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World Journal of Gastroenterology 2024年第22期30卷 2839-2842页

作者： Chen-Xiao Huang Xiao-Dong Zhou Calvin Q Pan Ming-Hua Zheng metabolic dysfunction-associated fatty liver disease research center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Cardiovascular Medicine The Key Laboratory of Cardiovascular Diseases of WenzhouThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Division of Gastroenterology and Hepatology Department of MedicineNew York University Langone HealthNew York University Grossman School of MedicineNew YorkNY 11355United States Institute of Hepatology Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang ProvinceWenzhou 325000Zhejiang ProvinceChina

metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition *** liver enzyme-based screening methods have limitations that may missed diagnoses and treatment *** Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal ***,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early *** paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

关键词： metabolic dysfunction-associated fatty liver disease Non-alcoholic fatty liver disease Alanine aminotransferase liver enzymes Screening Noninvasive liver fibrosis scores

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

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metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong Chen Wei Yang Ligong Chen Jianping Ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China metabolic disease research center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China research center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter *** transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and *** actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of metabolic liver diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage liver disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

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World Journal of Gastroenterology 2024年第11期30卷 1556-1571页

作者： Yan-Chao Hu Xiang-Chun Ding Hui-Juan Liu Wan-Long Ma Xue-Yan Feng Li-Na Ma Department of Infectious disease General Hospital of Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Infectious disease Clinical research center of Ningxia Yinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic *** the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been *** To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC *** This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December *** were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment *** samples were collected at the onset and conclusion of the 12-wk intervention *** structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were *** Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(Pliver function indices and significantly lower levels of inflammatory factors(Pliver function,and reducing inflammatory factor levels.

关键词： Hepatitis B cirrhosis N1115 ready-to-eat lactobacillus Inflammation liver function Lachnospiraceae incertae sedis Probiotic

When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

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Science China(Life Sciences) 2024年第5期67卷 854-864页

作者： Bo Chen Guangyi Zeng Lulu Sun Changtao Jiang center of Basic Medical research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China center for Obesity and metabolic disease research School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Women’s Reproductive Health and Fertility Promotion Peking UniversityBeijing 100191China Department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and *** previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these *** tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and *** review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and *** also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host ***,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

关键词： tobacco smoking gut microbiota dysbiosis nicotine smoking cessation

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The journey towards physiology and pathology: Tracing the path of neuregulin 4

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Genes & diseases 2024年第2期11卷 687-700页

作者： Min Chen Jieying Zhu Hongyang Luo Wangjing Mu Liang Guo School of Exercise and Health and Shanghai Frontiers Science research Base of Exercise and metabolic Health Shanghai University of SportShanghai 200438China

Neuregulin 4 (Nrg4),an epidermal growth factor (EGF) family member,can bind to and activate the ErbB4 receptor tyrosine ***4 has five different isoforms by alternative splicing and performs a wide variety of ***4 is involved in a spectrum of physiological processes including neurobiogenesis,lipid metabolism,glucose metabolism,thermogenesis,and *** pathological processes,Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory *** addition,Nrg4 could ameliorate obesity,insulin resistance,and cardiovascular ***,Nrg4 improves non-alcoholic fatty liver disease (NAFLD) by promoting autophagy,improving lipid metabolism,and inhibiting cell death of ***,Nrg4 is closely related to the development of cancer,hyperthyroidism,and some other ***,elucidation of the functional role and mechanisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.

关键词： Angiogenesis Cardiovascular diseases Inflammation Insulin resistance Lipid and glucose metabolism NAFLD Neurobiogenesis Obesity

The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts

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Journal of Genetics and Genomics 2024年第7期51卷 735-748页

作者： Tongyu Zhang Yingxi Zhu Xiaochen Wang Danyang Chong Haiquan Wang Dandan Bu Mengfei Zhao Lei Fang Chaojun Li Ministry of Education Key Laboratory of Model Animals for disease Study Model Animal Research CenterMedical School of Nanjing UniversityNational Resource Center for Mutant MiceNanjingJiangsu 210093China State Key Laboratory of Reproductive Medicine and Offspring Health China International Joint Research Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthGusu SchoolNanjing Medical UniversityNanjingJiangsu 211166China

In mammals,the neonatal heart can regenerate upon injury within a short time after birth,while adults lose this *** reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal ***,we reveal that cardiac metabolic reprogramming could be regulated by altering global protein *** performing 4D label-free proteomics and lysine lactylation(Kla)omics analyses in mouse hearts at postnatal days 1,5,and 7,2297 Kla sites from 980 proteins are identified,among which 1262 Kla sites from 409 proteins are *** clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic *** expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid ***,we verify the Kla levels of several differentially modified proteins,including ACAT1,ACADL,ACADVL,PFKM,PKM,and ***,our study reports a comprehensive Kla map in the neonatal mouse heart,which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

关键词： Lactylation metabolicrep rogramming Postnatal heart regeneration Cell proliferation

Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical University Department of Hepatology Tianjin Second People's Hospital Tianjin Institute of Hepatology Department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

Non-alcoholic fatty liver degree and long-term risk of incident inflammatory bowel disease: A large-scale prospective cohort study

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中华医学杂志(英文版) 2024年第14期137卷 2023 Nov 13页

作者： Zhang Qian Liu Si Wu Jing Zhu Shengtao Wu Yongdong Wu Shanshan Zhang Shutian Department of Gastroenterology Beijing Friendship Hospital Capital Medical University National Clinical Research Center for Digestive Disease Beijing Digestive Disease Center Beijing Key Laboratory for Precancerous Lesion of Digestive Disease Beijing China

Background: Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective ***: Participants from the United Kingdom Biobank cohort (https://***/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years’ follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HRQ4vs. Q1 =1.36, 95% CI: 1.19-1.55,Ptrend fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatm

关键词： Non-alcoholic fatty liver disease Inflammatory bowel disease Ulcerative colitis Crohn’s disease Cohort study