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Comprehensive review of hepatotoxicity associated with traditional Indian Ayurvedic herbs

World Journal of Hepatology 2020年第9期12卷 574-595页

作者： Cyriac Abby Philips Rizwan Ahamed Sasidharan Rajesh Tom George Meera Mohanan Philip Augustine the liver unit and monarch liver lab Cochin Gastroenterology GroupErnakulam Medical CenterKochi 682028KeralaIndia Gastroenterology and Advanced GI Endoscopy Cochin Gastroenterology GroupErnakulam Medical CenterKochi 682028KeralaIndia Division of Hepatobiliary Interventional Radiology Cochin Gastroenterology GroupErnakulam Medical CenterKochi 682028KeralaIndia Anesthesia and Critical Care Cochin Gastroenterology GroupErnakulam Medical CenterKochi 682028KeralaIndia

With growing antipathy toward conventional prescription drugs due to the fear of adverse events,the general and patient populations have been increasingly using complementary and alternative medications(CAMs)for managing acute and chronic *** general misconception is that natural herbal-based preparations are devoid of toxicity,and hence short-and long-term use remain justified among people as well as the CAM practitioners who prescribe these *** this regard,Ayurvedic herbal medications have become one of the most utilized in the East,specifically the Indian sub-continent,with increasing use in the *** well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic *** stems from direct effects or from indirect effects through herbal metabolites,unknown herb-herb and herbdrug interactions,adulteration of Ayurvedic drugs with other prescription medicines,and contamination due to poor manufacturing *** this exhaustive review,we present details on their hepatotoxic potential,discuss the mechanisms,clinical presentation,liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients,to support early identification and treatment of those who present with CAM-induced liver injury.

关键词： Ayurveda Complementary and alternative medicines Drug induced liver injury Herb induced liver injury Chronic liver disease AYUSH system

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Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis

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World Journal of Gastroenterology 2020年第45期26卷 7131-7152页

作者： Amit Kumar Ram Balasubramaniyan Vairappan BH Srinivas liver Diseases Research lab Department of BiochemistryJawaharlal Institute of Postgraduate Medical Education and Research(JIPMER)Dhanvantari NagarPuducherry 605006India Department of Pathology Jawaharlal Institute of Postgraduate Medical Education and Research(JIPMER)Dhanvantari NagarPuducherry 605006India

BACKGROUND Altered tight junction(TJ)proteins are correlated with carcinogenesis and tumor *** is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties;however,its anticancer effects and molecular mechanism in hepatocellular carcinoma(HCC)remains *** To investigate the effect of nimbolide on TJ proteins,cell cycle progression,and hepatic inflammation in a mouse model of *** HCC was induced in male Swiss albino mice(CD-1 strain)by a single intraperitoneal injection of 100 mg/kg diethylnitrosamine(DEN)followed by 80 ppm N-nitrosomorpholine(NMOR)in drinking water for 28 *** 28 wk,nimbolide(6 mg/kg)was given orally for four consecutive weeks in DEN/NMOR induced HCC *** the end of the 32nd week,all the mice were sacrificed and blood and liver samples were collected for various *** examinations of hepatic nodules were *** histology and HCC tumor markers such as alpha-fetoprotein(AFP)and glypican-3 were *** of TJ proteins,cell proliferation,and cell cycle markers,inflammatory markers,and oxidative stress markers were *** silico analysis was performed to confirm the binding and modulatory effect of nimbolide on zonula occludens 1(ZO-1),nuclear factor of kappa light polypeptide gene enhancer in B-cells(NF-κB),and tumor necrosis factor alpha(TNF-α).RESULTS We found nimbolide treatment at a concentration of 6 mg/kg to HCC mice reduced hepatic tumor size by 52.08%and tumor volume(P<0.01),and delayed tumor growth in HCC mice with a concomitant reduction in tumor markers such as AFP levels(P<0.01)and glypican-3 expression(P<0.05).Furthermore,nimbolide treatment increased tight junction proteins such as ZO-1 and occludin expression(P<0.05,respectively)and reduced ZO-1 associated nucleic acid binding protein expression(P<0.001)in HCC mice *** treatment to HCC mice also inhibited cell proliferation and suppressed cell cycle progression

关键词： Hepatocellular carcinoma Nimbolide Tight junction Inflammation Oxidative stress Zonula occludens 1 associated nucleic acid binding protein

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A novel TICT-based near-infrared fluorescent probe for light-up sensing and imaging of human serum albumin in real samples

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Chinese Chemical Letters 2023年第2期34卷 425-428页

作者： Yufan Fan Fangyuan Wang Fanbin Hou Lai Wei Guanghao Zhu Dongfang Zhao Qing Hu Tao Lei Ling Yang Ping Wang Guangbo Ge Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Key lab of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Putuo Hospital Shanghai University of Traditional Chinese MedicineShanghai 200062China Key laboratory of liver and Kidney Diseases(Ministry of Education) Institute of Liver DiseasesShuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201204China

Human serum albumin(HSA) has emerged as a pivotal biomarker and prognostic indicator for various human diseases. Real-time sensing and visual tracking of HSA in plasma or other biological systems will immensely facilitate the basic researchers and clinicians to better understand HSA-associated biological processes. Herein, a novel near-infrared(NIR) fluorescent probe(7-HTCF) was rationally constructed for light-up sensing and in-situ imaging of HSA in real samples, based on the principle of twisted intramolecular charge transfer(TICT). Under physiological conditions, 7-HTCF could be efficiently trapped by HSA to form a stable complex via binding on a non-drug binding site, while the complex emitted strong fluoresce signals around 670 nm. Further investigations demonstrated that 7-HTCF displayed a great combination of excellent selectivity and good chemical stability, as well as rapid fluorescent response and ultra-high sensitivity for HSA detection. Particularly, the newly developed light-up probe has been successfully utilized for quantitative detection of HSA in diluted plasma samples, while its readouts are hardly affected by the addition of therapeutic agents and herbal medicines. 7-HTCF is also successfully used for in-situ imaging of the reabsorbed HSA in living renal cells, while this dye exhibits good cell permeability and high resolution for in-situ imaging in living cells. Collectively, a novel TICT-based near-infrared fluorescent probe was devised for highly selective and ultra-sensitive sensing of HSA in plasma samples or imaging HSA in living cells, which offered a practical tool for clinical tests and for exploring HSA-associated biological processes.

关键词： Human serum albumin Near-infrared probe High-throughput detection Confocal imaging

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New real-time-PCR method to identify single point mutations in hepatitis C virus

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World Journal of Gastroenterology 2016年第43期22卷 9604-9612页

作者： Qian Chen Irene Belmonte Maria Buti Leonardo Nieto Damir Garcia-Cehic Josep Gregori Celia Perales Laura Ordeig Meritxell Llorens Maria Eugenia Soria Rafael Esteban Juan Ignacio Esteban Francisco Rodriguez-Frias Josep Quer liver unit Internal Medicine Lab. Malalties Hepàtiques Vall d’Hebron Institut Recerca-Hospital Universitari Vall d’ Hebron08035 Barcelona Spain Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos Ⅲ28029 madrid Spain liver Pathology unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Autonomous University of Barcelona 08035 Bareelona Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas del Instituto de Salud Carlos Ⅲ 28029 Madrid Spain Universitat Autònoma de Barcelona 08193 Bareelona Spain

AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This

关键词： Hepatitis C virus Resistance-associated amino acid substitutions Low-cost test Single-point mutations Q80K

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Differential gene expression between asymptomatic HBV carriers and normal adults

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Hepatobiliary & Pancreatic Diseases International 2009年第4期8卷 383-388页

作者： Tang, Cui-Lan Chen, Zhi Zhejiang Univ Sch Med Affiliated Hosp 1 State Key Lab Diag & Treatment Infect Dis Hangzhou 310003 Zhejiang Peoples R China Xinhua Hosp Zhejiang Prov Dept Liver Dis Hangzhou 310005 Zhejiang Peoples R China

BACKGROUND: There are more than 100 million wa symptomatic HBV carriers (ASCs) in China and they are at a high risk of developing liver disease, which creates a serious health problem. But more than 90% of normal adults clear virus from primary HBV infection, so the difference of gene expression between ASCs and normal adults determines the differential outcomes. To identify differentially expressed genes in ASCs compared to normal adults, we used suppression subtractive hybridization to compare gene expression. METHODS: cDNA subtracted libraries were constructed by suppression subtracted hybridization from peripheral blood monocytes of ASCs and normal adults, the subtracted clones were prescreened by dot blot hybridization, and the levels of genes of interest were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: One hundred and two and 96 positive clones were acquired from the A-N and N-A libraries, respectively, and 14 and 11 clones were identified by dot blot hybridization in the A-N and N-A libraries. Two genes were confirmed as differentially expressed between a set of ASC and normal adult samples by real-time RT-PCR. CONCLUSIONS: Differentially expressed genes in peripheral blood mononuclear cells between ASCs and normal adults were isolated by suppression subtractive hybridization, and included some new genes. Of the upregulated genes in ASCs, checkpoint suppressor I is associated with DNA damage-induced cell cycle arrest. Perforin I is associated with inflammation. The information about such alterations in gene expression could be useful for elucidating the mechanisms of ASC pathogenesis.

关键词： hepatitis B virus asymptomatic HBV carriers suppression subtractive hybridization dot blot hybridization reverse transcriptase-polymerase chain reaction

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Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

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World Journal of Gastroenterology 2015年第7期21卷 2058-2066页

作者： Qin He Jin-Ke Li Fang Li Ru-Gui Li Guo-Qing Zhan Gang Li Wei-Xing Du Hua-Bing Tan Department of Infectious Diseases and lab of liver Disease Renmin Hospital Hubei University of Medicine

AIM:To explore the mechanism of action of gypenosides(GPs)on type 2 diabetes mellitus and non-alcoholic fatty liver disease(T2DM-NAFLD)in ***:Sixty rats were randomly divided into a healthy group,an untreated disease model group andGP-treatment *** study involved the evaluation of biochemical parameters,including serum aspartate transaminase(AST),alanine transferase(ALT),blood glucose(BG),triglycerides(TG)and total cholesterol(TC).Additionally,the protective effect of the treatments were confirmed histopathologically and the expression of TNF-αand NF-κB in the rat liver was analyzed using *** expression of proliferatoractivated receptor gamma(PPARγ)and cytochrome P450(CYP450)1A1 m RNA was determined by quantitative ***:GP treatments at oral doses of 200,400,and800 mg/kg per day significantly decreased the levels of serum AST and ALT(Pliver fats and reversed the histopathological changes in a dosedependent ***:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-αand NF-κB proteins,and PPARγand CYP4501A1 m RNAs.

关键词： Gypenosides Type 2 diabetes mellitus Non-alcoholic

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Highly uniform ultrasound-sensitive nanospheres produced by a pH-induced micelle-to-vesicle transition for tumor-targeted drug delivery

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Nano Research 2018年第7期11卷 3710-3721页

作者： Yiru Wang Tinghui Yin Zhenwei Su Chen Qiu Yong Wang Rongqin Zheng Meiwan Chen Xintao Shuai Guangdong Provincial Key lab of liver Disease and Department of Medical Ultrasonics The Third Affiliated Hospital of Sun Yat-sen University Guangzhou 510630 China PCFM lab of Ministry of Education School of Materials Sdence and Engineering Sun Yat-sen University Guangzhou 510275 China State Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao Macao 999078 China

Although gas-filled microbubbles with high echogenicity are widely applied in clinical ultrasonography, the micron scale particle size impedes their use in the treatment of solid tumors, which are accessible to objects less than several hundred nanometers. We herein propose an unusual approach involving a pH-induced core-shell micelle-to-vesicle transition to prepare ultrasound-sensitive polymeric nanospheres （polymersomes in structure） possessing multiple features, including nanosize, monodispersity, and incorporation of a phase- transitional imaging agent into the aqueous lumen. These features are not achievable via the conventional double-emulsion method for polymersome preparation. The nanospheres were constructed based on a novel triblock copolymer with dual pH sensitivity. The liquid-to-gas phase transition of the imaging agent induced by external low-frequency ultrasound may destroy the nanospheres for a rapid drug release, with simultaneous tissue-penetrating drug delivery inside a tumor. These effects may provide new opportunities for the development of an effective cancer therapy with few adverse effects.

关键词： micelle polymersome morphological transition ultrasound-sensitive tumor-penetratingdelivery

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Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis

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Chinese Medical Journal 2011年第18期124卷 2813-2817页

作者： WEN Hao DONG Jia-hong ZHANG Jin-hui ZHAO Jin-ming SHAO Ying-mei DUAN Wei-dong LIANG Yu-rong JI Xue-wen TAI Qin-wen Tuerganali Aji LI Tao State Key lab Breeding Base of Xinjiang Major Disease Research and Department of liver and Laparoscopic Surgery First Affiliated Hospital of Xinjiang Medical University Xinjiang Organ Transplantation Research Institute Urumqi Xinjiang 830054 China Department of Hepatobiliary Surgery General Hospital of People'sLiberation Army Beijing 100853 China

Background For patients with end-stage hepatic alveolar echinococcosis （AE）, in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure. Methods We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments （II and III） of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases （such as to the lung or brain） could be found. As the first step of treatment, X-ray guided percutaneous transhepatic cholangiodrainage （PTCD） was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 umol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the-left liver were re-implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto-caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems. Results During a 60-day following-up after ope

关键词： liver autotransplantation alveolar echinococcosis ex vivo liver resection liposomal albendazole

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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa Roade Mar Riveiro-Barciela Adriana Palom Francisco Rodríguez-Frías Marta Bes Ariadna Rando María Teresa Salcedo Rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda Rafael Esteban María Buti liver unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain liver Pathology lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de Recerca(VHIR) Liver Diseases GroupBarcelonaSpain Transfusion Safety laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their *** aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their ***-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative ***,analytical,and virological data were collected,and a liver biopsy was performed if *** were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap ***:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray ***-nine(25.9%)individuals re-quired a liver *** HBV DNA hazard ratio(HR)6.0,pliver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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Molecular epidemiology and putative origin of hepatitis C virus in random volunteers from Argentina

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World Journal of Gastroenterology 2013年第35期19卷 5813-5827页

作者： Noemí del Pino José Raúl Oubia Francisco Rodríguez-Frías Juan Ignacio Esteban María Buti Teresa Otero Josep Gregori Damir García-Cehic Silvia Camos María Cubero Rosario Casillas Jaume Guàrdia Rafael Esteban Josep Quer Apunlab laboratories Institute of Medical Microbiology and Parasitology (IMPAM) UBA-CONICET Department of MicrobiologyParasitology and Immunology Faculty of Medicine University of Buenos Aires CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos Ⅲ and Biochemistry Department Hospital Universitari Vall d’Hebrón (HUVH) CIBERehd del Instituto de Salud Carlos Ⅲ Autonomous University of Barcelona and Liver Unit Internal Medicine Lab. Malalties Hepatiques Vall d’Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d’Hebrón (HUVH) unitat de Diagnostic Molecular HUVH liver unit Internal Medicine Lab Malalties Hepatiques VHIR-HUVH Roche Diagnostics SL CIBERehd del Instituto de Salud Carlos Ⅲ Liver Unit Internal Medicine Lab MalaltiesHepatiques VHIR-HUVH liver unit and Biochemistry Department HUVH

AIM:To study the subtype prevalence and the phylogenetic relatedness of hepatitis C virus(HCV)sequences obtained from the Argentine general population,a large cohort of individuals was ***:Healthy Argentinian volunteers(n=6251)from 12 provinces representing all geographical regions of the country were *** parents or legal guardians of individuals younger than 18 years provided informed written consent for *** corresponding written permission from all municipal authorities was obtained from each city or town where subjects were to be *** RNA reverse transcription-polymerase chain reaction products were sequenced and phylogenetically *** 5’untranslated region(5’UTR)was used for RNA detection and initial genotype *** NS5B polymerase region,encompassing nt 8262-8610,was used for ***:An unexpectedly low prevalence of HCV infection in the general population(0.32%)was *** data contrasted with previous studies that reported rates ranging from 1.5%to 2.5%,mainly performed in selected populations of blood donors or vulnerable *** latter values are in keeping with the prevalence reported by the 2007 Argentinian HCV Consensus(approximately 2%).HCV subtypes weredistributed as follows:1a(25%),1b(25%),2c(25%),3a(5%),and 2j(5%).Two isolates ascribed either to genotype 1(5%)or to genotype 3(5%)by 5’UTR phylogenetic analysis could not be *** 1a sequences comprised a highly homogeneous population and clustered with united States ***1b sequences represented a heterogeneous population,suggesting that this genotype might have been introduced from different *** subtype 2c sequences clustered close to the 2c reported from Italy and Southern ***:HCV has a low prevalence of 0.32%in the studied general population of *** pattern of HCV introduction and transmission in Argentina appears to be a consequence of multiple events and different

关键词： Hepatitis C virus NS5B subtyping Molecular epidemiology Hepatitis C virus Argentina Hepatitis C virus 5’ untranslated region

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