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Infection with SARS-CoV-2 can cause pancreatic impairment

Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key Laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key Laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key Laboratory of biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National Laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

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UV difference spectra and electrophoresis of recombination of lanthanides and calmodulin

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Chinese Science Bulletin 1996年第22期41卷 1905-1911页

作者：陈旭周玉祥徐育敏 State Key Laboratory of biomembrane and biomembrane Engineering Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China

The studies of the effects of lanthanides on biological system show that lanthanides(Ln3+)can facilitate growth of crops and increase their ***,Ln3+ is toxicto some animal tissues,although the reaction mechanism of Ln3+ in biological system isnot *** roles of Ln3+ in living system may be related to the competition withCa2+.Calmodulin（CaM）,an ubiquitous Ca2+-binding protein that mediates

关键词： lanthanide calmodulin UV difference spectra.

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Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons

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Acta Pharmacologica Sinica 2003年第12期24卷 74-78页

作者： ZHANG Guang-Qin, HAO Xue-Mei, CHEN Shi-Zhong~1, ZHOU Pei-Ai, CHENG He-Ping, WU Cai-Hong~2 State Key Laboratory of biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871 ~1Department of Traditional Chinese Medicine, School of Pharmaceutical Science, Peking University, Beijing 100083, China State Key Laboratory of biomembrane and Membrane Biotechnology College of Life Sciences Peking University Beijing 100871

AIM: To study the blockade of paeoniflorin (Pae) on INain the acutely isolated hippocampus neurons of mice. METHODS: The whole-cell patch clamp technique was used. RESULTS: Pae inhibited INain frequency-dependent and concentration-dependent manners, with an IC50of 271μmol/L. Pae 0.3 mmol/L shifted the activation potential of the maximal INafrom -40 mV to -30 mV, shifted the steady-state activation and inactivation curves toward more positive and negative potentials by 10.8 mV, and 18.2 mV, respectively, and postponed the recovery of INainactivation state from (4.2±0.7) ms to (9.8±1.2) ms. CONCLUSION: Pae inhibited INain mouse hippocampus neurons.

关键词： hippocampus patch-clamp techniques paeoniflorin sodium channels

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Cellular mechanism for spontaneous calcium oscillations in astrocytes

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Acta Pharmacologica Sinica 2006年第7期27卷 861-868页

作者： Tong-fei WANG~2 Chen ZHOU~2 Ai-hui TANG Shi-qiang WANG Zhen CHAI~3 State Key Laboratory of biomembrane and Membrane Biotechnology,College of Life Sciences,Peking University,Beijing 100871,China State Key Laboratory of biomembrane and Membrane Biotechnology College of Life Sciences Peking University Beijing China

Aim:To determine the Ca2+source and cellular mechanisms of spontaneous Ca2+oscillations in hippocampal ***:The cultured cells were loadedwith Fluo-4 AM,the indicator of intracellular Ca2+,and the dynamic Ca2+tran-sients were visualized with confocal laser-scanning ***:Thespontaneous Ca2+oscillations in astrocytes were observed first in co-culturedhippocampal neurons and *** oscillations were not affected bytetrodotoxin(TTX)treatment and kept up in purity cultured *** Ca2+oscillations were not impacted after blocking the voltage-gatedCa2+channels or ethylenediamine tetraacetic acid(EDTA)bathing,indicating thatintracellular Ca2+elevation was not the result of extracellular Ca2+***,the correlation between the spontaneous Ca2+oscillations and theCa2+store in endoplasmic reticulum(ER)were investigated with *** oscillations were:1)enhanced when cells were exposed to bothlow Na~+(70 mmol/L)and high Ca2+(5 mmol/L)solution,and eliminated completelyby 2 μmol/L thapsigargin,a blocker of sarcoplasmic reticulum Ca2+-ATPase;and2)still robust alter the application with either 50μmol/L ryanodine or 400μmol/Ltetracaine,two specific antagonists of ryanodine receptors,but depressed in adose-dependent manner by 2-APB,an InsP3receptors(InsP3R)***:InsP3R-induced ER Ca2+release is an important cellular mechanismfor the initiation of spontaneous Ca2+oscillation in hippocampal astrocytes.

关键词： hippocampal astrocytes spontaneous Ca2+ oscillations endoplasmic reticulum Ca2+ store InsP3 receptors confocal laser scanning microscope

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Regulation of embryonic stem cell self-renewal and differentiation by TGF-β family signaling

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Science China(Life Sciences) 2010年第4期53卷 497-503页

作者： FEI Teng & CHEN Ye-Guang The State Key Laboratory of biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China The State Key Laboratory of biomembrane and Membrane Biotechnology School of Life Sciences Tsinghua University

Embryonic stem (ES) cells are characterized by their ability to indefinitely self-renew and potential to differentiate into all the cell lineages of the body. ES cells are considered to have potential applications in regenerative medicine. In particular, the emergence of an ES cell analogue-induced pluripotent stem (iPS) cells via somatic cell reprogramming by co-expressing a limited number of critical stemness-related transcriptional factors has solved the problem of obtaining patient-specific pluripotent cells, encouraging researchers to develop more specific and functional cell lineages from ES or iPS cells for broad therapeutic applications. ES cell fate choice is delicately controlled by a core transcriptional network, epigenetic modification profiles and complex signaling cascades both intrinsically and extrinsically. Of these signals, transforming growth factor β (TGF-β) family members, including TGF-β, bone morphogenetic protein (BMP), Activin and Nodal, have been reported to influence cell self-renewal and a broad spectrum of lineage differentiation in ES cells, in accordance with the key roles of TGF-β family signaling in early embryo development. In this review, the roles of TGF-β family signals in coordinating ES cell fate determination are summarized.

关键词： embryonic stem cell TGF-β BMP Activin Nodal self-renewal differentiation

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nduction of M2-1ike macrophages in recipient NOD-scid mice by allogeneic donor CD4＋CD25＋ regulatory T cells

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Cellular & Molecular Immunology 2012年第6期9卷 464-472页

作者： Xuelian Hu Guangwei Liu Yuzhu Hou Jianfeng Shi Linnan Zhu Di Jin Jianxia Peng Yong Zhao State Key Laboratory of biomembrane and Membrane Biotechnology Institute of ZoologyChinese Academy of SciencesBeijingChina

CD4＋CD25＋ regulatory T cells （Tregs） play an important role in maintaining host immune tolerance via regulation of the phenotype and function of the innate and adaptive immune cells. Whether allogeneic CD4＋CD25＋ Tregs can regulate recipient mouse macrophages is unknown. The effect of allogeneic donor CD4＋CD25＋ Tregs on recipient mouse resident F4/80＋macrophages was investigated using a mouse model in which allogeneic donor CD4＋CD25＋ Tregs were adoptively transferred into the peritoneal cavity of host NOD-scid mice. The phenotype and function of the recipient macrophages were then assayed. The peritoneal F4/80＋ macrophages in the recipient mice that received the allogeneic CD4＋CD25＋ Tregs expressed significantly higher levels of CD23 and programmed cell death-ligand I（PD-L1） and lower levels of CD80, CD86, CD40 and MHC II molecules compared to the mice that received either allogeneic CD4＋CD25- T cells （Teffs） or no cells. The resident F4/80＋ macrophages of the recipient mice injected with the allogeneic donor CD4＋CD25＋ Tregs displayed significantly increased phagocytosis of chicken red blood cells （cRBCs） and arginase activity together with increased IL-IO production, whereas these macrophages also showed decreased immunogenicity and nitric oxide （NO） production. Blocking arginase partially but significantly reversed the effects of CD4＋CD25＋ Tregs with regard to the induction of the M2 macrophages in vivo. Therefore, the allogeneic donor CD4＋CD25＋ Tregs can induce the M2 macrophages in recipient mice at least in part via an arginase pathway. We have provided in vivo evidence to support the unknown pathways by which allogeneic donor CD4＋CD25＋ Tregs regulate innate immunity in recipient mice by promoting the differentiation of M2 macrophages.

关键词： alternatively activated macrophages arginase classically activated macrophages immune tolerance mouse transplanta-tion

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Thymic epithelial cell development and differentiation: cellular and molecular regulation

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Protein & Cell 2013年第5期4卷 342-355页

作者： Lina Sun Haiying Luo Hongran Li Yong Zhao State Key Laboratory of biomembrane and Membrane Biotechnology Institute of ZoologyChinese Academy of SciencesBeijing 100101China

Thymic epithelial cells (TECs) are one of the most important components in thymic microenvironment supporting thymocyte development and maturation. TECs, composed of cortical and medullary TECs, are derived from a common bipotent progenitor, mediating thymocyte positive and negative selections. Multiple levels of signals including intracellular signaling networks and cell-cell interaction are required for TEC development and differentiation. Transcription factors Foxn1 and autoimmune regulator (Aire) are powerful regulators promoting TEC development and differentiation. Crosstalks with thymocytes and other stromal cells for extrinsic signals like RANKL, CD40L, lymphotoxin, fibroblast growth factor (FGF) and Wnt are also definitely required to establish a functional thymic microenvironment. In this review, we will summarize our current understanding about TEC development and differentiation, and its underlying multiple signal pathways.

关键词： thymus thymic epithelial cells Aire Foxn1 TNFR NF-κB FGFs

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Effects of Muscle Electrical Activity on the Transmission of Developing Neuromuscular Junction

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Science China Chemistry 1994年第5期37卷 573-580页

作者：汤云贵谢佐平毛健何展全赵南明 State Key Laboratory of biomembrane and Membrane Biotechnique Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 PRC

Miniature endplate potentials (MEPPS) caused by the spontaneous release of ACh from the growth cone of cholinergic neurons, are recorded by the whole-cell patch-clamp technique on a large number of 1-day cultured myoballs which have contact neurites of co-cultured neurons. Both muscle cell and neuron are dissociated from the 1-day-old (about stage 20) Xenopus embryo. Frequency and/or amplitude of MEPPs can obviously increase after the repetitive high-level depolarization caused by the stimuli on muscle cells. No detectable changes of single ACh receptor channel property are observed by using the single-channel recording technique. These results suggest that the mechanism of the increase of MEPPs after electrical activity of postsynaptic muscle cells probably involve some alteration of presynaptic membrane.

关键词： electrical activity of muscle cell patch-clamp technique miniature endplate potentials (MEPPs) acetylcholine (ACh) receptor channel.

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Genistein inhibits human TNF-α-induced porcine endothelial cell adhesiveness for human monocytes and natural killer cells

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Chinese Science Bulletin 2002年第6期47卷 470-475页

作者： Xiaofeng Zhang Yan Gu Zhimin Feng Liqin Ban Meifu Feng National Laboratory of biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Beijing China

Cellular immune response is a major barrier to xenotransplantation. Human tumor necrosis factor-α (hTNF-α) possesses cross-species activity and directly amplifies the immune rejection via the upregulation of adhesion molecules on porcine endothelium. We investigated the role of protein tyrosine phosphorylation in the induction of expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1), and the augmentation of adhesion of human peripheral blood monocytes (PBMo) and natural killer cells (PBNK), after rhTNF-α-stimulation of porcine aortic endo-thelial cells (PAEC) in vitro. rhTNF-α-increased adhesiveness of PAEC for both PBMo and PBNK was dose-dependently reduced by pretreatment of PAEC with the selective protein tyrosine kinase (PTK) inhibitor genistein. The inhibitory effect occurred at the early time of PAEC activation triggered by rhTNF-α, and was completely reversible. PTK activity assay indicated that genistein also suppressed rhTNF-α stimulated activation of protein tyrosine

关键词： genistein human tumor necrosis factor-α (hTNF-α) porcine aortic endothclial cells (PAEC) human peripheral blood monocytes (PBMo) human peripheral blood natural killer cells (PBNK) cell adhesion.

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Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso(Welw) root bark

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Journal of Integrative Medicine 2019年第6期17卷 446-454页

作者： Olubukola Titilope Oyebode Foluso Olayemi Ogunbiyi Olufunso Olabode Olorunsogo Laboratories for biomembrane Research and Biotechnology Department of Biochemistry Faculty of Basic Medical Sciences College of Medicine University of Ibadan

Objective: Several pathologies arise from the inappropriate opening of the mitochondrial permeability transition(mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin(STZ)-induced diabetic rat ***: Different solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso(MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control(distilled water);B, STZ(65 mg/kg;diabetic control);C, STZ + MFFM(25 mg/kg);D, STZ + MFFM(50 mg/kg);E, STZ + glibenclamide(5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using ***: In vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calciumdependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant(P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde(MDA) levels in STZ-induced diabetes were significantly(P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiab

关键词： Mitochondria Ficus mucoso Permeability transition Cytochrome c

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