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Cellular & Molecular Immunology 2020年第4期17卷 418-420页

作者： Hussein Issaoui Mélissa Ferrad Nour Ghazzaui Sandrine Lecardeur Jeanne Cook-Moreau François Boyer Yves Denizot uMR CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(CSR),in which the constant(C)μgene of IgM is substituted with C_(γ),C_(ε),or C_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding C regions except for Cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor *** deaminates C into u on single-stranded DNA by targeting the WRCY(W=A/T,R=A/G,and Y=C/T)hot motif and,to a lesser extent,the SYC(S=G/C,Y=C/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEC)*** APOBEC genes,a family of evolutionarily conserved cytidine deaminases,APOBEC3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEC3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEC3 gene is present in rodents,seven copies of each APOBEC3 gene are found in humans.

关键词： immunity involvement thereby

Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

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World Journal of Gastroenterology 2022年第36期28卷 5324-5337页

作者： Gael Roth Yann Teyssier Maxime Benhamou Mélodie Abousalihac Stefano Caruso Christian Sengel Olivier Seror Julien Ghelfi Arnaud Seigneurin Nathalie Ganne-Carrie Elia Gigante Lorraine Blaise Olivier Sutter Thomas Decaens Jean-Charles Nault univ.Grenoble-Alpes Grenoble 38058France Department of Hepatology Gastroenterology and Digestive OncologyCHU Grenoble AlpesGrenoble 38043France Institute for Advanced Biosciences INSERM U1209/CNRS UMR 5309Grenoble 38043France Department of Radiology CHU Grenoble AlpesGrenoble 38043France Department of Radiology CHU Avicenne-APHPBobigny 93000France Functional Genomics of Solid Tumors Laboratory Centre de Recherche des Cordeliers-INSERM UMR 1138InsermUniversitéParisParis 75006France unitéde Formation et de Recherche SantéMédecine et Biologie Humaine UniversitéParis NordParis 93430France Service d'Epidémiologie et Evaluation Médicale CHU Grenoble AlpesGrenoble 38043France Department of Hepatology CHU Avicenne-APHPBobigny 93000France

BACKGROuND At the diagnosis of hepatocellular carcinoma(HCC),more than 90%of HCC patients present cirrhosis,a clinical condition often associated to *** is an indirect marker of malnutrition assessable on computed tomography(CT).AIM To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial(chemo)-*** Patients with HCC treated by a first session of trans-arterial(chemo)embolization and an available CT scan before treatment were *** was assessed using skeletal muscle index at baseline and at the first radiological *** response was recorded after the first session of treatment using *** Of 225 patients treated by trans-arterial bland embolization(n=71)or trans-arterial chemoembolization(n=154)for HCC between 2007 and 2013,Barcelona Clinic of Liver Cancer stage was A,B,and C in 27.5%,55%,and 16.8%of cases,*** was present in 57.7%of the *** with sarcopenia presented a higher rate of progressive disease(19%vs 8%,P=0.0236),a shorter progression-free survival(8.3 vs 13.2 mo,P=0.0035),and a shorter median overall survival(19.4 mo vs 35.5 mo,P=0.0149)compared with non-sarcopenic ***,patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis(P=0.0004).CONCLuSION Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial(chemo)-embolization for HCC.

关键词： Hepatocellular carcinoma Transarterial chemoembolization Bland embolization Sarcopenia Skeletal muscle index

Hepatitis C treatment in patients with substance use disorder:the faster the better

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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 129-131页

作者： Antonio Saviano Lucile Heroin Pierre Mayer Thomas F.Baumert Institut de Recherche sur les Maladies et Hépatiques(IVH) Inserm U1110StrasbourgFrance Institut Hospitalo-universitaire Service d’hépato-gastroentérologieHôpitaux Universitaires de StrasbourgStrasbourgFrance university of Strasbourg StrasbourgFrance Institut universitaire de France(IuF) ParisFrance

Hepatitis C virus(HCV)infection is a major cause of liver disease and hepatocellular carcinoma worldwide(1).HCV is a blood-borne infection and prevalence is particularly high in patients with a history of injective drug use or unsafe health care or sexual *** use disorder(SuD),and especially opioid misuse is a growing problem worldwide(2).This is particularly relevant in the united States(uS)where opioid misuse has raised sharply in the last years(3,4),termed also opioid *** is associated with an increase incidence of HCV infections and reinfections and associated liver disease(2,4).Moreover,alcohol use disorder is frequent in patients with SuD(5),representing another major risk factor for chronic liver disease in this *** with SuD often experience poor access to health care resulting in higher mortality(5,6).Finally,SuD is associated with psychiatric conditions and social problems such as housing instability,unemployment,and reduced access to medical care(7)which could result in a reduced access and compliance to HCV treatment.

关键词： patients mortality faster

Anti-hepatitis C virus drugs and kidney

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World Journal of Hepatology 2016年第32期8卷 1343-1353页

作者： Paul Carrier Marie Essig Marilyne Debette-Gratien Denis Sautereau Annick Rousseau Pierre Marquet Jérémie Jacques Véronique Loustaud-Ratti u850 inserm Université de Limoges Service d’Hépato-gastroentérologie CHU Limoges

Hepatitis C virus(HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease(CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in endstage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents(DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients(transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.

关键词： Nephrotoxicity 丙肝指导抗病毒的代理人肾结束阶段肾的疾病

COVID-19 and flu:conserved or specific immune signature?

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Cellular & Molecular Immunology 2021年第2期18卷 245-246页

作者： Christophe Paget François Trottein Centre d’Etude des Pathologies Respiratoires INSERM U1100Universitéde ToursFacultéde Médecine de Tours37000ToursFrance Centre d’Infection et d’Immunitéde Lille INSERM U1019CNRS UMR 9017Universitéde LilleCHU LilleUMS 2014-PLBSU1019Institut Pasteur de Lille59000LilleFrance

Respiratory viruses are a major cause of infectious disease and mortality *** respiratory viruses,emerging and well-known coronaviruses and influenza viruses cause seasonal epidemics and pandemics and rank as very important *** clinical signs of viral respiratory infections range from asymptomatic forms to life-threatening acute respiratory distress syndrome(ARDS,associated with a high mortality rate).Another reported cause of mortality is multiple organ *** ongoing pandemic of coronavirus disease 19(COVID-19,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2))is a serious public health ***-CoV-2 infection induces to a clinical signature distinct from that associated with other types of pneumonia,and SARS-CoV-2 differs from influenza viruses with regard to target cells and replicative *** morbidity and mortality rates are higher for COVID-19 than for seasonal influenza.

关键词： mortality acute respiratory

Clinical imaging factors of excellent outcome after thrombolysis in large- vessel stroke: a THRACE subgroup analysis

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Stroke & Vascular Neurology 2021年第4期6卷 631-639页

作者： Nolwenn Riou-Comte Benjamin Gory Marc Soudant François Zhu Yu Xie Lisa Humbertjean Gioia Mione Catherine Oppenheim Francis Guillemin Serge Bracard Sébastien Richard on behalf of the THRACE investigators Department of Neurology-Stroke unit CIC-P 1433INSERMU1116Universitéde LorraineNancy Regional University Hospital CenterNancyFrance Department of Diagnostic and Therapeutic Neuroradiology INSERM U1254IADIUniversitéde LorraineNancy Regional University Hospital CenterNancyFrance Clinical Investigation Centre-Clinical Epidemiology 1433 INSERMUniversitéde LorraineNancy Regional University Hospital CenterNancyFrance Department of Neuroradiology INSERM U894UniversitéParis-DescartesSainte-Anne HospitalParisFrance 不详

Background For patients with stroke with large-vessel occlusion(LVO),study of factors predicting response to intravenous thrombolysis(IVT)would allow identifying subgroups with high expected gain,and those for whom it could be considered as futile,and even *** patients included in the Mechanical Thrombectomy After Intravenous Alteplase vs Alteplase Alone After Stroke trial,we investigated clinical-imaging factors associated with optimal response to *** We included patients receiving IVT *** outcome was defined by a 3-month modified Rankin Scale(mRS)score≤***-imaging predictors were assessed on multivariate analysis after multiple *** predictive performance of the model was assessed with the *** Among 247 patients with LVO treated with IVT alone,77(31%)showed 3-month mRS≤*** of 3-month mRS≤1 were no medical history of hypertension(OR 2.43;95%CI 1.74 to 3.38;p=0.007);no current smoking(OR 2.76;95%CI 1.79 to 4.26;p=0.02);onset-to IVT time(OR 0.47 per hour increase;95%CI 0.23 to 0.78;p=0.003);diffusion-weighted imaging(DWI)volume(OR 0.78 per 10 mL increase;95%CI 0.68 to 0.89;p=0.0004);presence of susceptibility vessel sign(SVS)(OR 7.89;95%CI 1.65 to 37.78;p=0.01)and SVS length(OR 0.87 per mm increase;95%CI 0.80 to 0.94;p=0.001).The prediction models showed a C-statistic=0.79(95%CI 0.79 to 0.80).Conclusions In patients with stroke with anterior-circulation LVO treated with IVT alone,predictors of excellent outcome at 3 months were no medical history of hypertension or current smoking,reduced onset-to IVT time,small DWI volume,presence of SVS and short SVS *** predictive factors could help practitioners in decision-making for IVT implementation in reperfusion strategies,all the more for the drip and ship *** registration number NCT01062698.

关键词： thrombolysis Clinical assessed

IgD class switch recombination is not controlled through the immunoglobulin heavy chain 3′ regulatory region super-enhancer

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Cellular & Molecular Immunology 2017年第10期14卷 871-874页

作者： Hussein Issaoui Nour Ghazzaui Alexis Saintamand Yves Denizot François Boyer uMR CNRS 7276 University of LimogesCBRS87025 LimogesFrance Present address:inserm u1236 UniversitéRennes 1RennesFrance

In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ variable region and Cμand Cδheavy chain constant exons.1 After encountering antigen,B cells undergo class switch recombination(CSR)by which the Cμgene is substituted with Cγ,Cεor Cα,thereby generating IgG,IgE and IgA antibodies of the same antigenic specificity but with new effector *** requires the DNA-editing enzyme activation-induced deaminase(AID).

关键词： functions. substituted thereby

TAK1 Deficiency in Macrophages Increases Host Susceptibility to Leishmania Infection

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感染微生物与疾病(英文) 2023年第3期5卷 127-136页

作者： Xiankai Cao Kossiwa C.Kokou Shi Yu Mengdan Chen Junling Niu HervéLecoeur Eric Prina Gerald F.Späth Guangxun Meng The Center for Microbes Development and HealthCAS Key Laboratory of Molecular Virology&ImmunologyUniversity of Chinese Academy of SciencesShanghaiChina Institute Pasteur Paris City UniversityINSERM U1201Molecular Parasitology and Signalling UnitParisFrance Pasteurien College Soochow UniversitySuzhouChina Nanjing Advanced Academy of Life and Health NanjingChina.

Leishmania parasites mainly infect macrophages and may cause severe immunopathologies in their host,which are called *** the current work,we infected human and mouse macrophages in vitro with Leishmania major,an etiological agent of cu-taneous leishmaniasis,and found that inhibition or deletion of the transforming growth factorβ–activated kinase 1(TAK1)gene re-sulted in increased parasite *** vivo,following a challenge with ***,mice with a macrophage-specific deletion of TAK1 showed increased clinical signs and higher parasite loads compared with wild-type ***1 deficiency in mouse macro-phages led to biased Th2 cell responses during the acute stage of infection,characterized by a decrease in interferon-γexpression,and increased expression of IL-4,IL-5 and ***,we found that,in the late stage of *** infection,excessive Th2-related cytokines led to high arginase 1 expression in mouse tissues and a significant reduction of NO production both locally and system-ically,resulting in compromised control of *** findings suggest that TAK1 plays a vital role in host resistance to Leish-mania infection.

关键词： TAK1 macrophage Leishmania major arginase 1 nitric oxide

Host/genetic factors associated with COVID-19 call for precision medicine

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Precision Clinical Medicine 2020年第3期3卷 228-234页

作者： Alain R.Thierry Research Institute of Cancerology of Montpellier INSERM U1194IRCMICMMontpellier UniversityMontpellier F-34298France

If the current rate of infection are to be better managed,and future waves of infection kept at bay,it is absolutely necessary that the conditions and mechanisms of exposure to Severe Acute Respiratory Syndrome-Coronavirus 2(SARS-CoV-2)be better understood,as well as the downstream severe or lethal clinical *** the identification of notable comorbidities has now helped to define broad risk groups,the idiosyncratic responses of individual patients can generate unexpected clinical deterioration that is difficult to predict from initial clinical ***,physicians caring for patients with COVID-19 face clinical dilemmas on a daily *** ability to decipher individual predispositions to SARS-CoV-2 infection or severe illness,in light of variations in host immunological and inflammatory responses,in particular as a result of genetic variations,would be of great benefit in infection *** this end,this work associates the description of COVID-19 clinical complications,comorbidities,sequelae,and environmental and genetic *** also give examples of underlying genomic susceptibility to COVID-19,especially with regard to the newly reported link between the disease and the unbalanced formation of neutrophil extracellular *** a consequence,we propose that the host/genetic factors associated with COVID-19 call for precision medicine in its *** is to our knowledge the first article describing elements towards precision medicine for patients with COVID-19.

关键词： COVID-19 neutrophil extracellular traps sequelae genetic factors host factors circulating DNA

Targeted therapies in breast cancer:New challenges to fight against resistance

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World Journal of Clinical Oncology 2017年第2期8卷 120-134页

作者： Viviana Masoud Gilles Pagès university Nice Sophia Antipolis Institute for Research on Cancer and Aging of Nice CNRS UMR7284/INSERM U 1081

Breast cancer is the most common type of cancer found in women and today represents a significant challenge to public health. With the latest breakthroughs in molecular biology and immunotherapy, very specific targeted therapies have been tailored to the specific pathophysiology of different types of breast cancers. These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. However, the main challenge to be further investigated still remains the emergence of therapeutic resistance mechanisms, which develop soon after the onset of therapy and need urgent attention and further elucidation. What are the recent emerging molecular resistance mechanisms in breast cancer targeted therapy and what are the best strategies to apply in order to circumvent this important obstacle? The main scope of this review is to provide a thorough update of recent developments in the field and discuss future prospects for preventing resistance mechanisms in the quest to increase overall survival of patients suffering from the disease.

关键词： Breast cancers Resistance Human epidermal growth factor receptor 2 Angiogenesis Triple negative Immune tolerance