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Translational machinery and translation regulation in axon regeneration

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Neural Regeneration Research 2025年第5期20卷 1392-1394页

作者： Homaira Nawabi Stephane Belin univ.Grenoble Alpes InsermU1216Grenoble Institut NeurosciencesGrenobleFrance

Over the centuries,the regeneration field has been puzzled by the dual response of the central nervous system(CNS-brain,spinal cord,cranial nervesⅠandⅡ)and the peripheral nervous system(PNS that refers to all the nerves that innervate muscles,skin,organs,bones among others).Even Ramon y Cajal had noticed that an injury to the PNS often leads to axon regrowth,in contrast to the CNS.

关键词： nerves organs muscles

Development of NK cell-based cancer immunotherapies through receptor engineering

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Cellular & Molecular Immunology 2024年第4期21卷 315-331页

作者： Audrey Page Nicolas Chuvin Jenny Valladeau-Guilemond Stéphane Depil Centre de Recherche en Cancérologie de Lyon UMR INSERM U1052 CNRS 5286Centre Léon BérardLyonFrance ErVimmune LyonFrance Centre Léon Bérard LyonFrance universitéClaude Bernard Lyon 1 LyonFrance

Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer treatment.Early clinical trials have shown promising outcomes,alongside satisfactory product efficacy and safety.Recent developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic capacities.This review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future directions.Most approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen restriction.This approach has increased the precision and potency of NK-mediated recognition and elimination of cancer cells.In addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target peptides.Indirect tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and signaling.Indeed,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular cytotoxicity.The ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been explored.Receptor-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced immunosuppression.Overall,receptor engineering has led to significant advances in NK cell-based cancer immunotherapies.As technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

关键词： NK cells Cell therapy Receptor engineering CAR

Severe asthma exacerbation:Changes in patient characteristics,management,and outcomes from 1997 to 2016 in 40 ICus in the greater Paris area

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Journal of Intensive Medicine 2024年第2期4卷 209-215页

作者： Romy Younan Jean Loup Augy Bertrand Hermann Bertrand Guidet Philippe Aegerter Emmanuel Guerot Ana Novara Caroline Hauw-Berlemont Amer Hamdan Clotilde Bailleul Francesca Santi Jean-Luc Diehl Nicolas Peron Nadia Aissaoui Intensive Care unit AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Intensive Care unit AP-HPSaint Antoine HospitalUniversités de SorbonneUniversitéPierre et Marie CurieParisFrance inserm u1136 ParisFrance Versailles Saint-Quentin-en-Yvelines university INSERM U1018Groupe Interrégional de Recherche Clinique et d'InnovationÎle-de-FranceFrance Respiratory Medicine Department AP-HPGeorges Pompidou European HospitalUniversitéde ParisParisFrance Innovative Therapies in Hemostasis INSERM UMR-S1140Universitéde ParisParisFrance Intensive Care unit and Biosurgical Research Lab(Carpentier Foundation) AP-HPGeorges Pompidou European HospitalParisFrance Paris-Cardiovascular-Research-Center INSERM U970ParisFrance

Background Despite advances in asthma treatments,severe asthma exacerbation(SAE)remains a life-threatening condition in adults,and there is a lack of data derived from adult patients admitted to intensive care units(ICus)for SAE.The current study investigated changes in adult patient characteristics,management,and outcomes of SAE over a 20-year period in 40 ICus in the greater Paris area.Methods In this retrospective observational study,admissions to 40 ICus in the greater Paris area for SAE from January 1,1997,to December 31,2016 were analyzed.The primary outcome was the proportion of ICu admissions for SAE during 5-year periods.Secondary outcomes were ICu and hospital mortality,and the use of mechanical ventilation and catecholamine.Multivariate analysis was performed to assess factors associated with ICu mortality.Results A total of 7049 admissions for SAE were recorded.For each 5-year period,the proportion decreased over time,with SAE accounting for 2.84%of total ICu admissions(n=2841)between 1997 and 2001,1.76%(n=1717)between 2002 and 2006,1.05%(n=965)between 2007 and 2011,and 1.05%(n=1526)between 2012 and 2016.The median age was 46 years(interquartile range[IQR]:32–59 years),55.41%were female,the median Simplified Acute Physiology Score II was 20(IQR:13–28),and 19.76%had mechanical ventilation.The use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine decreased.ICu and hospital mortality rates decreased.Factors associated with ICu mortality were renal replacement therapy,catecholamine,cardiac arrest,pneumothorax,acute respiratory distress syndrome,sepsis,and invasive mechanical ventilation(IMV).Non-survivors were older,had more severe symptoms,and were more likely to have received IMV.Conclusion ICu admission for SAE remains uncommon,and the proportion of cases decreased over time.Despite a slight increase in symptom severity during a 20-year period,ICu and hospital mortality decreased.Patients requiring IMV had a higher mortality rate.

关键词： Epidemiology Intensive care unit Mechanical ventilation Severe asthma exacerbation

Cardiac differentiation is modulated by anti-apoptotic signals in murine embryonic stem cells

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World Journal of Stem Cells 2024年第5期16卷 551-559页

作者： Amani Yehya Joseph Azar Mohamad Al-Fares Helene Boeuf Wassim Abou-Kheir Dana Zeineddine Ola Hadadeh Department of Anatomy Cell Biology and Physiological SciencesAmerican University of BeirutBeirut 1107-2020Lebanon inserm BiotisU1026University BordeauxBordeaux F-33000France Rammal Rammal Lab Physio-Toxicity Environmental TeamFaculty of SciencesLebanese UniversityNabatieh 0000Lebanon

BACKGROuND Embryonic stem cells(ESCs)serve as a crucial ex vivo model,representing epiblast cells derived from the inner cell mass of blastocyst-stage embryos.ESCs exhibit a unique combination of self-renewal potency,unlimited proliferation,and pluripotency.The latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ layers.Multiple regulatory networks guide ESCs,directing their self-renewal and lineage-specific differentiation.Apoptosis,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic development.How-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly understood.AIM To investigate the regulatory impact of apoptosis on the early differentiation of ESCs into cardiac cells,using mouse ESC(mESC)models-mESC-B-cell lym-phoma 2(BCL-2),mESC-PIM-2,and mESC-metallothionein-1(MET-1)-which overexpress the anti-apoptotic genes Bcl-2,Pim-2,and Met-1,respectively.METHODS mESC-T2(wild-type),mESC-BCL-2,mESC-PIM-2,and mESC-MET-1 have been used to assess the effect of potentiated apoptotic signals on cardiac differentiation.The hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of mESCs.The size of the generated EBs was measured in each condition compared to the wild type.At the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the control.At the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and NKX2.5.Additionally,troponin T protein expression was evaluated through immunofluorescence and western blot assays.RESuLTS Our findings showed that the upregulation of Bcl-2,Pim-2,and Met-1 genes led to a reduction in th

关键词： Mouse embryonic stem cells Self-renewal Apoptosis Cardiac differentiation B-cell lymphoma 2 PIM-2 Metallothionein-1

Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2141-2158页

作者： Frederiek Nuytens Vincent Drubay Clarisse Eveno Florence Renaud Guillaume Piessen Department of Digestive and Oncological Surgery University LilleClaude Huriez University HospitalLille 59000France Department of Digestive and Hepatobiliary/Pancreatic Surgery AZ GroeningeKortrijk 8500Belgium Cambrai Hospital Center and Sainte Marie Group of Hospitals of The Catholic Institute of LilleCambrai 59400France CNRS InsermUMR9020-U1277-CANTHER-CancerUniversity LilleCHU LilleLille 59000France

BACKGROuND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESuLTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperther

关键词： Colorectal cancer Signet-ring cell histology Poorly cohesive cells Systematic review Risk factors Prognosis Therapeutic management

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

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Neural Regeneration Research 2025年第5期20卷 1350-1363页

作者： Hui Li Laurent Seugnet Department of Neurology Xijing HospitalXi’anShaanxi ProvinceChina Centre de Recherche en Neurosciences de Lyon Integrated Physiology of the Brain Arousal Systems(WAKING)UniversitéClaude Bernard Lyon 1INSERM U1028CNRS UMR 5292BronFrance

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly

关键词： branched-chain amino acids cardiovascular health circadian clock drosophila insulin metabolism sleep γ-aminobutyric acid

Adult neurogenesis:a real hope or a delusion?

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Neural Regeneration Research 2024年第1期19卷 6-15页

作者： Ghulam Hussain Rabia Akram Haseeb Anwar Faiqa Sajid Tehreem Iman Hyung Soo Han Chand Raza Jose-Luis Gonzalez De Aguilar Neurochemicalbiology and Genetics Laboratory(NGL) Department of PhysiologyFaculty of Life SciencesGovernment College UniversityFaisalabadPunjabPakistan Department of Physiology School of MedicineClinical Omics InstituteKyungpook National UniversityDaeguKorea Department of Zoology Faculty of Chemistry and Life SciencesGovernment College UniversityLahorePakistan inserm U1118Mécanismes Centraux et Péripheriques de la NeurodégénérescenceStrasbourgFranceUniversitéde StrasbourgStrasbourgFrance

Adult neurogenesis,the process of creating new neurons,involves the coordinated division,migration,and differentiation of neural stem cells.This process is restricted to neurogenic niches located in two distinct areas of the brain:the subgranular zone of the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricle,where new neurons are generated and then migrate to the olfactory bulb.Neurogenesis has been thought to occur only during the embryonic and early postnatal stages and to decline with age due to a continuous depletion of neural stem cells.Interestingly,recent years have seen tremendous progress in our understanding of adult brain neurogenesis,bridging the knowledge gap between embryonic and adult neurogenesis.Here,we discuss the current status of adult brain neurogenesis in light of what we know about neural stem cells.In this notion,we talk about the importance of intra cellular signaling molecules in mobilizing endogenous neural stem cell prolife ration.Based on the current understanding,we can declare that these molecules play a role in targeting neurogenesis in the mature brain.However,to achieve this goal,we need to avoid the undesired proliferation of neural stem cells by controlling the necessary checkpoints,which can lead to tumorigenesis and prove to be a curse instead of a blessing or hope.

关键词： adult neurogenesis aging brain-derived neurotrophic factor dentate gyrus hippocampus neural stem cells neurotrophic factors Notch oxidative stress stem cells subgranular zone

Mediator contributes to IgH locus VDJ rearrangements by promoting usage of most distal V segments

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Cellular & Molecular Immunology 2020年第4期17卷 407-409页

作者： Iman Dalloul Zeinab Dalloul Sandrine Le Noir François Boyer Bernardo Reina-San-Martin Jeanne Cook-Moreau Michel Cogné uMR CNRS 7276 INSERM U1262Universite de LimogesLimoges 87025France inserm u1258 UMR CNRS 7104Institut de Genetique et de Biologie Moleculaire et CellulaireUniversitéde StrasbourgIllkirch 67400France

INTRODuCTION The immunoglobulin heavy(IgH)chain locus includes a large cluster of V,D and J segments spanning thousands of kilobases in mammals and its expression implies long-range 3D-regulation of various gene modifications.1 V(D)J recombination occurs during early B-cell ontogeny.2 It is regulated by multiple transcription factors and cis-regulatory elements,and most notably by the intronic 5′Eμelement located in the JH to Cμintron.3 The intergenic control region 1(IGCR1)located between the VH and D gene clusters inhibits rearrangement of the most DH-proximal VH gene segments,while promoting usage of distal VH gene segments.4 Other downstream elements of the locus,flanking its 3′end might have more subtle roles:while the large 3′regulatory region(3′RR)shows strong internal synergies2 and behaves as a superenhancer in mature B cells.Its deletion showed no influence on the VDJ repertoire and rather increased transcription of unrearranged V segments.3–5 Insulators binding CTCF farther downstream of the 3′RR were shown,however,to promote usage of distal VH segments.6 Altogether,there are strong indications that elements involved in long-distance regulation of transcription might also influence VDJ recombination.In-frame splicing of VDJ exons is also needed for full Ig expression.7 Given the functional importance of gene architecture and long-range interactions for the IgH locus physiology,we explored the dependence of the VDJ repertoire on Med1,a known actor of long-range enhancer interactions.

关键词： B cells mediator VDJ repertoire

Multi-Compartment SCFA Quantification in Human

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American Journal of Analytical Chemistry 2024年第6期15卷 177-200页

作者： Jérémy Monteiro Antoine Lefèvre Diane Dufour-Rainfray Adeline Oury Gabrielle Chicheri Laurent Galineau Hélène Blasco Lydie Nadal-Desbarats Patrick Emond Imaging Brain & Neuropsychiatry iBraiN u1253 Universit de Tours INSERM MetaboHub Tours Tours France CHRu de Tours Service de Mdecine Nuclaire in Vitro Tours France Service de Biochimie et Biologie Molculaire CHRU Tours France

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

关键词： LC-MS 3-Nitrophenylhydrazine Short-Chain Fatty Acids Human Biological Samples Quantification