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NRF2 signaling cascade in amyotrophic lateral sclerosis:bridging the gap between promise and reality

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Neural Regeneration Research 2024年第5期19卷 1006-1012页

作者： Pauline Tarot Christelle Lasbleiz Jean-Charles Liévens MMDN Univ MontpellierEPHEINSERMMontpellierFrance CNRS ParisFranceEPHEINSERMMontpellierFrance

Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor *** include muscle weakness and atrophy,spasticity,and progressive ***,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral *** only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial *** difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis *** mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious *** the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and *** here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis C9orf72 NRF2 oxidative defense oxidative stress sulforaphane superoxide dismutase 1 TDP43

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

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 *** 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 *** 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 *** primary outcome was the proportion of ICu admissions for SAE during 5-year *** outcomes were ICu and hospital mortality,and the use of mechanical ventilation and *** analysis was performed to assess factors associated with ICu *** A total of 7049 admissions for SAE were *** 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 *** 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 *** use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine *** and hospital mortality rates *** 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 *** ICu admission for SAE remains uncommon,and the proportion of cases decreased over *** a slight increase in symptom severity during a 20-year period,ICu and hospital mortality *** requirin

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

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

关键词： NK cells Cell therapy Receptor engineering CAR

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 *** exhibit a unique combination of self-renewal potency,unlimited proliferation,and *** latter is evident by the ability of the isolated cells to differ-entiate spontaneously into multiple cell lineages,representing the three primary embryonic germ *** regulatory networks guide ESCs,directing their self-renewal and lineage-specific ***,or programmed cell death,emerges as a key event involved in sculpting and forming various organs and structures ensuring proper embryonic ***-ever,the molecular mechanisms underlying the dynamic interplay between diffe-rentiation and apoptosis remain poorly *** 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,*** 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 *** hanging drop method was adopted to generate embryoid bodies(EBs)and induce terminal differentiation of *** size of the generated EBs was measured in each condition compared to the wild *** the functional level,the percentage of cardiac differentiation was measured by calculating the number of beating cardiomyocytes in the manipulated mESCs compared to the *** the molecular level,quantitative reverse transcription-polymerase chain reaction was used to assess the mRNA expression of three cardiac markers:Troponin T,GATA4,and ***,troponin T protein expression was evaluated through immunofluorescence and western blot *** Our findings showed that the upregulation of Bcl-

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

Hybrid silver nanoparticles:Modes of synthesis and various biomedical applications

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Electron 2024年第2期2卷 196-218页

作者： Priyanka Singh Shivang Singh Balaji Maddiboyina SaiKrishna Kandalam Tomasz Walski Raghvendra A.Bohara Centre for Interdisciplinary Research D.Y.Patil Educational SocietyKolhapurIndia Department of Internal Medicine Rauta Hospital Pvt.LtdGaighatUdayapurNepal Department of Medical and Scientific Communications Scientific Writing ServicesFreyr Global Regulatory Solutions&ServicesHyderabadTelanganaIndia inserm u 1066 ‘Micro et Nanomédecines Biomimétiques-MINT’AngersFrance universitéAngers UMR-S1066AngersFrance Department of Biomedical Engineering Wroclaw University of Science and TechnologyWroclawPoland university of Galway

In the present day,there is a growing trend of employing new strategies to synthesize hybrid nanoparticles,which involve combining various functionalities into a single nanocomposite *** modern methods differ significantly from the traditional classical approaches and have emerged at the forefront of materials *** fabrication of hybrid nanomaterials presents an unparalleled opportunity for applica-tions in a wide range of areas,including therapy to *** focus of this review article is to shed light on the different modalities of hybrid nanoparticles,providing a concise description of hybrid silver nano-particles,exploring various modes of synthesis and classification of hybrid silver nanoparticles,and highlighting their ***-tionally,we discussed core-shell silver nanoparticles and various types of core and shell combinations based on the material category,such as dielectric,metal,or *** two primary classes of hybrid silver nanoparticles were also ***,various hybrid nanoparticles and their methods of synthesis were discussed but we emphasize silica as a suitable candidate for hybridization alongside metal *** choice is due to its hydrophilic surface qualities and high surface charge,which provide the desired repulsive forces to minimize aggregation between the metal nanoparticles in the liquid *** shell encapsulation also provides chemical inertness,robustness and the adaptability to the desired hybrid ***,among all the materials used to coat metal nanoparticles;silica is highly approved.

关键词： biomedical applications hybrid silver nanoparticles polyvinylpyrrolidone silica shell surface enhanced Raman spectroscopy

In vivo astrocyte reprogramming following spinal cord injury

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Neural Regeneration Research 2024年第3期19卷 487-488页

作者： Yannick N.Gerber Florence E.Perrin MMDN University of MontpellierEPHEINSERMMontpellierFrance Institut universitaire de France(IuF) ParisFrance

Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury *** absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic ***,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting *** other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal ***,astrocytes.

关键词： injury impairment programming

Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

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Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon Benjamin G.Chousterman Tomasz Skirecki Institut Pasteur ParisFrance Department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance inserm u942 University of ParisParisFrance Department of Translational Immunology and Experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

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 *** the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other *** 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 *** 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 ***-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared *** their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy ***,they impact GABAergic neurons and the excitation/inhibition *** rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock *** mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully *** sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory *** 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 *** this context,the Drosophila model,though underutilized,holds promise in shedding new light on these *** findings indicate its po

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