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Update on cell therapy for stroke

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Stroke & Vascular Neurology 2017年第2期2卷 59-64页

作者： cynthia L Kenmuir Lawrence R Wechsler Department of Neurology University of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA

Ischaemic stroke remains a leading cause of death and *** stroke treatment options aim to minimise the damage from a pending stroke during the acute stroke period using intravenous thrombolytics and endovascular thrombectomy;however,there are no currently approved treatment options for reversing neurological damage once a stroke is *** studies suggest that cell therapy may be safe and effective in improving functional *** recent clinical trials have reported safety and some improvement in outcomes following cell therapy administration in ischaemic stroke,which are *** therapy may provide a promising new treatment for stroke reducing stroke-related *** investigation is needed to determine specific effects of cell therapy and to optimise cell delivery methods,cell dosing,type of cells used,timing of delivery,infarct size and location of infarct that are likely to benefit from cell therapy.

关键词： damage acute treatment

Hepatic macrophages in drug-induced liver injury

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Liver Research 2019年第3期3卷 170-175页

作者： Zhao Shan cynthia Ju Center for Life Sciences School of Life SciencesYunnan UniversityKunmingChina Department of Anesthesiology UTHealth McGovern Medical SchoolHoustonTXUSA

Drug-induced liver injury(DILI)is a major public health *** DILI,for example,acetaminophen overdose accounts for half of acute liver failure in the United ***,the most problematic type of DILI affecting drug development and health care is idiosyncratic DILI,which occurs unpredictably in a small population of patients taking the drug and the latency could be several weeks to *** knowledge on the pathogenesis of DILI suggest that hepatic macrophages play a central role in the initiation,progression and restoration stages of DILI,which make hepatic macrophages attractive as therapeutic *** macrophages consist of liver resident macrophages(also known as Kupffer cells,KCs)and infiltrating monocyte-derived macrophages(MoMF).There is a growing appreciation that hepatic macrophage is very plastic,and assumes diverse phenotypes and functions in response to micro-environmental *** this review,we will summarize studies on the role of hepatic macrophages in both intrinsic DILI and idiosyncratic DILI,followed by discussing the prognostic and therapeutic potentials of targeting hepatic macrophages and the obstacles in studying hepatic macrophages.

关键词： Hepatic macrophages Acetaminophen(APAP) Drug Liver injury Intrinsic drug-induced liver injury(DILI) Idiosyncratic DILI

Hyocholic acid and glycemic regulation:comments on‘Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism’

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Journal of Molecular Cell Biology 2021年第6期13卷 460-462页

作者： Wei Jia cynthia Rajani Xiaojiao Zheng Weiping Jia Center for Translational Medicine Shanghai Key Laboratory of Diabetes MellitusDepartment of Endocrinology and MetabolismShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes InstituteShanghai 200233China School of Chinese Medicine Hong Kong Baptist UniversityKowloon TongHong Kong SARChina University of Hawaii Cancer Center HonoluluHI 96813USA

Hyocholic acid species(HCA,hyodeoxycholic acid,and their glycine and taurine conjugated forms)comprise 80%of the composition of pig bile(Haslewood,1956).An interesting fact about pigs is that they do not get diabetes even though they eat almost everything and in abundant amounts,a diabetes-promoting *** first use of pig bile for treatment of‘xiao-ke’.

关键词： homeostasis bile abundant

Commentary on two reports on animal models of COVID-19

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Animal Models and Experimental Medicine 2020年第2期3卷 115-116页

作者： cynthia Pekow International Council for Laboratory Animal Science BrusselsBelgium

In this communication,I have been invited to comment on the significance of two recent reports:The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice1 and Age-related Rhesus Macaque Models of COVID-19.2 The research was performed under the auspices of the Chinese Academy of Medical Sciences and Comparative Medicine Center,at Peking Union Medical College in Beijing,China.I am a Laboratory Animal Veterinarian,currently serving as the President of the International Council for Laboratory Animal Science(ICLAS).I have no affiliation or conflicting interest to *** opinion expressed here is my own.

关键词： Transgenic China. COV

Assessing the Effectiveness of Strategies in US Birth Cohort Screening for Hepatitis C Infection

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Journal of Clinical and Translational Hepatology 2020年第1期8卷 25-41页

作者： cynthia J.Tsay Joseph K.Lim Department of Internal Medicine Yale University School of MedicineNew HavenCTUSA Yale Liver Center Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA

Chronic hepatitis C infection in the USA is a highly morbid condition and current guidelines recommend one-time screening among the birth cohort(1945-1965).Understand-ing strategies to optimize screening can help inform future hepatitis C virus(HCV)screening guidelines.A focused literature search was performed using PubMed and manual abstract review from major hepatology conferences over the past 2 *** search strategy involved using Medical Subject Headings terms for hepatitis C,screening,birth cohort,baby boomers,and *** review was limited to data from the USA.A total of 327 articles were identified and 36 abstracts were included,with studies published between *** including clinician education,electronic medical record alerts,reflex HCV RNA testing,point-of-care testing,multisite(outpatient,inpatient,emergency department,endoscopy suite)initiatives,direct patient solicitation,and utilization of non-physician providers have increased HCV screening ***,broad imple-mentation remains less than *** include lack of patient acceptance to screening and engagement in the HCV care *** Veterans Affairs Healthcare System has achieved higher birth cohort screening rates through an integrated approach requiring high-level engagement by leadership and institutional *** strategies for increasing birth cohort screening have been successful,but overall rates of HCV screening remain *** strat-egies can inform public health efforts to implement emerging national recommendations for expansion of HCV screening to all *** age 18 or older.

关键词： Hepatitis C Epidemiology HCV antibody Screening Birth cohort Baby boomers Care cascade Electronic medical records

Halogen-specific total organic halogen analysis： Assessment by recovery of total bromine

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Journal of Environmental Sciences 2017年第8期29卷 340-348页

作者： Markus Langsa Sebastien Allard Ina Kristiana Anna Heitz cynthia A.Joll Curtin Water Quality Research Centre Department of Chemistry Curtin University Perth Western Australia 6102 Australia Department of Civil Engineering Curtin University Perth Western Australia 6102 Australia Jurusan Kimia Fakultas Matematika dan Ilmu Pengetahuan AlamUniversitas PapuaManokwaripapua Barat 98314Indonesia

Determination of halogen-specific total organic halogen（TOX） is vital for studies of disinfection of waters containing bromide, since total organic bromine（TOBr） is likely to be more problematic than total organic chlorine. Here, we present further halogen-specific TOX method optimisation and validation, focusing on measurement of TOBr. The optimised halogen-specific TOX method was validated based on the recovery of model compounds covering different classes of disinfection by-products（haloacetic acids, haloacetonitriles,halophenols and halogenated benzenes） and the recovery of total bromine（mass balance of TOBr and bromide concentrations） during disinfection of waters containing dissolved organic matter and bromide. The validation of a halogen-specific TOX method based on the mass balance of total bromine has not previously been reported. Very good recoveries of organic halogen from all model compounds were obtained, indicating high or complete conversion of all organic halogen in the model compound solution through to halide in the absorber solution for ion chromatography analysis. The method was also successfully applied to monitor conversion of bromide to TOBr in a groundwater treatment plant. An excellent recovery（101%）of total bromine was observed from the raw water to the post-chlorination stage. Excellent recoveries of total bromine（92%–95%） were also obtained from chlorination of a synthetic water containing dissolved organic matter and bromide, demonstrating the validity of the halogen-specific TOX method for TOBr measurement. The halogen-specific TOX method is an important tool to monitor and better understand the formation of halogenated organic compounds, in particular brominated organic compounds, in drinking water systems.

关键词： Total organic bromine Dissolved organic matter Bromide Chlorination Drinking water Health effects

Stem cell gene therapy:the risks of insertional mutagenesis and approaches to minimize genotoxicity

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Frontiers of Medicine 2011年第4期5卷 356-371页

作者： Chuanfeng Wu cynthia E.Dunbar Hematology Branch National HeartLung and Blood InstituteNational Institutes of HealthBethesdaMD 20892USA

Virus-based vectors are widely used in hematopoietic stem cell(HSC)gene therapy,and have the ability to integrate permanently into genomic DNA,thus driving long-term expression of corrective genes in all hematopoietic *** date,HSC gene therapy has been successfully employed in the clinic for improving clinical outcomes in small numbers of patients with X-linked severe combined immunodeficiency(SCID-X1),adenosine deaminase deficiency(ADA-SCID),adrenoleukodystrophy(ALD),thalassemia,chronic granulomatous disease(CGD),and Wiskott-Aldrich syndrome(WAS).However,adverse events were observed during some of these HSC gene therapy clinical trials,linked to insertional activation of proto-oncogenes by integrated proviral vectors leading to clonal expansion and eventual development of *** studies have been performed to understand the molecular basis of vector-mediated genotoxicity,with the aim of developing safer vectors and lower-risk gene therapy *** review will summarize current information on the mechanisms of insertional mutagenesis in hematopoietic stem and progenitor cells due to integrating gene transfer vectors,discuss the available assays for predicting genotoxicity and mapping vector integration sites,and introduce newlydeveloped approaches for minimizing genotoxicity as a way to further move HSC gene therapy forward into broader clinical application.

关键词： gene therapy hematopoietic stem cells insertional mutagenesis genotoxicity induced pluripotent stem cell

Effects of temperature and hydric environment on survival of the Panamanian Golden Frog infected with a pathogenic chytrid fungus

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Integrative Zoology 2010年第2期5卷 143-153页

作者： Heidi M.BUSTAMANTE Lauren J.LIVO cynthia CAREY Department of Integrative Physiology University of ColoradoBoulderColoradoUSA

Considerable controversy exists concerning whether or not climate changes(particularly global warming)are causing outbreaks of a lethal amphibian pathogen,the chytrid fungus Batrachochytrium dendrobatidis(Longcore,Pessier&*** 1999).In the present study,groups of Panamanian golden frogs(Atelopus zeteki Dunn,1993),a critically endangered amphibian thought to be nearly extinct in Panama,were exposed to varying dosages of zoospores of Batrachochytrium dendrobatidis,temperatures and hydric environments in order to learn whether this species is susceptible to this pathogen and,if so,how environmental factors affect *** pathogen proved to be highly lethal for *** exposed to a dosage of 100 Bd zoospores survived significantly(P<0.0001)longer than those that had been exposed to 104 or 106 *** frogs housed at 23℃survived significantly(P<0.0001)longer than those that were housed at 17℃.Exposed frogs held in dry conditions survived significantly longer than those in wet conditions(P<0.0001).As a laboratory study,these results do not directly test hypotheses about the relation between climate change and the decline of these frogs in the field,but they inform the discussion about how environmental conditions can have an impact on the interaction between a susceptible amphibian and this *** data do not support the contention that rising global temperatures are necessary to cause the death of amphibians infected with this pathogen because the pathogen was equally lethal at 17 as at 23℃,and frogs at the warmer temperature lived significantly longer than those at the cooler one.

关键词： amphibian declines Atelopus zeteki Batrachochytrium dendrobatidis chytridiomycosis climatelinked-epidemic hypothesis

Genotypic diversity of a dominant C_(4) grass across a long-term fire frequency gradient

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Journal of Plant Ecology 2013年第6期6卷 448-458页

作者： cynthia C.Chang Melinda D.Smith Department of Ecology and Evolutionary Biology Yale UniversityNew HavenCT 06511USA Department of Biology University of WashingtonSeattleWA 98195USA Department of Biology Colorado State UniversityFort CollinsCO 80523USA

Aims and Methods Diversity-disturbance research has focused on community diversity,but disturbance frequency could impact diversity within species as well,with important consequences for community diversity and ecosystem *** examined patterns of genetic diversity of a dominant grass species,Andropogon gerardii,in native North American tallgrass prairie sites located in eastern Kansas that have been subjected to a gradient of fire frequency treatments(burned every 1,2,4 or 20 years)since the *** addition,we were able to assess the relationships between genetic diversity of ***,species diversity and productivity across this range of fire *** Findings We found no significant relationships between genetic diversity of *** at the local scale(1 m^(2) plot level)and disturbance frequency(burned 2 to 32 times over a 38-year period).However,at the site level(*** all plots sampled within a site,~100 m^(2))there were differences in genotype richness and composition,as well as genomic dissimilarity among individuals of *** richness was greatest for the site burned at an intermediate(4-year)frequency and lowest for the infrequently(20-year)burned *** addition,genotypes found in the frequently burned sites were more similar from each other than expected by random chance than those found in the infrequently burned *** composition of *** was not significantly different between the frequently burned sites(annual vs.2 year)but did differ between frequently burned and infrequently burned sites(1 and 2 year vs.4 and 20 year,etc.).Together,these results suggest site-level ecological sorting of genotypes in intact prairie across a broad gradient of disturbance frequencies,likely driven by alterations in environmental *** fire promotes the abundance of dominant grass species,reduces plant community diversity and impacts ecosystem processes such as *** study suggests that

关键词： Andropogon gerardii disturbance frequency genetic relatedness genetic-species diversity relationship genotype richness intermediate disturbance hypothesis productivity tallgrass prairie