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Endocannabinoid control of neuroinflammation in traumatic brain injury by monoacylglycerol lipase in astrocytes

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Neural Regeneration Research 2023年第5期18卷 1023-1024页

作者： Chu Chen Department of Cellular and Integrative Physiology Long School of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA

Traumatic brain injury(TBI)is a temporary or permanent disruption of brain function caused by external forces.TBI has been recognized as an important risk factor for the development of Alzheimer’s disease and dementia later in life.However,the mechanisms by which TBI contributes to developing Alzheimer’s disease are largely unknown.

关键词： inflammation Alzheimer TBI

TDP-43 is a key molecule accelerating development of Alzheimer’s disease following traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 955-956页

作者： Chu Chen Department of Cellular and Integrative Physiology Long School of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA

Currently,more than 55 million people have dementia worldwide and Alzheimer’s disease(AD)is one of the most common causes of dementia in aging.However,no effective therapies are currently available for the prevention and treatment of AD.This is largely due to our limited understanding of the mechanisms underlying the neuropathogenesis of AD.It has widely been recognized that AD is heterogeneous and that multi-factors are contributing to the pathogenesis of AD.Accumulated evidence suggests that traumatic brain injury(TBI)is an important risk factor for the development of AD and dementia later in life(Guo et al.,2000;Johnson et al.,2010).However,the precise mechanism by which TBI contributes to developing AD has yet to be elucidated.

关键词： Alzheimer traumatic

Pathology-induced NG2 proteoglycan expression in microglia

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Neural Regeneration Research 2023年第4期18卷 801-802页

作者： Erika Meyer Anja Scheller Molecular physiology Center for Integrative Physiology and Molecular MedicineUniversity of SaarlandHomburgGermany(Meyer EScheller A)Laboratory of Brain Ischemia and NeuroprotectionDepartment of Pharmacology and TherapeuticsState University of MaringáMaringáBrazil

Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different functions.At a first glance,they appear not to share many cellular properties,nor are directly related to one another or derived from a common ancestor.Despite all differences,emerging data show that both cell types express the protein nerve/glial antigen 2(NG2)after pathological insults(Figure 1).For years,it remained controversial whether microglia really could express NG2 upon injury,with contradictory results reported among different disease models.Addressing this question,we could recently show by using triple transgenic knock-in mice and either an acute injury model(stab wound injury)or the middle cerebral artery occlusion combined with immunohistochemistry that a subset of microglia activates the cspg4 gene in a disease dependent manner leading to a bonafide microglia-specific NG2 protein expression besides OPCs and pericytes.Our data show that the cspg4 gene not only gets transcribed in microglia based on reporter expression after recombination,but also the protein itself is expressed(Huang et al.,2020).

关键词： NG2 wound Figure

Elevated L-lactate Promotes Major cellular Pathologies Associated with Neurodegenerative Diseases

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Neuroscience Bulletin 2021年第3期37卷 380-384页

作者： Andrew DChapp Jessica EBehnke Kyle MDriscoll Taija Hahka Zoe LaLonde Zhiying Shan Qing-Hui Chen department of Kinesiology and integrative physiology Michigan Technological UniversityHoughtonMI 49931USA department of Biological Sciences Michigan Technological UniversityHoughtonMI 49931USA

Dear Editor,Small,short-chain fatty acids(SCFAs)(acetic acid,propionic acid,and butyric acid:conjugate bases,acetate,propionate,and butyrate)as well as the alpha-hydroxy acid,L-lactic acid(conjugate base,L-lactate)are important energy substrates and signaling molecules in the central nervous system(CNS)[1,2].L-lactic acid is produced by glycolysis[3]and gut microbes[4]and is released in large quantities during exercise[5].

关键词： conjugate bases quantities

Human recombinant soluble ACE2(hrsACE2)shows promise for treating severe COVID19

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Signal Transduction and Targeted Therapy 2020年第1期5卷 303-304页

作者： Tarek Mohamed Abd El-Aziz Ahmed Al-Sabi James D.Stockand Department of Cellular and Integrative Physiology University of Texas Health Science Center at San AntonioSan AntonioTX 78229-3900USA Zoology department Faculty of ScienceMinia UniversityEl-Minia 61519Egypt College of Engineering and Technology American University of the Middle EastKuwaitKuwait

A recent study by Zoufaly et al.published in The Lancet Respiratory Medicine describes encouraging data from the first severe COVID-19 patient successfully treated with human recombinant soluble angiotensin-converting enzyme-2(hrsACE2).1 The published data document upon treatment of an adaptive immune response,the disappearance of the virus swiftly from the serum,the nasal cavity and lungs,and a reduction of inflammatory cytokine levels that are critical for COVID-19 pathology.Notably,the use of hrsACE2 did not impede the generation of neutralizing antibodies,leading to a significant clinical improvement of the treated patient.

关键词： ACE2 al cavity

Metabolic cost of level,uphill,and downhill running in highly cushioned shoes with carbon-fiber plates

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Journal of Sport and Health Science 2022年第3期11卷 303-308页

作者： Clarissa S.Whiting Wouter Hoogkamer Rodger Kram Locomotion Laboratory Department of Integrative PhysiologyUniversity of ColoradoBoulderCO 80309USA integrative Locomotion Lab Department of KinesiologyUniversity of MassachusettsAmherstMA 01003USA

Background:Compared to conventional racing shoes,Nike Vaporfly 4% running shoes reduce the metabolic cost of level treadmill running by4%.The reduction is attributed to their lightweight,highly compliant,and resilient midsole foam and a midsole-embedded curved carbon-fiber plate.We investigated whether these shoes also could reduce the metabolic cost of moderate uphill(+3°) and downhill(-3°) grades.We tested the null hypothesis that,compared to conventional racing shoes,highly cushioned shoes with carbon-fiber plates would impart the same ~4%metabolic power(W/kg) savings during uphill and downhill running as they do during level running.Methods:After familiarization,16 competitive male runners performed six 5-min trials(2 shoes × 3 grades) in 2 Nike marathon racing-shoe models(Streak 6 and Vaporfly 4%) on a level,uphill(+3°),and downhill(-3°) treadmill at 13 km/h(3.61 m/s).We measured submaximal oxygen uptake and carbon dioxide production during Minutes 4-5 and calculated metabolic power(W/kg) for each shoe model and grade combination.Results:Compared to the conventional shoes(Streak 6),the metabolic power in the Vaporfly 4% shoes was 3.83%(level),2.82%(uphill),and2.70%(downhill)less(all p <0.001).The percent of change in metabolic power for uphill running was less compared to level running(p=0.04;effect size(ES)=0.561) but was not statistically different between downhill and level running(p=0.17;ES=0.356).Conclusion:On a running course with uphill and downhill sections,the metabolic savings and hence performance enhancement provided by Vaporfly 4% shoes would likely be slightly less overall,compared to the savings on a perfectly level race course.

关键词： Energetics Incline Locomotion Oxygen consumption Running economy

p38-dependent Activation of TACE Mediates the Blockade of TNFR1/NF-κB pathway by Hydroxy-safflor Yellow A

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p38-dependent Activation of TACE Mediates the Blockade of TN...

Cavefish mount a rapid and sustained regenerative response following skeletal muscle injury

2014中国医师协会中西医结合医师大会

作者： Hai-Fang Wang Fredrick M.Pavalko Yue-Jin Yang Jin-Lian Liu Qing-wen Cao Xue-Ping Huo Ning Peng Yuan Li Jun Hu Qin-She Liu Laboratory Center of Shaanxi Province People's Hospital Department of Cellular and Integrative Physiology Indiana University School of Medicine

Background and Purpose TNF-a is implicated in the initiation of vascular inflammation.Hydroxysafflor Yellow A(HSYA) is the major active component of safflower,a Chinese herbal medicine well known for its cardiovascular protective activity.However,the effect of HSYA on TNF-a-induced activation of arterial endothelial cell(AEC) and the underlying mechanisms have not been clarified.Experimental Approach Cell adhesion assay in vitro was performed to determine the adhesion of macrophage RAW264.7 cells to AECs.Protein levels were evaluated by Western blot analysis.Cell surface level of TNFRl was determined by Flow cytometry analysis.Soluble TNFRl(sTNFRl) in cell culture media was measured by ELISA.Key Results HSYA dose-dependently suppressed up-regulation of ICAM-1 protein in TNF-a stimulated AECs.120 uM HSYA significantly inhibited the adhesion of RAW264.7 cells to AECs.HSYA inhibited TNFRl-mediated IκBα degradation in a concentration- and time-dependent manner.Moreover,HSYA reduced cell surface level of TNFRl,and meanwhile increased the content of sTNFRl in the culture media.Inhibition of TNF-a converting enzyme(TACE) by TAPI-O dose-dependently inhibited the effect of HSYA on TNFRl-mediated IκBα degradation,implying the occurrence of TACE-mediated TNFRl shedding.Furthermore,HSYA induced phosphorylation of both p38 and ERK,whereas inhibition of HSYA on TNFR1/IκBα signal was only suppressed by pre-addition of p38 blocker.Finally,HSYA-induced p38 phosphorylation was associated with a phosphorylation of TACE,suggesting a p38-dependent activation of TACE.Conclusion and Impplications HSYA suppresses TNF-a-induced activation of AECs,at least in part,through inhibiting TNFRl-mediated NF-kB pathway.p38-dependent activation of TACE may be involved in this effect of HSYA.

关键词： HSYA TNFR1 arterial endothelial cell NF-kB pathway TACE

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Zoological Research 2023年第4期44卷 776-778页

作者： Luke Olsen Huzaifa Hassan Fanning Xia Sarah Keaton Nicolas Rohner Stowers Institute for Medical Research Kansas CityMO 64110USA department of Molecular&integrative physiology University of Kansas Medical CenterKansas CityKS 66160USA department of Biological Sciences DePaul UniversityChicagoIL 60614USA

Dear Editor,Physical injury and tissue damage are prevalent throughout the animal kingdom,with the ability to regenerate quickly and efficiently providing a selective advantage.In most vertebrates,skeletal muscle possesses a remarkable ability to regenerate,making it a valuable model for investigating the cellular processes underpinning tissue regeneration.Following damage,skeletal muscle mounts a complex regenerative cascade centered around dedicated muscle stem cells,i.e.,satellite cells.These satellite cells are,in turn,regulated by both resident and infiltrating innate immune cells of myeloid lineage,which play a crucial role in activating and guiding the transition of satellite cells towards maturation(Chen et al.,2020;Tidball,2017;Tidball&Villalta,2010).While critical for muscle regeneration,the innate immune system is energetically costly,resulting in many species decreasing immune investment under nutrient-limited environments.Whether this reduced investment results in a decreased capacity to mount a regenerative response following tissue damage remains unclear.Here,we utilized an emerging evolutionary model,the Mexican tetra(Astyanax mexicanus),to investigate the consequences of shifts in immune system investment on skeletal muscle regeneration.

关键词： sustained mount injury

Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain

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Neural Regeneration Research 2019年第5期14卷 757-761页

作者： Abraam M.Yakoub department of Molecular and cellular physiology Stanford University

Multiple protocols have been devised to generate cerebral organoids that recapitulate features of the developing human brain, including the presence of a large, multi-layered, cortical-like neuronal zone. However, the central question is whether these organoids truly present mature, functional neurons and astrocytes, which may qualify the system for in-depth molecular neuroscience studies focused at neuronal and synaptic functions. Here, we demonstrate that cerebral organoids derived under optimal differentiation conditions exhibit mature, fully functional neurons and astrocytes, as validated by immunohistological, gene expression, and electrophysiological, analyses. Neurons in cerebral organoids showed gene expression profiles and electrophysiological properties similar to those reported for fetal human brain. These important findings indicate that cerebral organoids recapitulate the developing human brain and may enhance use of cerebral organoids in modeling human brain development or investigating neural deficits that underlie neurodevelopmental and neuropsychiatric conditions, such as autism or intellectual disorders.

关键词： cerebral organoids human brain stem cells neurons astrocytes neurodevelopmental disorders neuropsychiatric disorders autism