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SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

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Science China(Life sciences) 2013年第1期56卷 19-25页

作者： JIA YuYan GAO Peng CHEN HouZao WAN YanZhen ZHANG Ran ZHANG ZhuQin YANG RuiFeng WANG Xu XU Jing LIU DePei State Key laboratory of medical Molecular Biology Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences & Peking Union Medical College

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.

关键词： ICAM-1 血管内皮细胞诱导条件离子霉素 PMA 人脐静脉内皮细胞细胞间粘附分子-1 动脉粥样硬化

Formulation of self-nanoemulsifying drug delivery systems containing monoacyl phosphatidylcholine and Kolliphor^(■) RH40 using experimental design

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Asian Journal of Pharmaceutical sciences 2018年第6期13卷 536-545页

作者： Thuy Tran Thomas Rades Anette Müllertz department of Pharmacy Faculty of Health and Medical Sciences University of Copenhagen Bioneer: FARMA Faculty of Health and Medical Sciences University of Copenhagen

The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be inadequate to analyse the effect of each excipient and their potential interactions on the emulsion droplet size formed when dispersing the SNEDDS in an aqueous environment. The current study investigates the emulsion droplet sizes formed from SNEDDS containing different levels of the natural surfactant monoacyl phosphatidylcholine to reduce the concentration of the synthetic surfactant polyoxyl 40 hydrogenated castor oil(Kolliphor ~? RH40). Monoacyl phosphatidylcholine was used in the form of Lipoid S LPC 80(LPC, containing approximately 80% monoacyl phosphatidylcholine, 13% phosphatidylcholine and 4% concomitant components). The investigated SNEDDS comprised of long-chain or medium-chain glycerides(40% to 75%), Kolliphor ~? RH40(5% to 55%), LPC(0 to 40%) and ethanol(0 to 10%). D-optimal design, multiple linear regression, and partial least square regression were used to screen different SNEDDS within the investigated excipient ranges and to analyse the effect of each excipient on the resulting droplet size of the dispersed SNEDDS measured by dynamic light scattering. All investigated formulations formed nano-emulsions with droplet sizes from about 20 to 200 nm. The use of mediumchain glycerides was more likely to result in smaller and more monodisperse droplet sizes compared to the use of long-chain glycerides. Kolliphor~? RH40 exhibited the most significant effect on reducing the emulsion droplet sizes. Increasing LPC concentration increased the emulsion droplet sizes, possibly because of the reduction of Kolliphor~? RH40 concentration. A higher concentration of ethanol resulted in an insignificant reduction of the emulsion droplet size. The study provides different ternary diagrams of SNEDDS containing LPC and Kolliphor ~? RH40 as a reference for form

关键词： Monoacyl phosphatidylcholine Self-nanoemulsifying drug delivery systems D-optimal design Polyoxyl 40 hydrogenated castor oil Kolliphor^(■)(RH40) Droplet size Cryogenic transmission electron microscopy

Computed tomography angiographic study of surgical anatomy of thyroid arteries:Clinical implications in neck dissection

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World Journal of Radiology 2023年第6期15卷 182-190页

作者： Yashu Bhardwaj Brijendra Singh Pooja Bhadoria Rashmi Malhotra Swarnava Tarafdar Kanchan Bisht department of Anatomy All India Institute of Medical SciencesRishikesh 249203UttarakhandIndia department of Radiodiagnosis All India Institute of Medical SciencesRishikesh 249203UttarakhandIndia

BACKGROUND The course and variations of thyroid arteries must be understood by surgeons to prevent bleeding during operative procedures of the thyroid *** is limited scientific literature regarding the radiological anatomy of thyroid arteries in this geographical area,the Garhwal region of Sub-Himalayan belt,which is considered to be the endemic belt of *** tomography angiography provides a three-dimensional orientation of the vascular and surgical anatomy of the entire cervical *** To estimate the proportion of variation in origin of thyroid arteries using Computed Tomography *** Using Computed Tomography Angiography,the presence and origin of the superior thyroid artery,inferior thyroid artery,and thyroid ima artery were observed and *** Out of total 210 subjects,superior thyroid artery was seen to be emerging from external carotid artery in 77.1%*** artery was found to be originating at the level of bifurcation of common carotid artery in 14.3%cases,whereas in 8.6%cases,it emerged as a direct branch of the common carotid ***,the inferior thyroid artery was observed to be emerging from thyrocervical trunk,subclavian artery and vertebral artery in 95.7%cases,3.3%and 1%cases,*** ima artery was also reported in a subject,arising from the brachiocephalic *** To avoid vascular injuries,excessive and uncontrollable bleeding,intra-operative difficulties,and post-operative issues,it is imperative for surgeons to be aware of the course and variations of thyroid arteries。

关键词： Thyroid arteries Computed tomography angiography Origin Variation

KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4217-4233页

作者： Cancan Zheng Xiaomei Yu Taoyang Xu Zhichao Liu Zhili Jiang Jiaojiao Xu Jing Yang Guogeng Zhang Yan He Han Yang Xingyuan Shi Zhigang Li Jinbao Liu Wen Wen Xu Key laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education Institutesthe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University.Shanghai 200030China department of Radiation Oncology the Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Thoracic Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060China Guangdong Provincial Key laboratory of Protein Modification and Degradation State Key Laboratory of Respiratory Diseaseand School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhou 511495China

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer,but its function and regulatory network in metastasis remain unclear.A comprehensive investigation of key regulators in cancer metastasis is urgently *** sequencing(RNA-seq)of primary esophageal squamous cell carcinoma(ESCC)and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4(KCTD4)as a driver of cancer ***4 expression was found upregulated in metastatic *** KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in ***,KCTD4 binds to CLIC1 and disrupts its dimerization,thus increasing intracellular Ca^(2+)level to enhance NFATc1-dependent fibronectin ***4-induced fibronectin secretion activates fibroblasts in a paracrine manner,which in turn promotes cancer cell invasion via MMP24 signaling as positive ***,a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4-CLIC1 interaction,providing a potential therapeutic *** together,our study not only uncovers KCTD4 as a regulator of calcium homeostasis,but also reveals KCTD4/CLIC1-Ca^(2+)-NFATc1-fibronectin signaling as a novel mechanism of cancer *** findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

关键词： Cancermetastasis Calcium homeostasis NFAT signaling Fibroblasts Esophageal cancer

Modeling CO_(2)Emission in Residential Sector of Three Countries in Southeast of Asia by Applying Intelligent Techniques

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Computers, Materials & Continua 2023年第3期74卷 5679-5690页

作者： Mohsen Sharifpur Mohamed Salem Yonis M Buswig Habib Forootan Fard Jaroon Rungamornrat Clean Energy Research Group Department of Mechanical and Aeronautical EngineeringEngineering IIIUniversity of PretoriaPretoriaSouth Africa department of medical Research China Medical University HospitalChina Medical UniversityTaichungTaiwanChina School of Electrical and Electronic Engineering Universiti Sains Malaysia(USM)Nibong Tebal14300PenangMalaysia Institute of Sustainable and Renewable Energy ISuRE Faculty of EngineeringUniversityMalaysia Sarawak department of Renewable Energies Faculty of New Sciences and TechnologiesUniversity of TehranTehranIran Center of Excellence in Applied Mechanics and Structures Department of Civil EngineeringFaculty of EngineeringChulalongkorn UniversityBangkok10330Thailand

Residential sector is one of the energy-consuming districts of countries that causes CO_(2)emission in large *** this regard,this sector must be considered in energy policy making related to the reduction of emission of CO_(2)and other greenhouse *** the present work,CO_(2)emission related to the residential sector of three countries,including Indonesia,Thailand,and Vietnam in Southeast Asia,are discussed and modeled by employing Group Method of Data Handling(GMDH)and Multilayer Perceptron(MLP)neural networks as powerful intelligent *** to modeling,data related to the energy consumption of these countries are represented,discussed,and ***,to propose a model,electricity,natural gas,coal,and oil products consumptions are applied as inputs,and CO_(2)emission is considered as the model’s *** obtained R^(2) values for the generated models based on MLP and GMDH are 0.9987 and 0.9985,***,values of the Average Absolute Relative Deviation(AARD)of the regressions using the mentioned techniques are around 4.56%and 5.53%,*** values reveal significant exactness of the models proposed in this article;however,making use of MLP with the optimal architecture would lead to higher accuracy.

关键词： CO_(2)emission GMDH MLP intelligent techniques energy consumption

Epigenetic checkpoint blockade:new booster for immunotherapy

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2272-2274页

作者： Ziqiao Wang Bingjing Wang Xuetao Cao department of Immunology Institute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina laboratory of Immunity and Inflammation College of Life SciencesNankai UniversityTianjinChina

In a recent study published in Nature,Griffin et *** that blockade of SETDB1 enhances anti-tumor immune response,shedding new light on the potential epigenetic therapy to specifically improve immune checkpoint blockad... 详细信息

关键词： al. immunotherapy immune

Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells

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Genomics, Proteomics & Bioinformatics 2022年第1期20卷 70-86页

作者： Chen Zhang Xueshuai Han Jingkun Liu Lei Chen Ying Lei Kunying Chen Jia Si Tian-yi Wang Hui Zhou Xiaoyun Zhao Xiaohui Zhang Yihua An Yueying Li Qian-Fei Wang CAS Key laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and DevelopmentBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China University of Chinese Academy of sciences Beijing 100049China department of medical Experimental Center Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266035China Qingdao Key lab of Mitochondrial Medicine Qingdao 266035China International department Liangxiang CampusBeijing University of Chinese MedicineBeijing 102401China Yihua Biotechnology Co. Ltd.Beijing 100041China Peking University People’s Hospital Peking University Institute of HematologyBeijing 100044China department of Functional Neurosurgery Third Medical CenterGeneral Hospital of Chinese PLABeijing 100039China

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodulatory ***,the exact characteristics of MSCs remain largely *** singlecell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton’s jelly,we revealed five distinct *** developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent *** stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness ***,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3^(+T) cell proliferation in vitro,supporting the role of this population in *** summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and *** findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.

关键词： Mesenchymal stem cell Single-cell RNA sequencing Heterogeneity Lineage trajectory Immune regulation

Iron chelator daphnetin against Pneumocystis carinii in vitro

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Chinese medical Journal 2004年第11期117卷 1704-1708页

作者：叶彬郑玉强武卫华张静 department of Parasitology Chongqing University of Medical SciencesChongqing 400016China department of laboratory Medicine Children’s HospitalChongqing University of Medical SciencesChongqing 400014China

Background Although there are several drugs and drug combinations for the treatment of Pneumocystis carinii (P. carinii) pne umonia, all drugs have the toxicity as well as low efficacy. Iron chelators have been proposed as a source of new drugs for combating these infections. We hypothesized that iron chelators would suppress the growth of P. carinii by deprivation of the nutritional iron required for growth. In this study, a short-term axenic culture system of P. carinii was established. Daphnetin (7,8-dihydroxycoumarin), a known iron chelator, was demonstrated to exhibit in vitro activity against P. carinii in this system. Methods P. carinii organisms were obtained from the lungs of immunosuppressed rats. The culture system consisted of Iscove Dulbecco Eagle’s Minimum Essential Medium (IMDM), supplemented with S-adenosyl-L-methionine, N-acetylglucosamine, putrescine, L-cysteine, L-glutamine, 2-mercaptoethanol, and fetal bovine serum, and was maintained at 37℃, in 5% CO 2, 95% O 2, at the optimal pH of 8.0. The culture system was used to assess the effect of daphnetin on the proliferation of P. carinii organisms. The ultrastructures of the treated organisms were observed by transmission electron *** The number of cysts and trophozoites increased 8- to 9-fold and 11- to 12-fold, respectively, after 10 days of culture. Daphnetin was found to suppress the growth of P. carinii in a dose-dependent manner at concentrations between 1 μmol/L and 20 μmol/L. The inhibitory activity was suppressed by the chelation of daphnetin with ferrous sulfate in a 2∶1 molar ratio, but it was not suppressed by mixing the culture medium with magnesium sulfate. Reduction of P. carinii numbers after treatment with daphnetin correlated with morphological changes in the organisms, as determined by transmission electron *** Daphnetin can suppress the growth of P. carinii in vitro. The efficacy o f daphnetin in suppressing the the growth of P. carinii i

关键词： Pneumocystis carinii daphnetin ultrastructures

Association between Vitamin D Insufficiency and the Risk for Gestational Diabetes Mellitus in Pregnant Chinese Women

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Biomedical and Environmental sciences 2012年第4期25卷 399-406页

作者： WANG Ou NIE Min HU Ying Ying ZHANG Kui LI Wei PING Fan LIU Jun Tao CHEN Li Meng XING Xiao Ping department of Endocrinology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Key laboratory of Endocrinology Ministry of Health Beijing 100730 China department of Obstetrics& Gynecology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 China department of Nephrology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 China

Objective To investigate the association between vitamin D deficiency and risk of gestational diabetes rnellitus （GDM） in pregnant Chinese women. Methods A nested case-control study was conducted. Clinical and biochemical data were analyzed for 200 subjects with GDM and 200 subjects with normal glucose tolerance （NGT）. Results The median （interquartile range） serum 25-hydroxyvitamin D （25OHD） levels were 22.39 （17.67, 29.38） and 25.86 （19.09, 34.88） nmol/L in the GDM and NGT groups, respectively. Rates of 25OHD deficiency or insufficiency were significantly higher in the GDM group than in the NGT group. Subjects with 25OHD levels 〈25 nmol/L had a 1.g-fold higher risk of GDM compared with subjects with higher vitamin D levels. In the GDM group, serum 25OHD was independently associated with HbAlc and insulin resistance after adjusting for confounding factors. In the NGT group, serum 25OHD was independently associated with fasting plasma glucose and systolic blood pressure after adjusting for maternal age and other confounding factors. Conclusion 2SOHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM.

关键词： Gestational diabetes mellitus Vitamin D insufficiency Chinese women