk factors and predictive models for renal outcomes of AAV in *** Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected *** risk factors and predictive model of end-stage renal disease(ESRD)in AAV were *** Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 *** eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal *** on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive *** Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(Pline,the predictive model had higher accuracy(0.86 versus 0.58,P2)in external *** Renal involvement is the most common manifestation of pediatric AAV in china,of which more than half deteriorates into *** predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

关键词： Antineutrophil cytoplasmic antibody End-stage renal disease Glomerulonephritis Pediatric nephrology Vasculitis

Amplified circularly polarized luminescence of chiral metal-organic frameworks via post-synthetic installing pillars

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Chinese Chemical Letters 2024年第10期35卷 485-489页

作者： Xue-zhi wang Yi-Tong liu Chuang-Wei Zhou Bei wang Dong Luo Mo Xie Meng-Ying sun yong-liang Huang jie Luo Yan Wu Shuixing Zhang xiao-Ping Zhou Dan li department of Radiology The First Affiliated HospitalJinan UniversityGuangzhou 510632China College of Chemistry and Materials Science and Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and ApplicationsJinanUniversityGuangzhou510632China department of Medicinal Chemistry Shantou University Medical CollegeShantou 515041China department of Anesthesiology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 50080China

Post-synthetic installation strategy is an effective approach to improve the functions of metal-organic frameworks(MOFs).Herein,a pair of chiral MOFs is successfully constructed through solvothermal subcomponent self-assembly and exhibit circularly polarized luminescence(CPL).These MOFs contain coordinatively unsaturated Zn sites and channels,which allow the installation of pyridyl-terminated pillars into the original *** a post-synthetic installation process reinforces the MOFs'rigidity and increases the photoluminescence quantum yields(PLQYs).Furthermore,the luminescence dissymmetry factors(glum)of these post-modified MOFs are amplified after installing the *** work provides an appealing strategy for boosting the CPL performance of chiral MOFs.

关键词： Chiral metal-organic frameworks Circularlypolarized luminescence Post-synthetic installation Pyridyl-terminated pillars Chirality transfer

Clinical manifestation,lifestyle,and treatment patterns of chronic erosive gastritis:A multicenter real-world study in china

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World Journal of Gastroenterology 2024年第9期30卷 1108-1120页

作者： Ying-Yun Yang Ke-Min li Gui-Fang Xu Cheng-Dang wang Hua Xiong xiao-Zhong wang Chun-Hui wang Bing-yong Zhang Hai-Xing Jiang Jing sun Yan Xu li-Juan Zhang Hao-Xuan Zheng Xiang-Bin Xing liang-Jing wang Xiu-li Zuo Shi-gang Ding Rong lin Chun-xiao Chen Xing-Wei wang Jing-Nan li department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100730China department of Gastroenterology Nanjing Drum Tower HospitalNanjing 21000Jiangsu ProvinceChina department of Gastroenterology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005Fujian ProvinceChina department of Gastroenterology Renji HospitalShanghai 200127China department of Gastroenterology Union Hospital of Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina department of Gastroenterology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina department of Gastroenterology and Hepatology The People’s Hospital of Zhengzhou UniversityThe Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina department of Gastroenterology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Ruijin hospital Shanghai Jiaotong university School of Medicine Shanghai Jiao Tong UnivesrityRuijin HospitalSchool MedicineShanghai 200025China department of Gastroenterology and Hepatology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina department of Gastroenterology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina department of Gastroenterology Nanfang HospitalGuangzhou 510080Guangdong ProvinceChina department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080Guangdong ProvinceChina department of Gastroenterology The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Gastroenterology Shandong University Qilu HospitalJinan 250012Shandong ProvinceChina department of Gastroenterology Peking University Third HospitalBeijing 100191China department of Gastroenterology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022Hubei Pr

BACKGROUND Although chronic erosive gastritis(CEG)is common,its clinical characteristics have not been fully *** lack of consensus regarding its treatment has resulted in varied treatment *** To explore the clinical characteristics,treatment patterns,and short-term outcomes in CEG patients in *** We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and *** and treating physicians completed a questionnaire regarding history,endoscopic findings,and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of *** Three thousand five hundred sixty-three patients from 42 centers across 24 cities in china were *** pain(68.0%),abdominal distension(62.6%),and postprandial fullness(47.5%)were the most common presenting *** was classified as chronic non-atrophic in 69.9%of *** those with erosive lesions,72.1%of patients had lesions in the antrum,51.0%had multiple lesions,and 67.3%had superficial flat *** patients with epigastric pain,the combination of a mucosal protective agent(MPA)and proton pump inhibitor was more *** those with postprandial fullness,acid regurgitation,early satiety,or nausea,a MPA appeared more *** CEG is a multifactorial disease which is common in Asian patients and has non-specific *** may play a major role in its detection and *** should be individualized based on symptom profile.

关键词： Chronic erosive gastritis Symptom Endoscopic findings Treatment pattern Real-world

Distribution of per-and polyfluoroalkyl substances in blood,serum,and urine of patients with liver cancer and associations with liver function biomarkers

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Journal of Environmental Sciences 2024年第5期139卷 418-427页

作者： Cao Dai lin Peng Yanjie li Zhendong li Da Chen Fei wang Nan lin department of Hepatobiliary Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China School of Environment Guangdong Key Laboratory of Environmental Pollution and HealthJinan UniversityGuangzhou 510632China State Key Laboratory of Environmental and Biological Analysis Department of ChemistryHong Kong Baptist UniversityHong Kong 999077China South china Institute of Environmental Sciences MEEGuangzhou 510655China

Studies have shown that per-and polyfluoroalkyl substances(PFASs)may be hepatotoxic in animals or ***,data on clinical epidemiology are very *** this study,21PFASs were determined in patients with liver diseases,with the highest median concentrations detected in the serum sample(26.7 ng/mL),followed by blood(10.7 ng/mL)and urine(5.02 ng/mL).Higher total PFAS concentrations were found in hepatocellular carcinoma(HCC)patients compared to non-HCC patients,with significant discrepancies in serum and blood ***,significant correlations were also found among PFAS concentrations and age,gender,body mass index(BMI),and liver function biomarkers *** example,PFAS concentrations are significantly higher in males than in females;Several serum PFASs concentrations increase with age and BMI,while the serum perfluorohexane sulfonic acid(PFHxS)concentrations are negatively correlated with *** addition,multiple regression models adjusted for age,gender and BMI found that increased serum perfluorobutane sulfonic acid(PFBS),perfluoroheptane sulfonic acid(PFHpS)and perfluorohexylphosphonic acid(PFHxPA)conentrations are correlated with elevated alkaline phosphatase(ALP),aspartate aminotransferase(AST),and alpha-fetoprotein(AFP)(plinical hepatotoxicity of PFAS.

关键词： Per-and polyfluoroalkyl substances(PFASs) liver cancer Serum Blood Urine liver function biomarkers

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science china(life Sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao lin-lin liu Jian sun lian Jin Hai-Bing Xie Jian-Bo li Hui Xu Dong-Dong Wu xiao-lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie sun liang-Hu Qu Jie He Zhao-li Chen Rong liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third affiliated hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

Biomolecular condensates and disease pathogenesis

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Science china(life Sciences) 2024年第9期67卷 1792-1832页

作者： Ke Ruan Ge Bai Yanshan Fang Dan li Tingting li Xingguo liu Boxun Lu Qing Lu Zhou Songyang Shuguo sun Zheng wang Xin Zhang Wen Zhou hong Zhang The first affiliated hospital&School of life Sciences Ministry of Education Key Laboratory for Membrane-less Organelles&Cellular DynamicsHefei National Research Center for Interdisciplinary Sciences at the MicroscaleCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Nanhu Brain-computer Interface Institute Hangzhou 311100China department of Neurology of Second affiliated hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou 310058China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China university of Chinese Academy of Sciences Beijing 100049China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Joint School of life Sciences Guangzhou Medical UniversityGuangzhou 510000China Neurology department at Huashan hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200433 China Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of EducationBio-X InstitutesShanghai Jiao Tong UniversityShanghai 200030China State Key Laboratory of Biocontrol MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging ResearchSchool of Life SciencesSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510275China department of Human Anatomy Hist

Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific *** of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological ***,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase *** then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological ***,we describe the emerging discovery of chemical modulators of phase separation.

关键词： liquid-liquid phase separation biomolecular condensate membraneless organelle

Protective mechanism of L-arginine against liver ischemic-reperfusion injury in rats

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Hepatobiliary & Pancreatic Diseases International 2003年第4期2卷 549-552页

作者： Shao-Qiang li li-Jian liang the department of Hepatobiliary Surgery, first affiliated hospital, sun yat-sen university, guangzhou 510080, china department of Hepatobiliary Surgery First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China. lesq@***

OBJECTIVE: To investigate the protective effect of L-arginine (L-arg) against liver ischemic-reperfusion (I/R) injury in rat model and its possible mechanism. METHODS: Male Sprague-Dawley rats were randomized into sham group: hepatoduodenal ligament mobilized, but not clamped; control group: hepatic ischemia only; Arg group: 5 minutes before hepatic ischemia, L-arg (200 mg/kg) injected via the dorsal penis vein; Arg+L group: 10 and 5 minutes before hepatic ischemia, L-NAME (30 mg/kg) and L-arg (200 mg/kg) injected via the dorsal penis vein, respectively; and Fink group: 5 minutes before, hepatic ischemia, ZVAD-fmk (15 mg/kg) injected via the dorsal penis vein. The liver was subjected to ischemia for 40 minutes by Pringle's maneuver, and reperfusion was initiated hy removing clamp. The 7-day survival rate, alanine transaminase (ALT) level, caspase-3 activity and apoptotic hepatocyte count were compared among these groups. RESULTS: After 40 minutes of ischemia and 6 hours of reperfusion, the 7-day survival rate of the Arg group was significantly higher than that of the control and Arg+L groups (Plightly higher than those in the sham and Fmk groups, but there was no statistical significance. CONCLUSIONS: L-arg could ameliorate liver I/R injury and the possible protective mechanism is inhibition of hepatocyte apoptosis via inhibition of caspase-3 activity by nitric oxide synthesis.

关键词： liver ischemia nitirc oxide caspase-3 rat

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