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Redox regulation of the immune response

Cellular & Molecular Immunology 2022年第10期19卷 1079-1101页

作者： gerwyn morris Maria Gevezova Victoria Sarafian Michael Maes Deakin University IMPACT-the Institute for Mental and Physical Health and Clinical TranslationSchool of MedicineBarwon HealthGeelongVICAustralia Department of Medical Biology Medical University-PlovdivPlovdivBulgaria Research Institute at Medical University-Plovdiv PlovdivBulgaria Department of Psychiatry Faculty of MedicineKing Chulalongkorn Memorial HospitalBangkokThailand Department of Psychiatry Medical University of PlovdivPlovdivBulgaria

The immune-inflammatory response is associated with increased nitro-oxidative stress.The aim of this mechanistic review is to examine:(a)the role of redox-sensitive transcription factors and enzymes,ROS/RNS production,and the activity of cellular antioxidants in the activation and performance of macrophages,dendritic cells,neutrophils,T-cells,B-cells,and natural killer cells;(b)the involvement of high-density lipoprotein(HDL),apolipoprotein A1(ApoA1),paraoxonase-1(PON1),and oxidized phospholipids in regulating the immune response;and(c)the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response.The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB,HIF1α,the mechanistic target of rapamycin,the phosphatidylinositol 3-kinase/protein kinase B signaling pathway,mitogen-activated protein kinases,5'AMP-activated protein kinase,and peroxisome proliferator-activated receptor.The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS.They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems,nuclear factor erythroid 2-related factor 2,and the HDL/ApoA1/PON1 complex.Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems,the tricarboxylic acid cycle,mitochondrial functions,and the metabolism of immune cells.In conclusion,redox-associated mechanisms modulate metabolic reprogramming of immune cells,macrophage and T helper cell polarization,phagocytosis,production of pro-versus anti-inflammatory cytokines,immune training and tolerance,chemotaxis,pathogen sensing,antiviral and antibacterial effects,Toll-like receptor activity,and endotoxin tolerance.

关键词： Oxidative and nitrosative stress Immune response Inflammation Antioxidants Physiological stres

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Potential therapeutic interventions based on the role of the endoplasmic reticulum stress response in progressive neurodegenerative diseases

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Neural Regeneration Research 2018年第11期13卷 1887-1889页

作者： Basant K.Puri gerwyn morris Department of Medicine Imperial College LondonHammersmith Hospital IMPACT Strategic Research Centre School of MedicineDeakin University

In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed：＇a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains of＂vesicles＂＇（Porter et al.,1945）.This constituted the first published observation of the endoplasmic reticulum（ER）and,while it was not evident at that time,this cytoplasmic system of interconnecting membrane-lined channels, comprising vesicles, tubules and cisternae, has numerous important functions.

关键词： Potential therapeutic interventions based on the role of the endoplasmic reticulum stress response in progressive neurodegenerative diseases UPR NAC

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Indirect contact matters:Mid-flight external trunk perturbation increased unilateral anterior cruciate ligament loading variables during jump-landings

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Journal of Sport and Health Science 2023年第4期12卷 534-543,F0003页

作者： Yu Song Ling Li Jacob Layer Raychl Fairbanks Maddy Jenkins gerwyn Hughes Derek Smith Margaret Wilson Qin Zhu Boyi Dai Division of Kinesiology and Health University of WyomingLaramieWY 82071USA Department of Kinesiology University of San FranciscoSan FranciscoCA 94117USA Department of Theatre and Dance University of WyomingLaramieWY 82071USA

Purpose:To determine the effect of unanticipated mid-flight medial-lateral external perturbation of the upper or lower trunk on anterior cruciate ligament(ACL)loading variable s during jump-landings.Methods:Thirty-two participants performed double-leg vertical jump-landings while bilateral kinematics and kinetics were collected under 6conditions(upper or lower trunk perturbation locations;no,left,or right perturbation directions).Two customized catapult apparatuses were created to apply pushing perturbation to participants near the maximal jump height.Results:The ball contacted participants near the center of mass for the lower-trunk conditions and approximately 23 cm above the center of mass for the upper-trunk conditions.Under upper-trunk perturbation,the contralateral leg demonstrated significantly smaller knee flexion angles at initial contact and greater peak knee abduction angles,peak vertical ground reaction forces,peak knee extension moments,and peak knee adduction moments compared to other legs among all conditions.Under lower-trunk perturbation,the contralateral leg showed significantly smaller knee flexion angles at initial contact and increased peak vertical ground reaction forces and peak knee extension moments compared to legs in the no-perturbation conditions.Conclusion:Mid-flight external trunk pushing perturbation increased ACL loading variables for the leg contralateral to the perturbation.The uppertrunk perturbation resulted in greater changes in ACL loading variables compared to the lower-trunk perturbation,likely due to trunk and ipsilateral leg rotation and more laterally located center of mass relative to the contralateral leg.These findings may help us understand the mechanisms of indirect-contact ACL injuries and develop jump-landing training strategies under mid-flight trunk perturbation to better prevent ACL injury.

关键词： ACL injuries Biomechanics Kinematics Kinetics Landing

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Development ofα-synuclein as a potential molecular marker for Parkinson's Disease

Development ofα-synuclein as a potential molecular marker f...

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2011全国老年痴呆与衰老相关疾病学术会议第三届山东省...

作者： Penelope Foulds gerwyn Green Peter Diggle David M.A.Mann J.Douglas Mitchell David Allsop Division of Biomedical and Life Sciences Lancaster University Division of Medicine School of Health and Medicine Lancaster University Neurodegeneration and Mental Health Research Group University of Manchester Hope Hospital Salford M6 8HD UK

Objectives:We aim to use immunoassay methods for the measurement of total and soluble oligomeric forms of alpha-synuclein(a-syn),and phosphorylated a-syn(pS-a-syn) in;a) longitudinal blood plasma samples,and b) post-mortem cerebral spinal fluid(CSF). Background:Parkinson s disease(PD) is characterised pathologically by selective loss of dopaminergic neurones from the substantia nigra,and the presence of Lewy bodies in surviving cells.The major protein

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