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Neural Regeneration Research 2025年第9期20卷 2581-2582页

作者： Marianne Bardy-Lagarde Narimène Asbelaoui Abdel Mouman Ghoumari umr1195 “Diseases and Hormones of the Nervous System”Inserm and University Paris-SaclayKremlin-BicêtreFrance

Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.

关键词： myelin CXCR4

Central role of altered phosphodiesterase 2-dependent signaling in the pathophysiology of cognition-based brain disorders

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Neural Regeneration Research 2025年第8期20卷 2302-2303页

作者： Asma Boulksibat Alessandra Tempio Barbara Bardoni Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR7275Inserm U1323ValbonneFrance

The second messengers 3',5'-cyclic adenosine monophosphate(cAMP)and 3',5'-cyclic guanosine monophosphate(cGMP)modulate molecular pathways that are involved in a large variety of cellular *** the brain,these processes include neurogenesis,neuronal differentiation,activation and function of microglia,and synaptic plasticity,finally resulting in memory formation.

关键词： formation processes finally

Carbamylated lipoproteins in diabetes

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World Journal of Diabetes 2023年第3期14卷 159-169页

作者： Damien Denimal Department of Biochemistry University Hospital of DijonDijon 21079France inserm lnc umr1231 University of BurgundyDijon 21078France

Diabetic dyslipidemia is characterized by quantitative and qualitative abnormalities in *** addition to glycation and oxidation,carbamylation is also a post-translational modification affecting lipoproteins in *** with type 2 diabetes(T2D)exhibit higher levels of carbamylated low-density lipoproteins(cLDL)and high-density lipoproteins(cHDL).Accumulating evidence suggests that cLDL plays a role in atherosclerosis in *** levels have been shown to predict cardiovascular events and all-cause *** facilitates immune cell recruitment in the vascular wall,promotes accumulation of lipids in macrophages,and contributes to endothelial dysf-unction,endothelial nitric oxide-synthase(eNOS)inactivation and endothelial repair ***,cLDL induces thrombus formation and platelet *** the other hand,recent data have demonstrated that cHDL serum level is independently associated with all-cause and cardiovascular-related mortality in T2D *** relationship may be causative since the atheroprotective properties of HDL are altered after ***,cHDL loses the ability to remove cholesterol from macrophages,to inhibit monocyte adhesion and recruitment,to induce eNOS activation and to inhibit *** together,it seems very likely that the abnormalities in the biological functions of LDL and HDL after carbamylation contribute to atherosclerosis and to the elevated cardiovascular risk in diabetes.

关键词： Carbamylation Lipoprotein Diabetes Low-density lipoprotein High-density lipoprotein Myeloperoxidase

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

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Neural Regeneration Research 2025年第10期20卷 2938-2954页

作者： Danielle Fernezelian Philippe Rondeau Laura Gence Nicolas Diotel Universitéde La Réunion INSERMUMR 1188Diabète athérothrombose Thérapies Réunion Océan Indien(DéTROI)Saint PierreLa RéunionFrance

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these ***,the mechanisms by which these processes interact are not well *** this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound *** this end,we used zebrafish as a relevant model of neuroplasticity and brain repair ***,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days *** parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using *** found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were *** the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of ***,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial ***,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced *** conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this *** addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to

关键词： angiogenesis cerebral damage inflammation neurogenesis stab wound telencephalon vascular endothelial growth factor zebrafish

Plasma phospholipid transfer protein (PLTP) as an emerging determinant of the adaptive immune response

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Cellular & Molecular Immunology 2018年第12期15卷 1077-1079页

作者： Catherine Desrumaux Laurent Lagrost UniversitéMontpellier Montpellier F-34095France Team‘Environmental Impacts in Alzheimer’s Disease and Related Disorders’(EiAlz) InsermU1198Montpellier F-34095France EPHE Paris F-75007France LipSTIC LabEx Fondation de Coopération Scientifique Bourgogne-Franche ComtéDijon F-21000France inserm LNC UMR1231Dijon F-21000France University Bourgogne Franche-Comté LNC UMR1231Dijon F-21000France

Plasma phospholipid transfer protein(PLTP)is a multifunctional lipid *** addition to phospholipids,PLTP transports various amphipathic compounds,such as cholesterol,alphatocopherol,diacylglycerides,and *** addition to its impact on lipid metabolism and atherosclerosis development,PLTP has recently been reported to modulate inflammation and immune *** modulates the phagocytic activity of macrophages and microglial cells1,2 and increases the production of the pro-inflammatory cytokine interleukin 6(IL-6).3–5 In further support of the pro-inflammatory effect of PLTP,the expression level of IL-6 and the number of infiltrating macrophages in aortic tissue after experimental aneurysm induction were shown to be lower in PLTP-deficient mice than in wild-type mice;6 additionally,recombinant PLTP was shown to exert a direct pro-inflammatory effect on rheumatoid arthritis fibroblast-like synoviocytes,independent of its lipid transfer activity.7 Notably,despite its direct pro-inflammatory actions,PLTP can exert indirect antiinflammatory actions through its ability to transport and detoxify lipopolysaccharides in gram-negative bacteria.8,9 In humans,the majority of PLTP-associated proteins are involved in innate immunity and/or the inflammatory response in plasma,and PLTP activity is significantly increased in patients with bacterial infections and systemic *** addition to the key roles of PLTP in innate immunity,a recent publication from our group entitled“Plasma phospholipid transfer protein(PLTP)modulates adaptive immune functions through alternation of T-helper-cell polarization”10 demonstrated for the first time that PLTP can also modulate adaptive immune *** modulation occurred through a profound effect on CD4+T-cell polarization toward the pro-inflammatory Th1 *** novel property also supports the pro-inflammatory and pro-atherogenic effects of PLTP(Fig.1).

关键词： PLTP immunity metabolism

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

Tale of mitochondria and mitochondria-associated ER membrane in patient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry Timothy Barrett Sovan Sarkar I-STEM CECSCorbeil-EssonnesFrance UniversitéParis-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and Genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

Hype and hope of hepatic arterial infusion for colorectal cancer

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Hepatobiliary Surgery and Nutrition 2021年第2期10卷 235-237页

作者： François Ghiringhelli Centre de Recherche inserm lnc-umr1231 DijonFrance University of Burgundy Franche-Comté DijonFrance Department of Medical Oncology Centre Georges-François LeclercDijonFrance Cancer Biology Transfer Platform Centre Georges-François LeclercDijonFrance Genetic and Immunology Medical Institute DijonFrance

Contrary to most solid metastatic cancers,metastatic colorectal cancer could be cured by surgical removal of the metastasis in the context of lung or liver *** retrospective studies performed 20 years ago showed that surgery alone led to cure of the patient in about 35%of cases(1).To improve patient survival and to increase the cure rate,perioperative intravenous chemotherapy was *** a large EORTC trial among highly selected patients,perioperative FOLFOX regimen improved relapse-free survival with an absolute difference in 3-year PFS of 8.1%(28.1%in the surgery-only group vs.36.2%in the perioperative chemotherapy group)and there was a non-significant increase in overall survival(5-year overall survival was 51.2%in the perioperative chemotherapy group vs.47.8%in the surgery-only group)(2).Despite this somewhat disappointing result,perioperative FOLFOX regimen became the standard of care for the management of resectable colorectal liver metastasis.

关键词： colorectal chemotherapy metastasis

Click and bioorthogonal hyaluronic acid hydrogels as an ultra-tunable platform for the investigation of cell-material interactions

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Bioactive Materials 2023年第6期24卷 438-449页

作者： Nathan Lagneau Pierre Tournier Boris Halgand François Loll Yves Maugars Jérôme Guicheux Catherine Le Visage Vianney Delplace Nantes Université OnirisCHU NantesINSERMRegenerative Medicine and SkeletonRMeSUMR 1229F-44000France

The cellular microenvironment plays a major role in the biological functions of ***,biomaterials,especially hydrogels,which can be design to mimic the cellular microenvironment,are being increasingly used for cell encapsulation,delivery,and 3D culture,with the hope of controlling cell ***,much remains to be understood about the effects of cell-material interactions,and advanced synthetic strategies need to be developed to independently control the mechanical and biochemical properties of *** address this challenge,we designed a new hyaluronic acid(HA)-based hydrogel platform using a click and bioorthogonal strain-promoted azide-alkyne cycloaddition(SPAAC)*** approach facilitates the synthesis of hydrogels that are easy to synthesize and sterilize,have minimal swelling,are stable long term,and are *** provides bioorthogonal HA gels over an uncommonly large range of stiffness(0.5-45 kPa),all forming within 1-15 *** importantly,our approach offers a versatile one-pot procedure to independently tune the hydrogel composition(e.g.,polymer and adhesive peptides).Using this platform,we investigate the independent effects of polymer type,stiffness,and adhesion on the secretory properties of human adipose-derived stromal cells(hASCs)and demonstrate that HA can enhance the secretion of immunomodulatory factors by hASCs.

关键词： Hydrogels Click and bioorthogonal chemistry Hyaluronic acid Mesenchymal stromal cells Cell-material interactions Secretome

Inhibition of mitochondrial fatty acid oxidation in drug-induced hepatic steatosis

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Liver Research 2019年第3期3卷 157-169页

作者： Bernard Fromenty inserm UMR 1241Universitéde Rennes 1RennesFrance

Mitochondrial fatty acid oxidation(mtFAO)is a key metabolic pathway required for energy production in the liver,in particular during periods of *** major consequence of drug-induced impairment of mtFAO is hepatic steatosis,which is characterized by an accumulation of triglycerides and other lipid species,such as ***,the severity of this liver lesion is dependent on the residual mitochondrial b-oxidation ***,a severe inhibition of mtFAO leads to microvesicular steatosis,hypoglycemia and liver *** contrast,moderate impairment of mtFAO can cause macrovacuolar steatosis,which is a benign lesion in the short *** some drugs can induce both microvesicular and macrovacuolar steatosis,it is surmised that severe mitochondrial dysfunction could be favored in some patients by non-genetic factors(e.g.,high doses and polymedication),or genetic predispositions involving genes that encode proteins playing directly or indirectly a role in the mtFAO *** of drugs inducing steatosis include acetaminophen(APAP),amiodarone,ibuprofen,linezolid,nucleoside reverse transcriptase inhibitors,such as stavudine and didanosine,perhexiline,tamoxifen,tetracyclines,troglitazone and valproic *** several previous articles reviewed in depth the mechanism(s)whereby most of these drugs are able to inhibit mtFAO and induce steatosis,the present review is rather focused on APAP,linezolid and *** steatogenic drugs are indeed rarely discussed in the literature as regards their ability to impair mtFAO.

关键词： Drug-induced liver injury(DILI) Steatosis Mitochondria b-Oxidation Acetaminophen(APAP) Troglitazone