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Expression of human hepatic lipase negatively impacts apolipoprotein A-Ⅰ production in primary hepatocytes from Lipc-null mice

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The Journal of Biomedical Research 2014年第3期28卷 201-212页

作者： Michelle Bamji-Mirza wandong zhang Zemin Yao Department of Biochemistry Microbiology & ImmunologyUniversity of Ottawa Department of Pathology and Laboratory Medicine University of Ottawa Human Health Therapeutics Portfolio Life Sciences DivisionNational Research Council Canada Ottawa Institute of Systems Biology University of Ottawa

This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） *** levels of secreted and cell-associated apoA-I were contrasted between primary hepatocytes isolated from Lipc-nuW and C57BL/6 mice,and between Lipc-nuW hepatocytes transfected with either hHL-encoding or control *** HSPG-binding deficient hHL protein（hHLmt） was used to determine the impact of cell surface binding on HL *** of apoA-I in conditioned media of primary hepatocytes isolated from Lipc-nuW mice was increased as compared to that from C57BL/6 *** labeling experiments showed that secretion of ＇＇S-apoA-I from Lipc-nuW cells was significantly higher than that from C57BL/6 *** of hHL in Lipc-nuW hepatocytes,through adenovirus-mediated gene transfer,resulted in decreased synthesis and secretion of ＇S-apoA-I,but not S-apoE,as compared with cells transfected with control *** of HSPG-binding deficient hHLmt in Lipc-nuW cells also exerted an inhibitory effect on apoA-I production,even though hHLmt displayed impaired exit from the endoplasmic reticulum as compared with *** fractionation revealed that expression of hHL or hHLmt led to increased microsome-association of apoA-I relative to non-transfected *** of hHL negatively impacts hepatic production of apoA-I.

关键词： high density lipoprotein heparan sulphate proteoglycans ABCA1 endoplasmic reticulum adenovirus

Oligodendrocyte transcription factor 1 mRNA and protein expression in organotypic rat brain slices

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Neural Regeneration Research 2010年第21期5卷 1639-1643页

作者： Hong Cui Lijun Yang Dezhuang Huang wandong zhang Weijuan Han Yanqing Yao Wenxing Jiang Pediatrics Department Beijing Friendship Hospital Capital Medical University Beijing 100050 China Hepatitis Institute Beijing YouAn Hospital Capital Medical University Beijing 100054 China Institute for Biological Sciences National Research Council of Canada Ottawa K1A OR6 Ontario Canada

Numerous studies have confirmed that oligodendrocyte transcription factor 1 （Olig-1） is vital for myelin repair. However, the effects of hypoxia and ischemia on Olig-1 expression remain unknown. In this study, Olig-1 mRNA and protein expressions were analyzed by in situ hybridization and immunohistochemistry, to determine the expression profile of Olig-1 in rat brain slices exposed to hypoxia and ischemia. Brains were obtained from 2-day-old Sprague-Dawley rats, and sections were randomly assigned to control and hypoxia/ischemia groups. Hematoxylin-eosin staining revealed karyorrhexis and karyopyknosis in cells from the hypoxia/ischemia group. Under electron microscopy, mitochondria swelling and neuropil edema were observed in the hypoxiaJischemia group. Olig-1 mRNA and protein expressions were increased at 1 day after hypoxia and ischemia treatment. These results suggest that in situ hybridization and immunohistochemistry could be used simultaneously to detect mRNA and protein expression in brain slices.

关键词： oligodendrocyte transcription factor 1 double staining brain slices immunohistochemistry in situ hybridization hypoxia and ischemia

海上超高温高压井取心工具关键性能评价及应用研究

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中国科技论文 2024年第7期19卷 760-768页

作者：张波涛罗鸣张万栋刘峰孙艳军中海石油(中国)有限公司海南分公司工程技术作业中心海口570100 中海石油(中国)有限公司湛江分公司工程技术作业中心广东湛江524057 中石化胜利石油工程有限公司钻井工艺研究院山东东营257017

海上油田部分深井和超深井储层存在超高温、超高压、安全压力窗口窄以及地质条件复杂的情况,钻井取心作业过程中易发生井漏以及卡钻等复杂情况,使用常规的钻井取心工具取心效率低,无法满足取心作业要求。因此,在分析了海上超高温高压井... 详细信息

海上油田部分深井和超深井储层存在超高温、超高压、安全压力窗口窄以及地质条件复杂的情况,钻井取心作业过程中易发生井漏以及卡钻等复杂情况,使用常规的钻井取心工具取心效率低,无法满足取心作业要求。因此,在分析了海上超高温高压井取心技术难点的基础上,设计了一套适合海上超高温高压井的免投球钻井取心工具,并对螺纹连接强度、分水接头和取心钻头水动力学以及悬挂总成摩阻3个关键性能参数进行了评价。结果表明:取心工具在室温和超高温(250℃)条件下的螺纹强度均能满足行业标准要求,分水接头及取心钻头结构设计合理,产生的压降较小,悬挂总成的摩擦阻力较小,内筒工作比较稳定。海上超高温高压井钻井取心工具在乐东区块2口超高温高压井取心作业过程中进行了成功应用,WC-9井和LS-2井的井底温度分别为205.2℃和212.3℃,压力系数分别为2.29和2.31,2口井的取心收获率均达到了100%,岩心成柱性能好,取心钻头未明显磨损,应用效果较好,适合在海上类似超高温高压井进行推广应用。

关键词：超高温高压井取心工具关键参数螺纹连接强度水动力学摩阻

Mechanism studies of Xinfeng capsule on improving cardiovascular function though toll-like receptor 4/nuclear factor kappa B pathway in a rat model of adjuvant arthritis

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Journal of Traditional Chinese Medicine 2017年第1期37卷 116-123页

作者： Wang Yuan Liu Jian Huang Chuanbing Sun Yue zhang wandong Wan Lei Zong Ruikai Wang Yali Department of Rheumatology First Affiliated HospitalAnhui University of Traditional Chinese MedicineHefei 230038China Graduate Faculty Anhui University of Traditional Chinese MedicineHefei 230038China

OBJECTIVE: To observe the impact of Xinfeng capsule(XFC) on cardiovascular function in adjuvant arthritis(AA) model rats and investigate the mechanism though toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) signaling ***: Seventy rats were randomly divided into seven groups: normal control(NC), model control(MC), tripterygium glycosides tablet(TPT),methotrexate(MTX), high, moderate and low dose XFC group. The administration began from day 19 after modeling for 30 day. Paw swelling, arthritic in-dex(AI), cardiac function indexes and myocardial pathological pattern were detected. The expression of TLR4, myeloid differentiation factor(My D) 88, interleukin-1 receptor-associated kinase(IRAK) 1, tumor necrosis factor receptor associated factor(TRAF) 6, NF-κB, tumor necrosis factor-alpha(TNF-α) proteins in myocardial tissue were determined by western blot ***: Paw swelling and AI in MC group increased in MC group(P 0.05). Left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),heart rate(HR) were elevated in MC group(P <0.01), and ± dp/dtmax and CI were reduced(P <0.01); while LVSP, LVEDP and HR declined and ±dp/dtmax, CI improved in high dose XFC group(P <0.05 or P < 0.01). LVSP in high dose XFC group were reduced more than other treatment groups(P <0.05 or P < 0.01). The improvements on LVEDP, dp/dt-max were superior to MTX and low dose XFC group, and the improvement on CI was better than low dose XFC group(P < 0.05 or P < 0.01). Myocardial fibers arranged irregular in MC group with intracellular edema and mitochondria damage. The modifications on myocardial structural were shown in each treatment group, but more prominent in TPT, high and moderate dose XFC group. The proteins of TLR4, My D88, IRAK1, TRAF6, NF-κB, TNF-αwere highly expressed in MC group, and those proteins declined in high and moderate dose XFC group(P < 0.05 or P < 0

关键词： Arthritis experimental Cardiovascular diseases Toll-like receptor 4 NF-kappa B Signal transduction Xinfeng capsule

Efficacy and safety of Xinfeng capsule in the treatment of osteoarthritis:a multicenter, randomized, double-blinded, controlled trial

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Journal of Traditional Chinese Medicine 2020年第2期40卷 284-295页

作者： Liu Jian Wang Yuan Sun Yue Huang Chuanbing Chen Xi zhang wandong He Liyun James Cheng-Chung Wei Department of Rheumatism Immunity The First Affiliated HospitalAnhui University of Chinese MedicineHefei 230031China the Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China Division of Allergy Immunology and RheumatologyChung Shan Medical University HospitalInstitute of MedicineChung Shan Medical UniversityGraduate Institute of Integrated MedicineChina Medical UniversityTaichungTaiwan China

OBJECTIVE: To evaluate the efficacy and safety of Xinfeng capsule(XFC) in patients with osteoarthritis(OA).METHODS: This was a multicenter, double-blinded,randomized, controlled, clinical trial. Patients with OA were assigned to the XFC group [treated with XFC and a glucosamine(GS) placebo, n = 129] or the GS group(treated with GS and an XFC placebo,n = 126). Both groups were treated for 4 weeks. The primary endpoint was the difference between the two groups in the Western Ontario and Mc Master Universities OA(WOMAC) index total score at 4 th week. The secondary endpoints were the visual analogue scale for pain, Lequesne index, function influence index rating, quality of life as assessed by the Short Form-36, erythrocyte sedimentation rate,and C-reactive protein concentration at baseline and at second week and 4 th week. Bone mineral density were checked by X ray absorptiometry at baseline and 4 th ***: After 4 weeks of treatment, all patients in both groups showed similar significant improvements compared with baseline. There were no significant differences between groups regarding pain relief, bilateral femoral bone mineral density, and laboratory indices such as erythrocyte sedimentation rate and C-reactive protein *** groups had a significantly lower function influence index rating score and curative effect for each sign/symptom in week 4 than in week 0, and these changes did not significantly differ between groups. XFC was superior to GS in improving the WOMAC index total score, WOMAC scores for function and stiffness, integrated symptoms, physiological function, energy, emotional function, mental health, and health changes. Fourteen adverse reactions were reported, and the incidence of adverse reactions did not significantly differ between groups. The most common adverse reactions were hepatic impairment, kidney functional damage,gastrectasia, and facial skin allergy. The types of adverse reactions did not differ between ***

关键词： Osteoarthritis Glucosamine Quality of life Treatment outcome Randomized controlled trial Xinfeng capsule

Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs

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Neuroscience Bulletin 2019年第6期35卷 996-1010页

作者： Yuan Li Xueying Sun Houfu Liu Liang Huang Guofeng Meng Yu Ding Wenji Su Jiaqi Lu Sophie Gong Georg C.Terstappen Ru zhang wandong zhang Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-Based Bio-medicineCollaborative Innovation Center for Brain ScienceSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Platform Technology&Sciences GlaxoSmithKline China R&D CentreShanghai 201203China Neurosciences Therapeutic Area Unit GlaxoSmithKline China R&D CentreShanghai 201203China Human Health Therapeutics Research Centre National Research Council of Canada Faculty of Medicine University of OttawaOttawa K1A0R6Canada

An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous *** many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug ***-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB ***, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 ***2±230 ***2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 ***2 to 4185 ***2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

关键词： Blood-brain barrier Drug transport Induced pluripotent stem cell Cell differentiation Prediction of in vivo permeability

Nano-formulated delivery of active ingredients from traditional Chinese herbal medicines for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1525-1541页

作者： Qi Shang wandong Liu Faith Leslie Jiapei Yang Mingmei Guo Mingjiao Sun Guangji zhang Qiang zhang Feihu Wang School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Blood-stasis-toxin Syndrome of Zhejiang Province Hangzhou 310053China Department of Chemical and Biomolecular Engineering Whiting School of Engineeringthe Johns Hopkins UniversityBaltimoreMD 21218USA Traditional Chinese Medicine“Preventing Disease”Wisdom Health Project Research Center of Zhejiang Hangzhou 310053China Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

关键词： Chinese herbal medicines Nano-formulation Activeingredients Drug delivery Cancer immunotherapy Innate immune system Adaptive immune system

Trade-offs between chemical resistance to herbivory and responses to abiotic stresses in invasive plants

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Journal of Plant Ecology 2024年第2期17卷 18-23页

作者： Lifeng Zhou wandong Yin Jianqing Ding State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China

INTRODUCTION Plants change their traits to respond to shifting environments,enabling them to defend against biotic stresses such as herbivorous insects,and/or tolerate abiotic stresses,such as extreme climate(Callaway et al.2022;zhang et al.2018,2022).There are often costs when plants produce secondary chemicals to adapt to varying biotic or abiotic environments(Abdala-Roberts et al.2016).

关键词： traits ). environments

Prognostic significance of MDR-1 P-glycoprotein expression in breast cancer

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Journal of Nanjing Medical University 2008年第3期22卷 148-152页

作者： Huilin zhang wandong zhang Fengshan Li Department of Obstetrics and Gynecology Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University Nanjing 210004 Jiangsu Province China Institute for Biological Sciences National Research Council of Canada Ottawa Ontario Canada K1A OR6

Objective： To investigate the expression of MDR-1 P-glycoprotein（MDR-1 Pgp） in breast cancer and analyze its correlation to the biological behavior and prognosis of the disease. Methods：The expression of MDR-1 Pgp was examined in 75 cases of breast cancer patients by using three different monoclonal antibodies（JSB1, C219 and C494） with S-P immunohistochemisty. These patients were followed up for 5 years, and the correlation between MDR-1 Pgp expression, survival rate and lymph metastasis was analyzed. Results： Positive detection of MDR-1 Pgp by JSB1, C219 and C494 in 75 cases of breast cancer was 86.7%, 48% and 85.3%, respectively. MDR-1 Pgp expression was not related to ages of patients （P 〉 0.05）. JSBl-detected expression of MDR-1 Pgp was related to lymph node metastasis（P〈 0.05）; while C219 and C494 were not（P 〉 0.05）. The patients with MDR-1 Pgp expression positively detected by either two of the three antibodies, had five-year survival rate that was significantly higher than those positively detected by all the three antibodies（P 〈 0.05）. Conclusion：Three antibodies should be used simultaneously to detect MDR-1 Pgp expression in breast cancer. Positive MDR-1 Pgp expression in breast cancer detected by all the three antibodies may represent a poor prognosis; while positive MDR-1 Pgp detection by JSB1 and C494 is associated with lymph metastasis.

关键词： Breast cancer MDR-1 P-glycoprotein Immunohistochemistry Prognosis Metastasis