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Thrombotic Venous Diseases of the Liver

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Journal of Clinical and Translational Hepatology 2015年第3期3卷 189-194页

作者： Timothy P.Sabol Marco Molina george Y.wu Department of Graduate Medical Education Eastern Connecticut Health Network Manchester Memorial Hospital Manchester CT USA Department of Radiology University of Connecticut Health Center Farmington CT USA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Thrombotic venous diseases of the liver do not occur frequently,but when they do,they can present as difficult diagnostic and therapeutic *** aim of this article is to review the epidemiology,pathogenesis,diagnosis,an... 详细信息

关键词： Thrombosis Hepatic veins Portal hypertension

Update on the Development of Anti-Viral Agents Against Hepatitis C

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 9-21页

作者： Kristin L. MacArthur Robert Smolic Martina V. Smolic Catherine H. wu george Y. wu Department of Medicine Beth Israel Deaconess Medical Center Boston MA02215 Faculty of Medicine Osijek Croatia University of Connecticut Health Center Farmington CT USA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT USA

Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase Ⅲ/Ⅳ clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options.

关键词： HCV Protease Polymerase Triple therapy Drug.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han Xiaoyun Wang Chunmei Wang Xinxin Yan Wenwen Lei Ke Xu Jianjie Zhou Jianxun Qi Ruiwen Fan Guizhen wu Wen-xia Tian george F.Gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

Gene Therapy for Liver Diseases

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肝脏 2002年第S1期7卷 2-3页

作者： george wu Catherine H wu DepartmentofMedicine DivisionofGastroenterologyHepatologyUniversityofConnecticutSchoolofMedicineFarmingtonDepartmentofMedicineDivisionofGastroenterologyHepatologyUniversityofConnecticutSchoolofMedicineFarmington CT06030USACT06030USA

Drug-induced Fatty Liver Disease:Pathogenesis and Treatment

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 731-737页

作者： Tea Omanovic Kolaric Vjera Nincevic Lucija Kuna Kristina Duspara Kristina Bojanic Sonja Vukadin Nikola Raguz-Lucic george Y wu Martina Smolic University of Osijek Faculty of MedicineOsijekCroatia University of Osijek Faculty of Dental Medicine and HealthOsijekCroatia Health Center Osijek OsijekCroatia Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Metabolic dysfunction-associated fatty liver disease(commonly known as MAFLD)impacts global health in epidemic proportions,and the resulting morbidity,mortality and economic burden is *** much attention has been given to metabolic syndrome and obesity as offending factors,a growing incidence of polypharmacy,especially in the elderly,has greatly increased the risk of drug-induced liver injury(DILI)in general,and drug-induced fatty liver disease(DIFLD)in *** review focuses on the contribution of DIFLD to DILI in terms of epidemiology,pathophysiology,the most common drugs associated with DIFLD,and treatment strategies.

关键词： Metabolic dysfunction-associated fatty liver disease Drug-induced liver injury Reactive oxygen species Free fatty acids Pharmacogenetics

Hepatitis C and HIV co-infection:a review

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World Journal of Gastroenterology 2002年第4期8卷 577-579页

作者： Irena Maier george Y. wu Department of Medicine Division of Gastroenteroiogy-Hepatology University of Connecticut Health CenterFarmingtonCTUSA Department of Medicine Division of Gastroenterology-Hepatology University of Connecticut Health CenterFarmingtonCTUSA

Co-infection with hepatitis C virus and humanimmunodeficiency virus is common in certainpopulations. Among HCV(+) persons, 10 % are alsoHIV (+), and among HIV (+) persons, 25 % are alsoHCV(+). Many studies have shown that in intravenousdrug users, co-infection prevalence can be as high as90-95 %. There is increasing evidence supporting theconcept that people infected with HIV have a muchmore rapid course of their hepatitis C *** of co-infection is often challenging becausehighly active anti-retroviral therapy (HAART) therapyis frequently hepatotoxic, especially in the presence ofHCV. The purpose of this review is to describe theeffects that HIV has on hepatitis C, the effects thathepatitis C has on HIV, and the treatment options inthis challenging population.

关键词：丙型肝炎病毒 HIV 合并感染高危人群感染率

Occult HCV Infection (OCI) Diagnosis in Cirrhotic and Non-cirrhotic Naive Patients by Intra-PBMC Nested Viral RNA PCR

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Journal of Clinical and Translational Hepatology 2017年第4期5卷 319-326页

作者： Mohamed Darwish Ahmed Abd Alla Saleh Ahmed Elibiary george Y.wu Mostafa Kamel El-Awady Tropical Medicine Department Faculty of MedicineAl-Azhar UniversityCairoEgypt Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA Department of Microbial Biotechnology National Research CenterCairoEgypt

Background and Aims:Occult HCV infections(OCIs)include IgG antibody seronegative cryptogenic(COCIs),as well as seropositive secondary na(i)ve(SNOCIs)and experienced(SEOCIs)*** used peripheral-blood-mononuclear-cell(PBMC)-PCR to evaluate COCIs and SNOCIs prevalence,serum HCV spontaneous disappearance(SCSD)in na(i)ve cirrhotics and non-cirrhotics,intra-PBMC HCV-RNA strands in relation to cirrhosis density in na(i)ve non-viremia cases,and HCV-RNA seroconversion after 1 year of solitary naive intra-PBMC ***:The anti-HCV IgG antibodypositive na(i)ve-patients(n=785)were classified into viremic(n=673)and non-viremic[n=112,including non-cirrhotics(n=55)and cirrhotics(n=57)],and 62 controls without evidence of *** and post-HCV non-viremia cases(n=62+112=174)were submitted to hepatic FibroscanElastography *** subjects(n=847)were screened for intra-PBMC HCV-RNA sense and antisense strands by ***:Na(i)ve-OCI cases(4.84%)that were diagnosed by PBMC-PCR significantly raised the total numbers of HCV-infection to 714(p=0.01).The percent positivity of SNOCIs(34.82%)was significantly higher than for asymptomatic-COCIs(3.125%,p=0.0001).Comparing PBMC-PCR with single-step-reverse-transcription(SRT)-PCR for identification of SCSD in na(i)ve IgG antibody-positive nonviremia patients(n=112)revealed a decline in SCSD prevalence by PBMC-PCR(from 14.27%to 9.3%),regardless of presence of hepatic cirrhosis(p=0.03).SCSD was found to be higher by PBMC-PCR in non-cirrhotics compared to cirrhotics(p=0.0001),with an insignificant difference when using SRT-PCR(p=0.45).Intra-PBMC HCV-RNA infection was significantly more frequent in cirrhotics compared to both non-cirrhotics and controls(p<0.0005).An increased hepatic fibrosis density was recognized in intra-PBMC HCV-RNA infection with sense(p=0.0001)or antisense strand(p=0.003).HCV-RNA seroconversion was associated with intra-PBMC infection when both sense and antisense strands were dete

关键词： OCIs PBMCs Na(i)ve Cirrhosis

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing wu Wei wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia george Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

HCV Therapy Follow-up Fractionation (CTF2) by Intra-PBMC Nested RNA PCR Recognizes Early Virologic Response and Relapse

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Journal of Clinical and Translational Hepatology 2018年第2期6卷 147-154页

作者： Mohamed Darwish Ahmed Abd Alla Saleh Ahmed Elibiary Ramy Hassan Elshaboury george Y.wu Reham M.Dawood Mostafa Kamel El Awady Tropical Medicine Department Faculty of MedicineAl-Azhar UniversityCairoEgypt Department of Pharmacy Massachusetts General HospitalBostonMAUSA Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterHartfordCTUSA Department of Microbial Biotechnology National Research CenterCairoEgypt

Background and Aims:Sustained virologic response is evaluated by single-step reverse transcription(SRT)PCR as-say,which assesses hepatitis C virus(HCV)clearance from plasma but not from tissues such as peripheral blood mono-nuclear cells(PBMCs).Persistence of HCV RNA in PBMCs beyond end of treatment(EOT)is associated with *** goal was to measure intra-PBMC HCV RNA levels during oral antiviral therapy according to the HCV therapy follow-up fractionation(CTF2)***:Compen-sated chronic HCV patients(n=278 SRT-PCR positive)were scheduled to receive oral antiviral *** were followed-up by SRT and intra-PBMCs HCV RNA PCR at the end of the 2nd,6th,10th,14th,18th and 24th weeks to evaluate virus clearance from plasma and PBMCs,*** CTF2 protocol evaluated SRT and PBMC PCR status at each follow-up point for determining therapy continuation or inter-ruption to address cost ***:All patients tested negative by SRT PCR after therapy for 2 ***-cation of the CTF2 protocol revealed:a)increasing HCV clear-ance rate from 75.9%at the end of 10th week to 90.3%at the end of 24th week(p<0.00001);b)faster clearance of HCV from plasma compared to PBMCs at each point of follow-up until the 18th week(p<0.05);c)higher viral elimination rates diagnosed by PBMC HCV RNA PCR(?)compared to PBMC HCV RNA PCR(+)from the 6th to 24th week of treatment(p<0.0001);d)higher over-time increase curve of combined plasma and PBMC HCV RNA determined negativity compared to the decline in positivity curves by PBMC PCR at the 6th-18th week compared to the 24th week(p<0.01)—these results validated treatment continuation;and e)solitary evaluation of EOT sustained HCV infection and relapses by PBMC HCV RNA(p<0.001).Conclusions:Early elimination of serum and tissue(PBMC)HCV infection by oral antiviral therapy can be achieved and evaluated during a cost-effective CTF2 pro-tocol application.

关键词： CTF2 protocol HCV PBMCs PCR Cost-effectiveness