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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

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

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

EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma

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World Journal of Gastrointestinal Oncology 2018年第4期10卷 103-107页

作者： Corentin Richard Julie Niogret Romain Boidot Francois Ghiringhelli Platform of Transfer in Oncology Center GF LeclercDijon 21000France inserm u1231 Dijon 21000France university of Bourgogne Franche Comte Dijon 21000France Department of Medical Oncology Georges Francois Leclerc Cancer CenterDijon 21000France

Pancreatic acinar cell carcinoma(PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses. The analyses revealed in the liver metastasis an amplification of the EGFR gene. Accordingly, the patient was treated with off-label usage of panitumumab. We observed rapid response with necrosis of the liver metastasis, while no efficacy was observed in the primary tumor. An exome analysis of the primary tumor revealed amplification of HER2 and MET with EGFR amplification. Such amplifications are known as a resistance mechanism to anti EGFR therapy. Our results suggest that exome analysis may be helpful to highlight targets in rare cancers, such as PACC. EGFR amplification in this pathology should be determined and could be used as a biomarker to propose anti EGFR therapy.

关键词： Pancreatic cancer Acinar cell carcinoma Exome Genetic mutations Precision medicine

use of longitudinal magnetic resonance imaging in preclinical models of spinal cord injury

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Neural Regeneration Research 2019年第5期14卷 771-772页

作者： Harun Najib Noristani Florence Evelyne Perrin inserm u1198 University of Montpellier

Spinal cord injury(SCI)is a distressing event with grave socio/economic consequences to our *** response following SCI involves blood-spinal cord barrier breakdown,neuroinflammation and formation of a glial scar that altogether govern the feasibility of spontaneous axonal re-growth and limited functional *** advances in understanding SCI pathophysiology have been achieved using numerous transgenic mouse lines developed in different ***,there are inherent strain differences that affect inflammation,gliosis,axon regeneration and ultimately functional recovery after SCI.

关键词： Spinal cord injury(SCI) spinal cord injury

Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer

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World Journal of Gastroenterology 2010年第9期16卷 1150-1154页

作者： Boris Guiu Julie Vincent Séverine Guiu Sylvain Ladoire Pablo Ortega-Deballon Jean-Pierre Cercueil Bruno Chauffert Franois Ghiringhelli Department of Radiology INSERM U866University of BurgundyUniversity Hospital Department of Hepatology INSERM U866University of BurgundyUniversity Hospital Department of Oncology INSERM U866AVENIR TeamUniversity of Burgundy Department of Digestive Surgery INSERM U866University of BurgundyUniversity Hospital

Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug *** we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic *** patient was treated with a combination of gemcitabine and oxaliplatin using *** tolerance was excellent and a radiological complete response was obtained after 8 cycles of *** rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this *** of gemcitabine-oxaliplatin should be evaluated in further clinical trials.

关键词： Hepatic artery Chemotherapy Colon cancer Liver metastasis Gemcitabine Oxaliplatin Contrast media Computed tomography

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

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

Axonal protein synthesis in central nervous system regeneration:is building an axon a local matter?

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Neural Regeneration Research 2022年第5期17卷 987-988页

作者： Julia Schaeffer Stephane Belin universitéGrenoble Alpes InsermU1216Grenoble Institut NeurosciencesGrenobleFrance

Neurons of the mature central nervous system(CNS,mainly the brain and spinal cord)are unable to regenerate spontaneously after a lesion,in contrast to neurons of the peripheral nervous system(PNS).While the extraneuronal environment was long thought to be limiting,evidence was given less than 15 years ago that neurons themselves are critical players of their own regeneration(Park et al.,2008).Indeed,CNS neurons show a decline of axon growth capacity as they mature and after an ***,the role of axonal translation is actively explored in the paradigm of embryonic neuronal growth and in peripheral nerve injury and regeneration,but less is known about the role of local protein synthesis in regrowth of adult CNS *** we discuss how the current understanding of axonal translation in the CNS may contribute to the development of novel strategies to enhance axon regeneration in the injured CNS.

关键词： synthesis system local