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Follow up of infection of chacma baboons with inoculum containing a and non-a genotypes of hepatitis B virus

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World Journal of Gastroenterology 2003年第4期9卷 731-735页

作者： Marina Baptista Anna Kramvis Saffie Jammeh Jocelyn Naicker Jacqueline S. Galpin Michael C. Kew University molecular hepatology Research Unit Department of MedicineUniversity of the WitwatersrandJohannesburgSouth Africa School of Statistics and Actuarial Sciences University of the WitwatersrandJohannesburgSouth Africa University molecular hepatology Research Unit Department of Medicine University of the Witwatersrand JohannesburgSouth Africa

AIM: To determine whether one genotype (A or non-A genotypes of HBV) predominated over the other during the course of HBV ***: Four baboons were inoculated with HBV. DNA was extracted from serum obtained at monthly intervals postinoculation for 52 weeks and HBV DNA was amplified using primers specific for the core region containing an insert characteristic of genotype A (nt 2 354-2 359, numbering from the EcoRI site). The amplicons were cloned into PCRScriptTM and a minimum of 15 clones per time point were sequenced in both ***: Both genotypes persisted for the entire followup period of 52 weeks. Genotype non-A predominated in two baboons and genotype A in one baboon. Neither genotype predominated in the fourth baboon, as shown at a 5 % level of ***: No conclusions concerning the dominance of either genotype or the natural progression or replication rates of HBV could be drawn because the pattern of the genotypes found may have been caused by sampling fluctuations at the time of DNA extraction and cloning as a result of the very low viral loads in the baboon sera.

关键词： Animals Base Sequence DNA Primers DNA, Viral Disease Models, Animal Genotype Hepatitis B Hepatitis B virus Papio Polymerase Chain Reaction Research Support, Non-U.S. Gov't

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2697-2715页

作者： Ze Dai Kai-Li Deng Xiao-Mei Wang Dong-Xue Yang Chun-Lan Tang Yu-Ping Zhou Department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Institute of Digestive Disease of Ningbo University Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and hepatology Ningbo Key LaboratoryNingbo 315020Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)has a high incidence and *** studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of *** To investigate the effect of indole-3-acetaldehyde(IAAD)on *** The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity *** apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium *** was investigated using the transwell *** blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream *** PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String *** IAAD reduced tumorigenesis in a syngeneic mouse *** CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the *** results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of *** can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 *** low concentrations(molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell prol

关键词： Indole-3-acetaldehyde Colorectal cancer Tryptophan metabolism Apoptosis Epithelial-mesenchymal transition

Low-dose tenofovir is more potent than adefovir and is effective in controlling HBV viremia in chronic HBeAg-negative hepatitis B

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World Journal of Gastroenterology 2007年第30期13卷 4096-4099页

作者： Paolo Del Poggio Maurizio Zaccanelli Maria Oggionni Silvia Colombo Carlo Jamoletti Vesna Puhalo hepatology Unit Treviglio Hospital (Bg) Italy Blood Bank (molecular Biology Section) Treviglio Hospital (Bg) Italy

AIM: To study the efficacy of tenofovir disoproxil fumarate (TDF) at low dose in a small open trial of chronic hepatitis B patients with advanced stage disease. METHODS: Eleven patients were treated with TDF 75 mg for a median period of 80 (range, 24-576) wk and then 7 cases were shifted to an adefovir 10 mg treatment group. All patients had been pre-treated with lamivudine: 5 had YMDD resistant mutants and 6 wild- type virus. When TDF was started, 4 patients had low- level viremia and 6 were PCR-negative. RESULTS: During TDF treatment, PCR remained negative in 10 patients, transaminase levels were normal and no significant viral breakthrough was observed. The drug was well tolerated in all cases. When TDF 75 mg was substituted with adefovir 10 mg, 3 out of 7 patients had a persistent viral rebound (2700-130 000 copies/mL), in whom lamivudine had to be reintroduced. CONCLUSION: Low-dose TDF monotherapy can control HBV viremia for an extended period of time without the emergence of resistance and is more potent than adefovir at the standard dosage. The use of a reduced dose of TDF could diminish the cost of therapy in low-income countries, but further studies in a larger population and in HBeAg-positive subjects are needed.

关键词： Tenofovir Chronic Hepatitis B Adefovir Nucleotide analogues Low-income countries

Cholangiocyte anion exchange and biliary bicarbonate excretion

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World Journal of Gastroenterology 2006年第22期12卷 3496-3511页

作者： Jesús M Banales Jesús Prieto Juan F Medina Laboratory of molecular Genetics Division of Gene Therapy and hepatology University of Navarra School of MedicineClinica Universitaria and CIMAPamplonaSpain

Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells （hepatocytes for the former and cholangiocytes for the latter）. These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels （CFTR in cholangiocytes and not yet determined in hepatocytes） and aquaporins （AQP8 in hepatocytes and AQP1 in cholangiocytes）, cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.

关键词： AE2 anion exchanger Bile salt-independent flow Biliary bicarbonate excretion Regulation of intracellular pH Hydroionic fluxes in cholangiocytes

Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

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Acta Pharmaceutica Sinica B 2015年第2期5卷 129-134页

作者： Courtney B.Ferrebee Paul A.Dawson Department of Pediatrics Division of Gastroenterology Hepatology and Nutrition Emory University molecular Medicine Graduate Program Wake Forest School of Medicine

The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size,and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor(FXR)and the G-protein-coupled bile acid receptor(TGR5).

关键词： Bile acids Liver Intestine Transporters Lipid metabolism Energy homeostasis

Host genetic factors affecting hepatitis B infection outcomes:Insights from genome-wide association studies

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World Journal of Gastroenterology 2018年第30期24卷 3347-3360页

作者： Izzet Mehmet Akcay Seyma Katrinli Kamil Ozdil Gizem Dinler Doganay Levent Doganay Department of molecular Biology and Genetics Istanbul Technical University Department of Gastroenterology and hepatology Umraniye Teaching and Research Hospital

The clinical outcome of hepatitis B virus(HBV) infection depends on the success or failure of the immune responses to HBV,and varies widely among individuals,ranging from asymptomatic self-limited infection,inactive carrier state,chronic hepatitis,cirrhosis,hepatocellular carcinoma,to liver failure,depending on the success or failure of immune response to ***-wide association studies(GWAS) identified key genetic factors influencing the pathogenesis of HBV-related *** this review,we discuss GWAS for persistence of HBV infection,antibody response to hepatitis B vaccine,and HBV-related advanced liver *** persistence is associated with multiple genes with diverse roles in immune *** strongest associations are found within the classical human leukocyte antigen(HLA) genes,highlighting the central role of antigen presentation in the immune response to *** variants affect both epitope binding specificities and expression levels of HLA *** other susceptibility genes regulate the magnitude of adaptive immune responses,determining immunity vs *** persistence and nonresponse to vaccine share the same risk variants,implying overlapping genetic *** the other hand,the risk variants for HBV-related advanced liver diseases are largely different,suggesting different host-virus dynamics in acute vs chronic HBV *** findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

关键词： Genome-wide association studies Hepatitis B infection Hepatocellular carcinoma Cirrhosis Antigen presentation Immune response to hepatitis B virus

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes

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World Journal of Gastroenterology 2005年第40期11卷 6295-6304页

作者： Hideaki Kato Kei Fujiwara Robert G. Gish Hiroshi Sakugawa Hiroshi Yoshizawa Fuminaka Sugauchi Etsuro Orito Ryuzo Ueda Yasuhito Tanaka Takanobu Kato Yuzo Miyakawa Masashi Mizokami Department of Internal Medicine and molecular Science hepatology and Gastroenterology First Department of Medicine Department of Epidemiology and Control of Infectious Diseases Department of Clinical molecular Informative Medicine Miyakawa Memorial Research Foundation

AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances ***： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.

关键词： Genotypes Hepatitis B virus Phylogeneticanalysis Subtypes

A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits

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Journal of Clinical and Translational hepatology 2024年第6期12卷 551-561页

作者： Kun Chen Junxiao Wang Liping Jiang Fei Zhao Ruochan Zhang Zhiyuan Wu Dongmei Wang Yuchen Jiao Hui Xie Chunfeng Qu State Key Lab of molecular Oncology Department of ImmunologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Oncology Fifth Medical Center of Chinese PLA General HospitalBeijingChina Aerospace Medical Center/Aerospace Center Hospital Peking University Aerospace Clinical CollegeBeijingChina State Key Lab of molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background and Aims:Hepatocellular carcinoma(HCC)cases with small nodules are commonly treated with radi-ofrequency ablation(RFA),but the recurrence rate remains *** study aimed to establish a blood signature for identifying HCC with metastatic traits ***:Data from HCC patients treated between 2010 and 2017 were retrospectively collected.A blood signature for meta-static HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin,cell-free DNA(cfDNA)mutations,and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA *** HCC blood signature was validated in patients prospectively enrolled ***:Of 251 HCC patients in the retrospective study,33.9% experienced recurrence within 1 year *** HCC blood signature identified from these patients included des-γ-carboxy-prothrombin≥40mAU/mL with cfDNA mutation score,where cfDNA mutations occurred in the genes of TP53,CTNNB1,and TERT *** signature effectively predicted 1-year post-RFArecurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset,and with 87% specificity and 76% sensitivity in the prospective dataset(n=32 patients).Among 14 cases in the prospective study with biopsy tissues available,positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and ***:This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

关键词： Liquid biopsy Liver dysplastic nodules Radiofrequency ablation Hepatocellular carcinoma Recurrence prediction Metastatic nodules

A case of hepatic angiomyolipoma difficult to distinguish from hepatocellular carcinoma

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World Journal of Gastroenterology 2009年第23期15卷 2930-2932页

作者： Masahiro Takahara Yasuhiro Miyake Kazuyuki Matsumoto Daisuke Kawai Eisuke Kaji Tatsuya Toyokawa Morihito Nakatsu Masaharu Ando Mamoru Hirohata Department of Internal Medicine Mitoyo General Hospital Kagawa 769-1695 Japan Department of molecular hepatology and Department of Gastroenterology & hepatology University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama 700-8558 Japan

We report a case of hepatic angiomyolipoma with uncommon clinical features. A 56-year-old man presented with a hepatic tumor in the caudate lobe. The tumor was hypoechoic on ultrasonography, showed early-phase hyperattenuation on enhanced computed tomography and did not absorb iron on superparamagnetic iron oxide-enhanced magnetic resonance imaging. Hepatocellular carcinoma was highly suspected, and the patient underwent hepatic resection. Histologically, the tumor was mainly composed of smooth muscle cells and contained small amounts of adipose cells and blood vessels. On immunohistochemical staining, the smooth muscle cells were positive for a melanocytic cell-specific monoclonal antibody. In cases with uncommon features of angiomyolipoma, it is quite difficult to distinguish angiomyolipoma from hepatocellular carcinoma.

关键词： Adipose cell Hepatic angiomyolipoma Hepatocellular carcinoma HMB-45 Smooth muscle cell