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Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction

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World Journal of Gastroenterology 2018年第16期24卷 1748-1765页

作者： michelle l boland Stephanie Oldham Brandon B boland Sarah Will Jean-Martin lapointe Silvia Guionaud Christopher J Rhodes James l Trevaskis Cardiovascular and Metabolic Diseases MedImmune LLC Pathology MedImmune Ltd. Pathology Drug Safety and MetabolismIMED Biotech UnitAstraZeneca

AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFlD) with or without progressive fibrosis: lep^(ob)/lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMlN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESUlTS When challenged with AMlN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMlN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMlN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMlN mice compared to FATZO AMlN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 Bl6 J control mice, but significantly perturbed in ob/ob mice. CONClUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is

关键词： Nonalcoholic steatohepatitis Steatosis Fibrosis Mitochondrial function Oxidative stress

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Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source

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World Journal of Gastroenterology 2019年第33期25卷 4904-4920页

作者： michelle l boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James l Trevaskis Henrik H Hansen Cardiovascular Renal and Metabolic DiseasesMedImmuneGaithersburgMD 20878United States Pharmacology GubraH■rsholm DK-2970Denmark

BACKGROUND The trans-fat containing AMlN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57Bl/6J mice with or without the lep^ob/lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of *** to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57Bl/6J *** To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated *** Male ob/ob mice were fed AMlN diet or a modified AMlN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57Bl/6J mice were fed the same diets for 28 *** and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)*** The GAN diet was more obesogenic compared to the AMlN diet and impaired glucose ***-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMlN diet.C57Bl/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same *** Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57Bl/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

关键词： Non-alcoholic steatohepatitis High-fat diet Mouse model Histopathology Fibrosis liver biopsy liver transcriptome

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ONECUT2 as a key mediator of androgen receptorindependent cell growth and neuroendocrine differentiation in castration-resistant prostate cancer

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Cancer Drug Resistance 2022年第1期5卷 165-170页

作者： WonSeok William Choi Julia l.boland Jianqing lin Division of Hematology/Oncology and Department of Medicine George Washington University HospitalGeorge Washington University School of Medicine and Health SciencesWashingtonDC 20037USA

Despite androgen dependence in a majority of castration-resistant prostate cancers,some cancer cells are independent of androgen receptor(AR)function,a feature of heterogeneity in prostate *** of the aggressive variants of prostate cancer that are AR independent is neuroendocrine prostate cancer(NEPC).This manuscript will focus on the new finding of human one cut domain family member 2(ONECUT2)transcription factor and its role in castration resistance,especially in NEPC.

关键词： Prostate cancers castration resistant ONECUT2 androgen receptor-independence neuroendocrine differentiation

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long-term persistence of T cell memory to HBsAg after hepatitis B vaccination

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World Journal of Gastroenterology 2004年第2期10卷 260-263页

作者： Ru-XiangWang GreetJ.boland JanvanHattum GijsbertC.deGast ShenyangCenterforDiseaseControlandPrevention Shenyang110031LiaoningProvinceChina DepartmentofGastroenterology UniversityHospitalUtrechttheNetherlands NetherlandsCancerInstitute AmsterdamtheNetherlands

AIM:To determine if the T cell memory to HBsAg can persist for a long time after hepatitis B (HB) ***: Thirty one vaccine recipients who werehealthcare workers (18 females and 13 males aged 34-58 years) from Utrecht University Hospital, Netherlands, and had previously received a standard course of vaccination for hepatitis B were investigated and another 9 unvaccinated healthy volunteers from the same hospital were used as the *** samples were taken just before the experiment to test serum anti-HBs levels and the subjects were classified into different groups according to their serum titers of antiHBs and vaccination *** peripheral blood mononuclear cells (PBMC) were isolated from freshly heparinized venous blood and the proliferative response of T lymphoo/tes to the recombinant hepatitis B surface antigen (HBsAg) was ***: Positive serum anti-HBs was found in 61.3%(19/31) vaccine recipients and a significant in vitro lymphocyte proliferative response to recombinant HBsAg was observed in all the vaccinees with positive *** anti-HBs level≤10IU/l was found in 38.7% (12/31) *** this study, we specially focused on lymphocyte proliferative response to recombinant HBsAg in those vaccine recipients with serum anti-HBsAg less than 10IU/*** of them had received a standard course of vaccination about 10 years before. T lymphocyte proliferative response was found positive in 7 of the 12 vaccine *** results confirmed that HBsAg-specific memory T cells remained detectable in the circulation for a long time after vaccination,even when serum anti-HBs level had been ***: The T cell memory to HBsAg can persist for at least 10 years after HB vaccination. Further booster injection is not necessary in healthy responders to HB vaccine.

关键词：乙型肝炎病毒乙肝表面抗原 T细胞存贮器存活率血清学检查细胞增殖

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l2 Syntactic Alignment in the Reading-Writing Integrated Continuation Task: Evidence From Chinese EFl learners’ Description of Motion Events

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Chinese Journal of Applied linguistics 2021年第3期44卷 292-313,430页

作者： Min WANG Qiao GAN Julie boland Xi’an Jiaotong University University of Michigan US

This study investigated how the mode in which the reading-writing integrated continuation task was conducted modulates the effects of second language(l2) syntactic alignment, through the English motion event construction with manner verbs. Ninety Chinese students were assigned to either of the two experimental groups or a control group, and they all experienced a pretest, an alignment phase and a posttest. In the alignment phase, the two experimental groups completed a reading-writing integrated continuation task but in different modes. For the multi-turn mode,participants reconstructed a picture story by continuing the episodes extracted from the story with one episode presented and continued at a time;for the single-turn mode, the first half of the same picture story was presented as a chunk, and then participants read and continued it. Results show that l2 learners aligned with the target structure in completing the story, and the alignment effect was retained in the posttest conducted after a delay of two weeks. Moreover, syntactic alignment was modulated by task mode with the multi-turn group exhibiting stronger immediate and longterm alignment effects. We conclude that the continuation task is a fruitful context for l2 structural alignment, and the magnitude of alignment effect hinges on interactive intensity.

关键词： reading-writing integrated continuation task syntactic alignment task mode interactive intensity motion event construction with manner verbs l2 learning

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Mutation of the Arabidopsis Calmodulin-like Protein CMl37 Deregulates the Jasmonate Pathway and Enhances Susceptibility to Herbivory

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Molecular Plant 2014年第12期7卷 1712-1726页

作者： Sandra S. Scholz Jyothilakshmi Vadassery Monika Heyer Michael Reichelt Kyle W. Bender Wayne A. Snedden Wilhelm boland Axel Mithofer Department of Bioorganic Chemistry Max Planck Institute for Chemical Ecology Hans-Knoll-StraBe 8 07745 Jena Germany Department of Biochemistry Max Planck Institute for Chemica Eco ogy Hans-Knoll-StraBe 8 07745 Jena Germany Department of Plant Biology University of Illinois Urbana IL 61801 USA Department of Biology Queen's University Kingston Ontario Canada Canada K7L 3N6

Throughout their life, plants are challenged by various abiotic and biotic stress factors. Among those are attacks from herbivorous insects. The molecular mechanisms underlying the detection of herbivores and the subsequent signal transduction are not well understood. As a second messenger, fluxes in intracellular Ca2＋ levels play a key role in mediating stress response pathways. Ca2＋ signals are decoded by Ca2＋ sensor proteins such as calmodulin-like proteins （CMls）. Here, we demonstrate that recombinant CMl37 behaves like a Ca2＋ sensor in vitro and, in Arabidopsis, AtCMl37 is induced by mechanical wounding as well as by infestation with larvae of the generalist lepidopteran herbivore Spodoptera littoralis. loss of function of CMl37 led to a better feeding performance of larvae suggesting that CMl37 is a positive defense regulator. No herbivory-induced changes in secondary metabolites such as glucosinolates or flavonoids were detected in cml37 plants, although a significant reduction in the accumulation of jasmonates was observed, due to reduced expression of JAR1 mRNA and cellular enzyme activity. Consequently, the expression of jasmonate-responsive genes was reduced as well. Summarizing, our results suggest that the Ca2＋ sensor protein, CMl37, functions as a positive regulator in Ca2＋ signaling during herbivory, connecting Ca2＋ and jasmonate signaling.

关键词： herbivory oral secretion jasmonates cytosolic calcium calmodulin-like proteins.

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蛋白酶抑制剂联合疗法与围生期HIV-1感染儿童的疾病严重程度及生活质量

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世界核心医学期刊文摘（儿科学分册） 2006年第6期2卷 54-56页

作者： Storm D.S. boland M.G. Gortmaker S.l. 唐彦 Franois-Xavier Bagnoud Center Bergen Building 65 Bergen St Newark NJ 07101-1709 United States Dr.

Objectives. This study examines quality of life (QOl) among school-aged children with perinatally acquired HIV infection and compares QOl outcomes between treatment groups that differ according to the use of protease inhibitor (PI) combination therapy (PI therapy). To gain insights into how PI therapy might influence QOl, associations between severity of illness and QOl were also investigated. Methods. Cross-sectional data for 940 children, 5 to 18 years of age, who were enrolled in Pediatric AIDS Clinical Trials Group late Outcomes Protocol 219 were used to examine domains of caregiver-reported QOl, as assessed with the General Health Assessment for Children, during 1999. The General Health Assessment for Children is an age-specific, modular, QOl assessment that was developed for the study with previously validated measures. QOl differences between treatment groups were estimated with linear and logistic regressions that controlled for sociodemographic characteristics (age, gender, raceethnicity, maternalcaregiver education, and respondent) and severity-of-illness indicators related to receipt of PI therapy (AIDS status, log10 CD4+cell counts, and height-for-age z scores). Results. The mean age of participants was 9.7 years. Most children were non-Hispanic black (54%) or Hispanic (31%), and 49%of the participants were female. At the 1999 study visit, ～14%of children had severe immune suppression ( lls), whereas 62%of children had ≥25%CD4+cells, ie, no immune suppression. Participants did exhibit some lag in growth, with mean height and weight z scores of-0.70 and-0.20, respectively. Twentyeight percent of the children were reported to have met criteria for AIDS at study entry (1993-1999). When treatment groups were compared, children receiving PI therapy (72%) were older, had lower CD4 +cell percentages, and had lower height and weight z scores than did those receiving non-PI therapies. They were also more likely to have met criteria for AIDS at study en

关键词： HIV-1感染疾病严重程度蛋白酶抑制剂学龄儿童围生期感染生活质量联合疗法 CD4^+细胞计数 logistic回归分析 QOl量表

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Genetic factors for differentiated thyroid cancer in French Polynesia:new candidate loci

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Precision Clinical Medicine 2023年第2期6卷 57-66页

作者： Monia Zidane Marc Haber Thérèse Truong Frédérique Rachédi Catherine Ory Sylvie Chevillard Hélène Blanché Robert Olaso Anne boland Éric Conte Mojgan Karimi Yan Ren Constance Xhaard Vincent Souchard Jacques Gardon Marc Taquet André Bouville Jean-François Deleuze Vladimir Drozdovitch Florent de Vathaire Jean-Baptiste Cazier University Paris-Saclay UVSQInsermGustave RoussyCESPTeam"Radiations Epidemiology"Villejuif 94805France Centre for Computational Biology University of BirminghamBirmingham B152TTUK Institute of Cancer and Genomic Sciences University of BirminghamBirmingham B152TTUK University Paris-Saclay UVSQInsermGustave RoussyCESPTeam"Exposome and Heredity"Villejuif 94805France Endocrinology Unit Territorial Hospital TaaoneF-98713PapeeteTahiti 98713French Polynesia CEA Laboratoire de Cancérologie FondamentaleInstitut de Biologie François JacobiRCMSREITLaboratoire de Cancérologie Expérimentale(LCE)UniversitéParis-SaclayFontenay aux Roses 92265France Fondation Jean Dausset-Centre d’Etude du Polymorphisme Humain Paris 75010France UniversitéParis-Saclay CEACentre National de Recherche en Génomique HumaineEvry 91057France U.S.R.2003(CNRS/UPF) Faa’aTahiti 98702France University of lorraine INSERM CIC 1433Nancy CHRUINSERM U1116Nancy 54500France Hydrosciences Montpellier Research Institute for DevelopmentCNRSUniversity of MontpellierMontpellier 62307France Research Institute for Development Center IRD on TahitiArueTahiti 98713French Polynesia National Cancer Institute(retired) BethesdaMD 20892USA Division of Cancer Epidemiology and Genetics National Cancer InstituteNIHDHHSBethesdaMD 20892USA

Background:Populations of French Polynesia(FP),where France performed atmospheric tests between 1966 and 1974,experience a high incidence of differentiated thyroid cancer(DTC).However,up to now,no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive *** research aimed to analyze the genetic factors of DTC risk among the native FP ***:We analyzed more than 300000 single nucleotide polymorphisms(SNPs)genotyped in 283 DTC cases and 418 matched controls born in FP,most being younger than 15 years old at the time of the first nuclear *** analyzed the genetic profile of our cohort to identify population *** then completed a genome-wide analysis study on the whole ***:We identified a specific genetic structure in the FP population reflecting admixture from Asian and European *** identified three regions associated with increased DTC risk at 6q24.3,10p12.2,and *** lead SNPs at these loci showed respective p-values of 1.66×10^(−7),2.39×10^(−7),and 7.19×10^(−7) and corresponding odds ratios of 2.02,1.89,and ***:Our study results suggest a role of the loci 6q24.3,10p12.2 and 17q21.32 in DTC ***,a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian ***,the functional impact of these three new loci needs to be further explored and validated.

关键词： differentiated thyroid cancer population genetics genetic susceptibility

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24例纵隔和胸腔脂肪肉瘤的临床病理和分子遗传学研究:强调少见的多样性组织学特征(英)

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诊断病理学杂志 2013年第2期20卷 M0004-M0004页

作者： boland JM 段瑞解放军306医院病理科

发生于纵隔的脂肪肉瘤罕见，多数此类研究报道早于当前基于遗传学的分类系统。作者报告了60年间遇到的一组胸部脂肪肉瘤的临床和分子遗传学特征，使用最新的WHO分类对24例确诊病例进行再分类，使用荧光原位杂交检测了部分病例CPM基因扩... 详细信息

发生于纵隔的脂肪肉瘤罕见，多数此类研究报道早于当前基于遗传学的分类系统。作者报告了60年间遇到的一组胸部脂肪肉瘤的临床和分子遗传学特征，使用最新的WHO分类对24例确诊病例进行再分类，使用荧光原位杂交检测了部分病例CPM基因扩增和／或DDIT3基因重排。24例中13例为男性，1l例为女性（中位年龄53岁，范围15～73岁）。其中8例是高分化脂肪肉瘤，6例为去分化脂肪肉瘤（3例CPM＋），7例多形性脂肪肉瘤（2例CPM-，1例DDIT3-），2例黏液性脂肪肉瘤，1例不能分类的脂肪肉瘤（CPM和DDIT3均一）。

关键词：去分化脂肪肉瘤分子遗传学临床病理组织学特征纵隔多样性多形性脂肪肉瘤黏液性脂肪肉瘤

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CT偶发肾上腺肿块的管理--美国放射学院(ACR)偶发病变委员会白皮书

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放射学实践 2018年第2期33卷 134-140页

作者： William W.Mayo-Smith Julie H.Song Giles l.boland Isaac R.Francis Gary M.Israel Peter J.Mazzaglia lincoln l.Berland Pari V.Pandharipande 张惠茅胡道予江新青刘爱连伍兵不详吉林大学第一医院放射科长春华中科技大学同济医学院附属同济医院放射科武汉华南理工大学附属广州市第一人民医院放射科广州大连医科大学附属第一医院放射科大连四川大学华西医院放射科成都

美国放射学院(American College of Radiology,ACR)偶发病变委员会(Incidental Findings Committee,IFC)针对CT和MRI上偶然发现的肾上腺肿块,提出了新的管理建议。该建议是对美国放射学院杂志(JACR)2010版肾上腺、肾脏、肝脏及胰腺偶发... 详细信息

美国放射学院(American College of Radiology,ACR)偶发病变委员会(Incidental Findings Committee,IFC)针对CT和MRI上偶然发现的肾上腺肿块,提出了新的管理建议。该建议是对美国放射学院杂志(JACR)2010版肾上腺、肾脏、肝脏及胰腺偶发病变管理白皮书中肾上腺部分的更新。由腹部放射科医师和1位内分泌外科医生组成的肾上腺亚组委员会制定了该方案。该方案结合已发表的文献和专家意见,经过反复推敲最终达成共识。该方案依据患者的特征和图像的特点对偶然发现的肾上腺肿块进行分类。对于每种特定的组合,总结良性或惰性的特征(足以终止随访),并提出后续管理建议。该方案涵盖了很多、但并非适用于所有的病理及临床情况,旨在通过提供肾上腺偶发肿块的管理意见以提升医疗质量。

关键词：肾上腺结节偶发病变偶发瘤

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