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Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles méryl-Farelle Oye mintsa mi-mba Katherine Coulombe Cyntia Tremblay VincentÉmond martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe Neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada Institute of Nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated Laboratory(NutriNeuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et Néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada Département de médecine Facultéde MédecineUniversitéLavalQuebecQCCanada Département de Psychiatrie et Neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3

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Stepping up after spinal cord injury:negotiating an obstacle during walking

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Neural Regeneration Research 2025年第7期20卷 1919-1929页

作者： Alain Frigon Charly G.Lecomte department of Pharmacology-Physiology Faculty of Medicine and Health SciencesUniversitéde SherbrookeCentre de recherche du Centre Hospitalier Universitaire de SherbrookeSherbrookeQCCanada

Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate *** spinal cord injury,stepping over an obstacle becomes *** over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor *** information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain *** spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an ***,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.

关键词： biomechanics locomotion neurophysiology obstacle negotiation spinal cord injury

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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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c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

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World Journal of Gastroenterology 2008年第41期14卷 6339-6346页

作者： meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence michel Alain mauviel Dominique Bernuau Fanny Daniel Institut National de laSanté et de la recherche médicale U697 Hpital Saint-Louis Institut National de la Santé et de la recherchemédicale U591 Faculté de Médecine Necker Institut National de la Santé et de la recherchemédicale U773 Centre de Recherche Bichat Beaujon CRB3and Université Paris 7 Denis Diderot site Bichat

AIm： To investigate the effect of stable c-Fos over- expression on immortalized human hepatocyte （IHH） proliferation. metHODS： IHHs stably transfected with c-Fos （IHH- Fos） or an empty vector （IHH-C） were grown in me- dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins （Cyclin DI, E, A） cyclin dependent kinases （cdk） cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3β and epidermal growth factor receptor （EGF-R） were assayed by Western blotting. Analysis of O/c/in D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction （PCR） analysis. Stability of Cyclin DI was studied by cycloheximide blockade experiments. RESULTS： Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress- ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com- pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specific EGF-R tyro- sine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION： Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate

关键词： c-Fos Cyclin DI GSK-3 Cell growth, Cell cycle Hepatoma Epidermal growth factor

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Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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Journal of Sport and Health Science 2024年第3期13卷 409-418页

作者： Jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes mikael Croyal Bertrand Perret Sophie Guyonnet Bruno Vellas Laurent O.martinez Philipe de Souto Barreto For the mAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France centre d'Epidémiologie et de recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France Service de Biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France BioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy ***1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains ***,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP *** examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these ***:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the multidomain Alzheimer Prevention Trial study were ***1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year *** linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 *** analyses were conducted to examine whether apoA-I mediated these *** linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in ***:multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly med

关键词： Aging Apolipoprotein Bioenergetics Exerkine mitochondria

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Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy

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World Journal of Gastroenterology 2016年第42期22卷 9378-9386页

作者： Jean-Florian Guion-Dusserre Aurélie Bertaut Fran?ois Ghiringhelli Julie Vincent Valérie Quipourt Sophie marilier Zoé Tharin Leila Bengrine-Lefevre department of medical Oncology Centre Georges-Fran?ois Leclerc Institut National de la Santé et de la recherche médicale University of Burgundy

AIm To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic *** This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin(85 mg/m2 in over 120 min) followed by leucovorin(400 mg/m2 in over 120 min), with the addition, after 30 min of irinotecan(180 mg/m2 in over 90 min) then 5 fluorouracil(5FU)(400 mg/m2 administred intravenous bolus), followed by 5FU(2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient *** Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index most frequent severe toxicities were neutropenia(17 patients, n = 32.7%) and diarrhea(35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients(75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients(48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo(95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric pa

关键词： Elderly patients Feasibility treatment Pancreatic cancer Colorectal cancer FOLFIRINOX

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FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2015年第7期21卷 2096-2101页

作者： Jean-Florian Guion-Dusserre Veronique Lorgis Julie Vincent Leila Bengrine Francois Ghiringhelli department of medical Oncology Centre Georges-Fran?ois Leclerc Institut National de la Santé et de la recherche médicale University of Burgundy

AIm:To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic ***:Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory tofirst-line therapy consisting of gemcitabine plus oxaliplatinbased first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI[irinotecan(180 mg/m2 *** 90 min)concurrently with folinic acid(400 mg/m2 *** 120 min)followed by fluorouracil(400 mg/m2 ***)then fluorouracil 2400 mg/m2 intravenous infusion over 46 h]and bevacizumab(5mg/kg)every 2 *** response was evaluated by computed tomography scan every 4 ***:The best tumor responses using response evaluation criteria in solid tumor criteria were:complete response for 1 patient,partial response for 4 patients,and stable disease for 6 patients after 6 mo of *** response rate was 38.4%(95%CI:12.5-89)and the disease control rate was 84.5%(95%CI:42-100).Seven deaths occurred at the time of analysis,progression free survival was 8 mo(95%CI:7-16),and median overall survival was 20 mo(95%CI:8-48).No grade 4toxic events were *** grade 3 hematological toxicities and one grade 3 digestive toxicity *** adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity,and a delay in chemotherapy cycles was required for 3 ***:FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.

关键词： Biliary tract cancer Intrahepatic cholangiocarcino

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Virtual brain twins: from basic neuroscience to clinical use

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National Science Review 2024年第5期11卷 72-86页

作者： Huifang E.Wang Paul Triebkorn martin Breyton Borana Dollomaja Jean-Didier Lemarechal Spase Petkoski Pierpaolo Sorrentino Damien depannemaecker meysam Hashemi Viktor K.Jirsa Aix marseille Université Institut National de la Santéet de la Recherche Médicale Institut de Neurosciences des Systèmes(INS) UMR1106 Service de Pharmacologie Clinique et Pharmacosurveillance AP–HM

Virtual brain twins are personalized, generative and adaptive brain models based on data from an individual's brain for scientific and clinical use. After a description of the key elements of virtual brain twins,we present the standard model for personalized whole-brain network models. The personalization is accomplished using a subject's brain imaging data by three means:(1) assemble cortical and subcortical areas in the subject-specific brain space;(2) directly map connectivity into the brain models, which can be generalized to other parameters; and(3) estimate relevant parameters through model inversion, typically using probabilistic machine learning. We present the use of personalized whole-brain network models in healthy ageing and five clinical diseases: epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and psychiatric disorders. Specifically, we introduce spatial masks for relevant parameters and demonstrate their use based on the physiological and pathophysiological hypotheses. Finally, we pinpoint the key challenges and future directions.

关键词： virtual brain twin personalized modeling inference neuroscience brain disorder

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Ecto-F_1-ATPase: A moonlighting protein complex and an unexpected apoA-I receptor

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World Journal of Gastroenterology 2010年第47期16卷 5925-5935页

作者： Pierre Vantourout Claudia Radojkovic Laeticia Lichtenstein Véronique Pons Eric Champagne Laurent O martinez Institut national de la santé et de la recherche médicale U1048 Institute of metabolic and Cardiovascular Diseases Université Toulouse III Paul-Sabatier

mitochondrial ATP synthase has been recently detected at the surface of different cell types, where it is a high affinity receptor for apoA-I, the major protein component in high density lipoproteins (HDL). Cell surface ATP synthase (namely ecto-F1-ATPase) expression is related to different biological effects, such as regulation of HDL uptake by hepatocytes, endothelial cell proliferation or antitumor activity of Vγ9/Vδ2 T lymphocytes. This paper reviews the recently discovered functions and regulations of ecto-F1-ATPase. Particularly, the role of the F1-ATPase pathway(s) in HDL-cholesterol uptake and apoA-Imediated endothelial protection suggests its potential importance in reverse cholesterol transport and its regulation might represent a potential therapeutic target for HDL-related therapy for cardiovascular diseases. Therefore, it is timely for us to better understand how this ecto-enzyme and downstream pathways are regulated and to develop pharmacologic interventions.

关键词： F1Fo ATP synthase High density lipoproteins receptor Apolipoprotein A-I Purinergic receptor P2Y13 Adenylate kinase Nucleotide Endothelium Antitumor immunity

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measurement of electrical charges carried by airborne bacteria laboratory-generated using a single-pass bubbling aerosolizer

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Particuology 2015年第1期13卷 179-185页

作者： Xavier Simon Sébastien Bau denis Bémer Philippe Duquenne Institut National de recherche et de Securite(INRS)

Widely used bioaerosol generators like Collison nebulizer probably produce electrostatically charged par- ticles, but the electrical charges carried by laboratory-generated airborne microorganisms using bubbling aerosolizers are poorly understood. In this study, we measured the fraction of neutral particles and num- ber of elementary charges per particle as a function of the aerodynamic diameter of airborne bacteria （Escherichia coli and Enterococcus hirae）. Bioaerosols were produced by a liquid sparging aerosolizer-type bubbling generator, with particle sizes ranging from roughly 0.6 to 2 p^m. The experimental setup included an electrostatic precipitator and real-time devices including an electrometer, aerodynamic particle sizer, and electrical low-pressure impactor. Experimental results obtained for various operating conditions showed that aerosols produced with a higher bubbling airflow contained a larger proportion of neutral particles （from around 30% to 50%） and that bacteria carried a greater average absolute number of elementary charges （from around -10 to -60 elementary units） than those under lower airflow. Under the investigated conditions, a neutralization step is unnecessary because it may have a negative effect on the viability of sensitive microorganisms. Our results suggest that the neutral fraction can be used down- stream of an electrostatic precipitator, and that this setup may have advantages over bipolar neutralizers.

关键词： Bubbling generator Bioaerosol Electrical charge Electrostatic precipitator Escherichia coil Enterococcus hirae

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