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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

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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

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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

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Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-B cell stage

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Cellular & Molecular Immunology 2019年第7期16卷 668-670页

作者： Nour Ghazzaui Hussein Issaoui Ophélie Alyssa Martin Alexis Saintamand Jeanne Cook-Moreau Yves denizot François Boyer CNRS uMR 7276 Inserm U1262Universitéde LimogesLimogesFrance Present address:inserm u1236 UniversitéRennes 1RennesFrance

Due to their impact on nuclear organization,enhancers are master regulators of cell fate.1,2 The immunoglobulin heavy chain(IgH)locus undergoes numerous changes(such as transcription,accessibility,DNA breaks,and mutations)throughout B-cell *** of these events are controlled by the IgH 3′regulatory region(3′RR).The 3′RR is the master control element of mature B-cell IgH transcription,3 somatic hypermutation(SHM),4,5 conventional class switch recombination(CSR),4,6–10 and locus suicide recombination(LSR).11 In contrast,the 3′RR is expected to be dispensable for V(D)J recombination.12,13 During Bcell development,the heavy and light chain loci are poised for their VDJ and VJ rearrangements,*** IgH locus rearranges first,with D-J joining at the pro-B-cell stages,followed by V-DJ joining at the pre-B-cell *** Igk locus is poised for VJ rearrangements at the pre-B cell stage.

关键词： effect joining recombination

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deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

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Neural Regeneration Research 2025年第8期20卷 2304-2306页

作者： Anthony Procès Sylvain Gabriele univ.Grenoble Alpes InsermU1216Grenoble Institut des NeurosciencesGrenobleFrance Mechanobiology&Biomaterials Group CIRMAPResearch Institute for BiosciencesUniversity of MonsMonsBelgium

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary *** minutes ... 详细信息

关键词： traumatic injury damage

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The IgH 3′ regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage

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Cellular & Molecular Immunology 2018年第3期15卷 289-291页

作者： Hussein Issaoui Nour Ghazzaui Alexis Saintamand Claire Carrion Christelle Oblet Yves denizot CNRS uMR 7276 CRIBLUniversitéde LimogesLimogesFrance inserm u1236 UniversitéRennes 1RennesFrance

The bone marrow-derived B2 population represents the vast majority of bone marrow,blood,lymph node and splenic *** B1 B-cells mostly originate during embryonic life in the liver and represent the main B-cell population in the pleural and peritoneal cavities.1,2,3,4,5 B1 and B2 B-cells differ in their origin,antigen specificity,cell surface markers,tissue distribution and capacity for class switch recombination(CSR).Schematically,B1 B-cells appear earlier than B2 B-cells during fetal development and maintain their self-renewal ability throughout their life.

关键词： maintain specificity mostly

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Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第8期14卷 1182-1191页

作者： Justin Monnier Claire Piquet-Pellorce Jean-Jacques Feige Orlando Musso Bruno Clément Bruno Turlin Nathalie Théret Michel Samson inserm u620 université de rennes 1 IFR140 2 avenue du Pr. Léon Bernard Rennes cedex 35043 France inserm u522 Rennes France inserm u878 Grenoble France Service d'Anatomo-pathologie CHU Pontchaillou Rennes France

AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF （an angiogenesis marker）, vWF （an endothelial cell marker） and to CD68 （a monocyte/macrophage marker）. Furthermore, the rnRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochernistry and immunocytochemistry.RESuLTS： PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/13v8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC,as expected. In addition, out of all isolated liver cells examined, only Kupffer cells （liver resident macrophages） express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLuSION： In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.

关键词： Prokineticin Hepatocellular carcinoma PK2/Bv8 Angiogenesis Kupffer cells Vascular endothelial growth factor Liver

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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

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Proteomic analysis of adipose tissue during the last weeks of gestation in pure and crossbred Large White or Meishan fetuses gestated by sows of either breed

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Journal of Animal Science and Biotechnology 2018年第3期9卷 558-573页

作者： F.Gondret B.Guével M.C.Père H.Quesnel Y.Billon *** L.Canario I.Louveau L.Liaubet PEGASE Agrocampus OuestINRA Protim Inserm U1085 Irset Université Rennes 1 Campus de Beaulieu Gen ESI INRA Le Magneraud Gen Physe INRA INPT INPT-ENV Université de Toulouse

Background: The degree of adipose tissue development at birth may influence neonatal survival and subsequent health outcomes. despite their lower birth weights, piglets from Meishan sows(a fat breed with excellent maternal ability) have a higher survival rate than piglets from Large White sows(a lean breed). To identify the main pathways involved in subcutaneous adipose tissue maturation during the last month of gestation, we compared the proteome and the expression levels of some genes at d 90 and d 110 of gestation in purebred and crossbred Large White or Meishan fetuses gestated by sows of either ***: A total of 52 proteins in fetal subcutaneous adipose tissue were identified as differential y expressed over the course of gestation. Many proteins involved in energy metabolism were more abundant, whereas some proteins participating in cytoskeleton organization were reduced in abundance on d 110 compared with d 90. Irrespective of age,24 proteins differed in abundance between fetal genotypes, and an interaction effect between fetal age and genotype was observed for 13 proteins. The abundance levels of proteins known to be responsive to nutrient levels such as aldolase and fatty acid binding proteins, as wel as the expression levels of FASN, a key lipogenic enzyme, and MLXIPL, a pivotal transcriptional mediator of glucose-related stimulation of lipogenic genes, were elevated in the adipose tissue of pure and crossbred fetuses from Meishan sows. These data suggested that the adipose tissue of these fetuses had superior metabolic functionality, whatever their paternal genes. Conversely, proteins participating in redox homeostasis and apoptotic cel clearance had a lower abundance in Meishan than in Large White fetuses. Time-course differences in adipose tissue protein abundance were revealed between fetal genotypes for a few secreted proteins participating in responses to organic substances, such as alpha-2-HS-glycoprotein, transferrin and ***

关键词： Adipose tissue Fetus Genetics Maturity grade Proteome

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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

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