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Inflammasome activation under high cholesterol load triggers a protective microglial phenotype while promoting neuronal pyroptosis

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Translational Neurodegeneration 2023年第1期12卷 722-744页

作者： Cristina de Dios Xenia Abadin Vicente Roca-Agujetas Marina Jimenez-Martinez Albert Morales ramon trullas Montserrat Mari Anna Colell Department of Cell Death and Proliferation Institut d’Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas(CSIC)Institut d’Investigacions Biomèdiques August Pi I Sunyer(IDIBAPS)BarcelonaSpain Centro de Investigación Biomédica en Red Sobre Enferme-dades Neurodegenerativas(CIBERNED) MadridSpain Department of Biomedicine Faculty of MedicineUniversitat de BarcelonaBarcelonaSpain Present Address:Department of Biochemistry and Molecular Biology Faculty of PharmacyUniversidad de Sevilla.Instituto de Biomedicina de Sevilla(IBiS)-Hospital Universitario Virgen del Rocío/CSICSevilleSpain Present Address:Department of Clinical Immunology and Rheumatology Amsterdam UMCAmsterdamNetherlands

Background Persistent inflammatory response in the brain can lead to tissue damage and *** Alzheimer’s disease(AD),there is an aberrant activation of inflammasomes,molecular platforms that drive inflammation through caspase-1-mediated proteolytic cleavage of proinflammatory cytokines and gasdermin D(GSDMD),the executor of ***,the mechanisms underlying the sustained activation of inflammasomes in AD are largely *** have previously shown that high brain cholesterol levels promote amyloid-β(Aβ)accumulation and oxidative ***,we investigate whether these cholesterol-mediated changes may regulate the inflam-masome *** SIM-A9 microglia and SH-SY5Y neuroblastoma cells were cholesterol-enriched using a water-soluble cholesterol *** exposure to lipopolysaccharide(LPS)plus muramyl dipeptide or Aβ,activation of the inflammasome pathway was analyzed by immunofluorescence,ELISA and immunoblotting ***-labeled Aβwas employed to monitor changes in microglia *** medium was used to study how microglia-neuron interrelationship modulates the inflammasome-mediated *** In activated microglia,cholesterol enrichment promoted the release of encapsulated IL-1βaccompanied by a switch to a more neuroprotective phenotype,with increased phagocytic capacity and release of neurotrophic *** contrast,in SH-SY5Y cells,high cholesterol levels stimulated inflammasome assembly triggered by both bacterial toxins and Aβpeptides,resulting in GSDMD-mediated ***(GSH)ethyl ester treatment,which recovered the cholesterol-mediated depletion of mitochondrial GSH levels,significantly reduced the Aβ-induced oxidative stress in the neuronal cells,resulting in lower inflammasome activation and cell ***,using conditioned media,we showed that neuronal pyroptosis affects the function of the cholesterol-enriched microglia,lowering its phagocytic activity and,the

关键词： Neuroinflammation Mitochondrial oxidative stress Phagocytosis Alzheimer’s disease DAM signature NLRP3

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Behavioral thermoregulation is highly repeatable and unaffected by digestive status in Agama atra

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Integrative Zoology 2018年第4期13卷 482-493页

作者： Jenna Van BERKEL Susana CLUSELLA-trullas Centre for Invasion Biology Department of Botany and ZoologyStellenbosch UniversityMatielandSouth Africa

The precision and the extent of behavioral thermoregulation are likely to provide fitness benefits to *** the factors driving variation in selected or preferred body temperature(T_(set))and its usefulness as a proxy for optimal physiological temperature(Topt)are still *** T_(set)is often conserved among closely related species,substantial variation at the individual,population and species level has also been ***,the repeatability(calculated as the intra-class correlation coefficient)of T_(set)is generally *** factor that influences T_(set)is feeding status,with fed reptiles typically showing higher T_(set),a process thought to aid meal ***,using experiments simulating realistic feeding and fasting regimes in Agama atra,a heliothermic lizard from southern Africa,we test if T_(set)and its repeatability under these 2 states significantly *** T_(set)ranged from 33.7 to 38.4℃,with a mean(±SE)of 36.7±0.1℃ for fed and 36.6±0.1℃ for unfed *** of repeatability showed that females tend to be more consistent in the selection of body temperature than males,but not significantly so regardless of feeding *** report some of the highest repeatability estimates of T_(set)to date(full range:0.229–0.642),and that the weak positive effects of feeding status on T_(set)did not increase its *** conclusion,one of the major prerequisites for natural selection,consistent among-individual variation,is present,making the adaptive significance of T_(set)considerably more plausible.

关键词： climate change co-adaptation evolutionary potential inter-individual variation specific dynamic action thermal preference

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《未来的光防护:挑战与机遇》共识解读:国际防晒化妆品发展趋势及对中国的启示

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中华皮肤科杂志 2020年第12期53卷 962-966页

作者：赖维郑跃 Granger Corinne trullas Carles Krutmann Jean 刘玮中山大学附属第三医院皮肤科广州510630 Innovation and Development ISDIN 08000 BarcelonaSpain IUF-Leibniz Research Institute for Environmental Medicine 40210 DüsseldorfGermany 解放军空军特色医疗中心皮肤科北京100036

目前对防晒化妆品的认识还存在一些误区,如防晒系数越高越好,防晒剂可以引起使用者缺钙等。防晒化妆品也存在诸如防晒系数测定和标识方法不统一、防护波长范围不足、对人体及环境的安全性不明等许多问题和挑战。本文阐述国际上防晒化妆... 详细信息

目前对防晒化妆品的认识还存在一些误区,如防晒系数越高越好,防晒剂可以引起使用者缺钙等。防晒化妆品也存在诸如防晒系数测定和标识方法不统一、防护波长范围不足、对人体及环境的安全性不明等许多问题和挑战。本文阐述国际上防晒化妆品面临的问题、发展趋势及对中国防晒化妆品研发的启示等,供临床医师参考。

关键词：防晒剂防晒系数毒性作用趋势

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