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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song harry ch.lau Xiang Zhang Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

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Gut microbiome alters functions of mutant p53 to promote tumorigenesis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 491-492页

作者： harry cheuk Hay lau Jun Yu Institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongSha TinN.T.Hong Kong

In a recent study in Nature,Kadosh et al.1 established a landmark relationship between the gut microbiome and host epigenetics in intestinal *** demonstrated the substantial plasticity of mutant p53 in WNT-driven tumo... 详细信息

关键词： tumorigenesis involvement al

Microbiota-mediated phytate metabolism activates HDAC3 to contribute intestinal homeostasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 747-748页

作者： Xiaoxing Li harry cheuk Hay lau Jun Yu Institute of Precision Medicine First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina Institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongSha TinNewTerritoriesHong Kong

In a recent study in Nature,Wu et *** a fundamental host–microbe interaction that is crucially involved in responding to dietary change thereby maintaining healthy intestinal dynamics.1 They demonstrated that HDAC3 a... 详细信息

关键词： metabolism HDAC3 homeostasis

Gut Microbiome in Colorectal Cancer:Clinical Diagnosis and Treatment

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 84-96页

作者： Yali Liu harry cheuk-Hay lau Wing Yin cheng Jun Yu Institute of Digestive Disease and The Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong Kong Special Administrative Region 999077China

Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated *** studies have shown that both genetic and environmental risk factors contribute to the development of *** metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal *** enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC,the precise mechanisms involved remain *** data have shown a direct causative role of the gut microbiome in DNA damage,inflammation,and drug resistance in CRC,suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and ***,we provide an overview of the relationship between gut microbiome and CRC,and explore relevant mechanisms of colorectal *** next highlight the potential of bacterial species as clinical biomarkers,as well as their roles in therapeutic *** limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.

关键词： Gut microbiome Colorectal cancer Diagnostic biomarker Immunotherapy chemotherapy

Uncovering novel human gut virome using ultra-deep metagenomic sequencing

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chinese Medical Journal 2022年第20期135卷 2395-2397页

作者： harry cheuk Hay lau Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health Sciencesthe Chinese University of Hong KongHong Kong SARChina

Human gastrointestinal tract harbors trillions of commensal microbes including bacteria,viruses,and fungi to form an ecological community,commonly known as the gut *** the second most dominant taxonomic kingdom in the gut(5.8%of total microbiome DNA),enteric viruses are increasingly acknowledged for their roles in shaping the overall composition of the gut microbiome and maintaining human health.[1,2]Recent advancements in metagenomic sequencing have brought breakthrough in deciphering the features and functions of the gut virome.

关键词： breakthrough harbor gut

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Measurements of Heat Treatment Effects on Bovine Cortical Bones by Nanoindentation and Compression Testing

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Journal of Biomaterials and Nanobiotechnology 2012年第1期3卷 105-113页

作者： Mei-ling lau Kin-tak lau harry Ku Debes Bahattacharyya Yan-dong Yao Centre for Advanced Composite Materials Department of Mechanical Engineering The University of Auckland Auckland New Zealand Centre of Excellence in Engineered Fibre Composites Faculty of Engineering and Surveying University of Southern Queensland Toowoomba Australia Department of Applied Biology and chemical Technology The Hong Kong Polytechnic University Hong Kong China

Heat treatment of bone is one of the reliable and simple sterilization methods to overcome the risk of rejection and disease transfer from allograft and xenograft, in particular for the prevention of human immunodeficiency virus (HIV) infection. However, the mechanical property of the micro-structural level after heat treatment is not well characterized. To address this issue, this study was carried out to compare the localized mechanical properties of micro-structural tissue with those at the global structural level. Nanoindentation technique has been well accepted as an accurate technique to measure mechanical property of small and heterogeneous specimen nondestructively, as well as the complex bio-material of micro-structural level, often with a resolution of better than 1 μm. In this study, nanoindentation was conducted to measure the localised elastic modulus and hardness values of bones at temperature of 23°C (room temperature – non-heated sample), 90°C and 150°C, respectively. All experiments were conducted at room temperature (~23°C). The elastic modulus (E) and nanoindentation hardenss (H) values in the longitudinal direction of bones heated at 150°C were recorded as 23.43 GPa and 0.73 GPa, respectively;as in transverse direction, the E and H values were 12.77 GPa and 0.54 GPa, respectively. It showed significant increases of 44% and 43% in the longitudinal direction as compared to those of the non heat-treated bones. In addition, E and H values in transverse direction also showed increases of 23% and 38%, respectively as compared to those of the non heat-treated bones. Furthermore, heat-treated bones at 90°C in longitudinal direction also appeared to have significant increases of 18% and 31% in E and H values, respectively. However, the E and H values in transverse direction increase only by 0.4% and 12.8%, respectively. In addition, compressive test is employed to measure the global stiffness (E) of the bone samples. When heated at 150°C, the bone specime

关键词： Bone Heat Treatment Nanoindentation Mechanical Properties BSE and EDX

片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

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Engineering 2024年第4期35卷 257-269页

作者： Xianyi Zeng Xiang Zhang Hao Su Hongyan Gou harry cheuk-Hay lau Xiaoxu Hu Ziheng Huang Yan Li Jun Yu Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China

Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective *** traditional chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory ***,we evaluate the effects of PTH on the evolution of NASH and its underlying *** found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid ***,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in *** the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(***),Lactobacillus plantarum,Lactococcus lactis,and Bacillus *** enriched *** prevented MCD diet-induced *** addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin *** metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated *** further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis *** conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and *** is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang Non-alcoholic steatohepatitis Gut barrier function Gut microbiota

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Carboxyl Ester Lipase Protects Against Metabolic Dysfunction-Associated Steatohepatitis by Binding to Fatty Acid Synthase

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Engineering 2024年第10期41卷 204-215页

作者： Yang Song Wei Zhong harry cheuk-Hay lau Yating Zhang Huayu Guan Mingxu Xie Suki Ha Diwen Shou Yongjian Zhou Hongzhi Xu Jun Yu Xiang Zhang Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China Shenzhen Research Institute The Chinese Unviersity of Hong KongShenzhen 518057China Department of Gastroenterology&Institute for Microbial Ecology&Xiamen Key Laboratory of Intestinal Microbiome and Human Health&Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province Zhongshan Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361004China Division of Gastroenterology and Hepatology Renji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200025China Department of Gastroenterology and Hepatology Guangzhou Digestive Disease CenterGuangzhou First People’s HospitalGuangzhou 510180China

Carboxyl ester lipase(CEL),a pivotal enzyme involved in lipid metabolism,is recurrently mutated in obese ***,we aimed to elucidate the functional significance,molecular mechanism,and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis(MASH).Hepatocyte-specific carboxyl ester lipase gene(Cel)knockout(Cel^(DHEP))and wildtype(WT)littermates were fed with cholinedeficient high-fat diet(CD-HFD)for 16 weeks,or methionine-and choline-deficient diet(MCD)for three weeks to induce *** chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of ***-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral,serotype 8(AAV8)to induce specific overexpression of CEL in the *** observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in ***^(DHEP) mice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis,inflammation,lipid peroxidation,and liver injury compared to WT littermates,accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell(NF-jB)***,Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation,whereas CEL overexpression exerted the opposite ***,CEL directly bound to fatty acid synthase(FASN),resulting in reduced FASN SUMOylation,which in turn promoted FASN degradation through the proteasome ***,inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in ***-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or *** protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo *** overexpression confers a therapeutic benefit in steatohepatitis.

关键词： Metabolic dysfunction-associated steatohepatitis Carboxyl ester lipase Fatty acid synthase De novo lipogenesis Treatment

Critical flow-storm approach to total maximum daily load (TMDL) development:an analytical conceptual model

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Frontiers of Environmental Science & Engineering 2008年第3期2卷 267-273页

作者： harry X.ZHANG Shaw L.YU ch2M HILL 15010 Conference Center DriveChantillyVA 20151–3801USA Department of Civil and Environmental Engineering Thornton HallUniversity of VirginiaCharlottesvilleVA 22904–4742USA

One of the key challenges in the total maximum daily load(TMDL)development process is how to define the critical condition for a receiving *** main concern in using a continuous simulation approach is the absence of any guarantee that the most critical condition will be captured during the selected representative hydrologic period,given the scarcity of long-term continuous *** objectives of this paper are to clearly address the critical condition in the TMDL development process and to compare continuous and event-based approaches in defining critical condition during TMDL development for a waterbody impacted by both point and nonpoint source pollution.A practical,event-based critical flow-storm(CFS)approach was developed to explicitly addresses the critical condition as a combination of a low stream flow and a storm event of a selected magnitude,both having certain frequencies of *** paper illustrated the CFS concept and provided its theoretical basis using a derived analytical conceptual *** CFS approach clearly defined a critical condition,obtained reasonable results and could be considered as an alternative method in TMDL development.

关键词： critical condition critical flow-storm(CFS)approach total maximum daily load(TMDL) conceptual model derived analytical model nonpoint source pollution