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Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

Journal of Molecular Cell Biology 2020年第3期12卷 202-215页

作者： Augustin Le Naour Melissa Prat Benolt Thibault Renaud Mével Léa Lemaitre Helene Leray Marie-Veronique Joubert Kimberley Coulson Muriel Golzio Lise Lefevre Eliane Mery Alejandra Martinez Gwénael Ferron Jean-Pierre Delord agnès coste Bettina Couderc Institut Claudius Regaud-IUCT Oncopole Universite de ToulouseToulouseFrance INsERM UMR 1037 Cancer Research Center of Toulouse(CRCT)ToulouseFrance UMR 152 Pharma Dev Universite de ToulouseIRDUPSToulouseFrance UMR CNRs 5089 Institut de Pharmacologie et de Biologie Structurale(IPBS)ToulouseFrance

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MsCs)are involved in tumor progression and *** this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MsCs)can acquire a CA-MsCs *** tumor cells trigger the transformation of MsCs to CA-MsCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor ***,through their released factors,CA-MsCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor *** CXCR1/2 receptors are inhibited,these CA-MsC-activated macrophages lose their M2 properties and acquire an anti-tumoral *** ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of *** high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

关键词： chemoresistance macrophages mesenchymal stromal cells ovarian adenocarcinoma chemokines

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Genotypic,size and morphological diversity of virioplankton in a deep oligomesotrophic freshwater lake(Lac Pavin,France)

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Journal of Environmental sciences 2017年第3期29卷 48-59页

作者： Jonathan Colombet agnès Robin Télesphore sime-Ngando Laboratory Microorganisms:Oenome and Environment Clermont University Blaise PascalUMR CNRS 602324 avenue des LandaisBP 80026F-63171 AubiereFrance CIRAD UMR Eco&Sols2 place Viala34060 Montpellier Cedex 1France

We examined changes in morphological and genomic diversities of viruses by means of transmission electronic microscopy and pulsed field gel electrophoresis （PFGE） over a nine-month period （April-December 2005） at four different depths in the oligomesotrophic Lac Pavin. We found that the majority of viruses in this lake belonged to the family of siphouiridae or were untailed, with capsid sizes ranging from 30 to 60 nm, and exhibited genome sizes ranging from 15 to 45 kb. On average, 12 different genotypes dominated each of the PFGE fingerprints. The highest genomic viral richness was recorded in summer （mean = 14 bands per PFGE fingerprint） and in the epilimnion （mean = 13 bands per PFGE fingerprint）. Among the physico-chemical and biological variables considered, the availability of the hosts appeared to be the main factor regulating the variations in the viral diversity.

关键词： VirusLac PavinDynamicMorphological diversity Genomic diversity

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Revisiting cerebral endothelial cells in Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2911-2912页

作者： Amira s.Hanafy Department of Neurosurgery University Hospital BonnBonnGermany

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory *** only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the *** amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

关键词： Alzheimer Aβ cerebral

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A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience Center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged froms transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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Micro-alloying of Zn and Ca in vacuum induction casted bioresorbable Mg system:Perspectives on corrosion resistance,cytocompatibility,and inflammatory response

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Journal of Magnesium and Alloys 2024年第7期12卷 2812-2825页

作者： Manisha Behera agnès Denys Rajashekhara shabadi Fabrice Allain Cosmin Gruescu UnitéMatériaux et Transformations(UMET) Universitéde LilleCNRSINRAENSCLUMR 8207UMETF-59000 LilleFrance Universitéde Lille CNRSUMR 8576-UGSF-Unitéde Glycobiologie Structurale et FonctionnelleF-59000 LilleFrance

There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic *** is driven by their potential to address challenges like stress shielding and the need for secondary removal *** this study,biodegradable magnesium alloys were produced using the Vacuum Induction Casting *** impact of micro-alloying Zn and Ca in Mg-xZn-0.2Ca(x=0.1,0.2,0.3,and 0.4 wt%)alloys on corrosion resistance,cytocompatibility,and early-stage inflammatory response was *** and sEM-EDs analysis confirmed the presence of Ca_(2)Mg_(6)Zn_(3)secondary phases in all *** Mg-0.3Zn-0.2Ca alloy exhibited the lowest corrosion rate and an elastic modulus of 36.8 GPa,resembling that of natural *** measurements indicated a correlation between grain size and secondary phase volume fraction in explaining corrosion *** vitro degradation in simulated body fluid(sBF)for 21 days showed hydroxyapatite formation on alloy surfaces,aligning with electrochemical *** vitro cytotoxicity tests demonstrated the cytocompatibility of all alloys,with Mg-0.3Zn-0.2Ca having the highest cell viability over a 6-day cell *** into the inflammatory response with RAW-Blue macrophages revealed the anti-inflammatory properties of Mg-0.3Zn-0.2Ca ***-alloying with 0.3 wt%Zn and 0.2 wt%Ca enhanced mechanical properties,corrosion resistance,cytocompatibility,and immunomodulatory *** positions the Mg-0.3Zn-0.2Ca alloy as a promising biodegradable implant for bone fixation applications.

关键词： Micro-alloying MgZnCa Corrosion resistance In vitro Anti-inflammatory response

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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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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Natural stilbenes effects in animal models of Alzheimer’s disease

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Neural Regeneration Research 2020年第5期15卷 843-849页

作者： Aline Freyssin Guylène Page Bernard Fauconneau agnès Rioux Bilan University of Poitiers EA3808 NEUVACOD (Neurovascular Unit and Cognitive Disorders)P?le Biologie Santé

Alzheimer’s disease is one of the most frequent neurodegenerative *** pathology is characterized by protein aggregates,mainly constituted by amyloid peptide and tau,leading to neuronal death and cognitive *** currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic ***,stilbenes presenting multiple pharmacological effects could be good potential therapeutic *** aim of this review is to gather the more significant papers among the broad literature on this topic,concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer’s ***,numerous studies focus on cellular models,but an in vivo approach remains of primary importance since in animals (mice or rats,generally),bioavailability and metabolism are taken into account,which is not the case in in vitro ***,examination of memory ability is feasible in animal models,which strengthens the relevance of a compound with a view to future therapy in *** paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in *** review shows that resveratrol,the reference polyphenol,is largely studied and seems to have interesting properties on amyloid plaques,and cognitive ***,some resveratrol derivatives such as gnetin C,trans-piceid,or astringin have never been tested on ***,pterostilbene is of particular interest,by its improvement of cognitive disorders and its neuroprotective *** could be relevant to evaluate this molecule in clinical trials.

关键词： Alzheimer's disease amyloid animal models cognitive impairment inflammation natural stilbenes neuroprotection resveratrol tau

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Temporal Behaviour of a Corner separation in a Radial Vaned Diffuser of a Centrifugal Compressor Operating near surge

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Journal of Thermal science 2013年第6期22卷 555-564页

作者： A.Marsan I.Trébinjac s.coste G.Leroy Laboratoire de Mécanique des Fluides et d'Acoustique UMR CNRS 5509 cole Centrale de Lyon Turbomeca Safran group

The temporal behaviour of a flow separation in the hub-suction side comer of a transonic diffuser is studied thanks to unsteady numerical simulations based on the phase-lagged approach. The validity of the numerical re- sults is confn＇med by comparison with experimental unsteady pressure measurements. An analysis of the instan- taneous skin-friction pattern and particles trajectories is presented. It highlights the topology of the separation and its temporal behaviour. The major result is that, despite of a highly time-dependent core flow, the separation is found to be a ＂fixed unsteady separation＂ characterized by a fixed location of the main saddle of the separation but an extent of the stall region modulated by the pressure waves induced by the impeller-diffuser interaction.

关键词： Corner separation Radial Vaned Diffuser Centrifugal Compressor surge

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Complementary roles of glial cells in generating region-specific neuroinflammatory responses and phagocytosis in Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2917-2918页

作者： Leyre Ayerra Maria s.Aymerich Universidad de Navarra Facultad de CienciasDepartamento de Bioquímica y GenéticaPamplonaSpain CIMA-Universidad de Navarra PamplonaSpain IdisNA Instituto de Investigación Sanitaria de NavarraPamplonaSpain

Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic *** has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be *** leukocyte antigen.

关键词： inflammation leukocyte generating

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