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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of physiology and Pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Dynamics of Primary Events in the Photocycle of Excited Bacteriorhodopsin

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Acta Biochimica et Biophysica Sinica 2004年第11期36卷 724-728页

作者： Jun-Jun LU, Ming MING, Yi YANG, Jia WU, Bo LI, Jian-Dong DING, Qing-Guo LI, and Shi-Xiong QIANdepartment of Physics, Fudan University, Shanghai 200433, China department of Macromolecular Science, Key Laboratory of molecular Engineering of Polymers, Fudan University, Shanghai 200433, China department of physiology and biophysics, School of Life Sciences, Fudan University, Shanghai 200433, China department of Physics Fudan UniversityShanghai 200433 China department of Macromolecular Science Key Laboratory of Molecular Engineering of Polymers Fudan UniversityShanghai 200433 China department of physiology and biophysics School of Life Sciences Fudan UniversityShanghai 200433 China

Transient dynamic behavior of the excited bacteriorhodopsin (BR), which was isolated from the strain H. salinarum, was studied at excitation wavelength from 585 to 639 nm. With the one-color femtosecond (fs) pump-probe technique, we revealed the primary events in BR's photocycle that took place in an ultrafast time scale. From the analysis of the decay components of the dynamical traces, it was evident that the isomerization of the retinal

关键词： bacteriorhodopsin transient dynamics primary events femtosecond laser pump-probe technique

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Post-translational regulation of inflammasomes

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Cellular & molecular Immunology 2017年第1期14卷 65-79页

作者： Jie Yang Zhonghua Liu Tsan Sam Xiao department of Pathology Case Western Reserve University Cleveland OH 44106-7288 USA Graduate Program in physiology and biophysics Department of Physiology and Biophysics Case Western Reserve University Cleveland OH 44106-7288 USA

Infiammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications （PTMs） that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions.

关键词： inflammasome phosphorylation post-translational modifications ubiquitination

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A remembrance of Professor TP FENG

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生理学报 2007年第6期59卷 713-715页

作者： Richard W.Tsien department of molecular and Cellular physiology Stanford University

It is both an honor and pleasure to be given this opportunity to remember Professor TP FENG and his many *** made many important scientific discoveries,labored mightily to establish firmly physiology and Neuroscience in China,and was a major force in setting a high standard for scientific *** is safe to say that the past and future of Neuroscience in China would be very different had Professor FENG not provided leadership,by dint of organization,persuasion and strong personal example.

关键词：神经系统科学中国冯德培生理学院士科研教学

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Pathophysiology of alcoholic pancreatitis:An overview

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World Journal of Gastroenterology 2006年第46期12卷 7421-7427页

作者： Parimal Chowdhury Priya Gupta department of physiology and biophysics University of Arkansas for Medical sciences Little Rock Arkansas United States

Use of alcohol is a worldwide habit regardless of socio- economic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

关键词： Alcohol Metabolism Pancreatic function Pancreatitis Mechanism of action

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Involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity

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World Journal of Gastroenterology 2006年第5期12卷 796-799页

作者： Byung Joo Kim Jae Yeoul Jun Insuk So Ki Whan Kim department of physiology and biophysics College of MedicineSeoul National UniversityRepublic of Korea department of physiology College of MedicineChosun UniversityRepublic of Korea

AIM： Interstitial cells of Cajal （ICCs） are the pacemaker cells that generate slow waves in the gastrointestinal （GI） tract. We have aimed to investigate the involvement of mitochondrial Na^＋-Ca^2＋ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal. METHODS： Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents （voltage clamp） and potentials （current clamp） from cultured ICCs. RESULTS： Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 μmol/L and CGP37157 from 10 to 30 μmol/L effectively inhibited Ca^2＋ efflux from mitochondria in pacemaking activity of ICCs. The ICsos of clonazepam and CGP37157 were 37.1 and 18.2 μmol/ L, respectively. The addition of 20 μmol/L NiCl2 to the internal solution caused a ＂wax and wane＂ phenomenon of pacemaking activity of ICCs. CONCLUSION： These results suggest that mitochondria Na^＋-Ca^2＋ exchange has an important role in intestina pacemaking activity.

关键词： Mitochondrial Na^+-Ca^2+ exchange Interstitial cells of Cajal

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Impact of liver diseases on the development of type 2 diabetes mellitus

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World Journal of Gastroenterology 2011年第48期17卷 5240-5245页

作者： Po-Shiuan Hsieh Yen-Ju Hsieh department of physiology and biophysics National Defense Medical Center department of Medical Research Tri-Service General Hospital

The prevalence of type 2 diabetes mellitus （T2DM） is higher in patients who have liver diseases such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease and cirrhosis. It is suggested that there is a pathogenic link between the presence of T2DM and the severity of liver injury. However, evidence related to the impact of hepatic inflammation on the development of T2DM has not yet emerged. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases, the impact of liver diseases on insulin resistance and 13 cell dysfunction, and the potential mechanisms whereby coexistent liver diseases exacerbate the development of T2DM.

关键词： Hepatic inflammation Insulin resistance βcell dysfunction Type 2 diabetes mellitus

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Dynamic change of Adamalysin 19 (ADAM19) in human placentas and its effects on cell invasion and adhesion in human trophoblastic cells

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Science China(Life Sciences) 2009年第8期52卷 710-718页

作者： SANG QingXiang Amy department of Chemistry and Biochemistry and Institute of molecular biophysics Florida State University

Human ADAM19 is a recently identified member of the ADAM *** is highly expressed in human placentas,but its dynamic change and function at the human feto-maternal interface during placentation remain to be *** this present study,the spatial and temporal expression and cellular localization of ADAM19 in normal human placentas were first demonstrated,and the effects of ADAM19 on trophoblast cell adhesion and invasion were further investigated by using a human choriocarcinoma cell line(JEG-3) as an in vitro *** data demonstrated that ADAM19 was widely distributed in villous cytotrophoblast cells,syncytiotrophoblast cells,column trophoblasts,and villous capillary endothelial cells during early *** mRNA and protein level of ADAM19 in placentas was high at gestational weeks 8-9,but diminished significantly at mid-and term *** JEG-3 cells,the overexpression of ADAM19 led to diminished cell invasion,as well as increases in cell adhesiveness and the expression of E-cadherin,with no changes in β-catenin expression *** data indicate that ADAM19 may participate in the coordinated regulation of human trophoblast cell behaviors during the process of placentation.

关键词： ADAM19 human trophoblast cells invasion adhesion

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molecular dynamics simulations of membrane deformation induced by amphiphilic helices of Epsin,Sar1p,and Arf1

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Chinese Physics B 2018年第3期27卷 544-550页

作者： Zhen-Lu Li department of physiology and biophysics Case Western Reserve UniversityCleveland 44106USA department of Physics Nanjing UniversityNanjing 210093China

The N-terminal amphiphilic helices of proteins Epsin,Sarlp,and Arfl play a critical role in initiating membrane *** interactions of these amphiphilic helices with the lipid membranes are investigated in this study by combining the all-atom and coarse-grained *** the all-atom simulations,the amphiphilic helices of Epsin and Sarlp are found to have a shallower insertion depth into the membrane than the amphiphilic helix of Arfl,but remarkably,the amphiphilic helices of Epsin and Sat lp induce higher asymmetry in the lipid packing between the two monolayers of the *** insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distributions of polar and non-polar residues along the *** directly compare their ability to deform the membrane,the coarse-grained simulations are performed to investigate the membrane deformation under the insertion of multiple helices.

关键词： cell membrane amphiphilic helix membrane deformation molecular simulation

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LIVE IMAGING OF EARLY DEVELOPMENTAL PROCESSES IN MAMMALIAN EMBRYOS WITH OPTICAL COHERENCE TOMOGRAPHY

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Journal of Innovative Optical Health Sciences 2009年第3期2卷 253-259页

作者： KIRILL V.LARIN IRINA V.LARINA MICHAEL LIEBLING MARY E.DICKINSON department of Biomedical Engineering University of Houston HoustonTXUSA department of molecular physiology and biophysics Baylor College of Medicine HoustonTXUSA department of Electrical and Computer Engineering University of California Santa BarbaraCAUSA

Early embryonic imaging of cardiovascular development in mammalian models requires a methodthat can penetrate through and distinguish the many tissue layers with high spatial and temporalresolution. In this paper we evaluate the capability of Optical Coherence Tomography (OCT)technique for structural 3D embryonic imaging in mouse embryos at different stages of thedevelopmental process ranging from 7.5 dpc up to 10.5 dpc. Obtained results suggest that thecollected data is suitable for quantitative and qualitative measurements to assess cardiovascularfunction in mouse models, which is likely to expand our knowledge of the complexity of theembryonic heart, and its development into an adult heart.

关键词： Optical Coherence Tomography non-invasive mouse embryos cardiovascular function.

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