复方黄连降糖片对GK大鼠糖脂代谢紊乱的影响

目的:观察复方黄连降糖片对2型糖尿病(T2DM)糖脂代谢紊乱的影响。方法:将27只GK大鼠按血糖随机分为模型组,复方黄连降糖片组(中药组)与二甲双胍组(西药组),饲以高脂饮食;另设Wistar大鼠12只作为正常组。各组给予饮用水或药物灌胃8周,并在治疗后测定空腹血糖(FPG)、糖负荷2h血糖(2hPG)、随机血糖(RPG)、糖化血红蛋白(HbAlc)、血清胰岛素(Ins)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肝脏甘油三酯(Liver-TG)。结果:与正常组比较,模型组大鼠出现糖脂代谢紊乱,血糖、HbAlc、LDL-C、Liver-TG、TC显著升高,Ins显著降低。与模型组比较,治疗组血糖、HbAlc、TC、LDL-C、Liver-TG均显著降低,Ins有升高趋势。结论:复方黄连降糖片能显著降低GK大鼠的血糖、HbAlc、TC、LDL-C、Liver-TG水平,从而调整其糖脂代谢紊乱状况。     

Litomosoides carinii: macrofilariae-derived glycolipids—chromatography, serology and potential in the evaluation of anthelminthic efficacy

A preliminary characterization of the glycolipids of Litomosoides carinii macrofilariae, resolved according to their chromatographic, chemical and serological properties, has been performed. Emphasis has been placed on the neutral fraction glycolipids. These are separable on thinlayer chromatography into two groups of fast and slow migrating band components, that differ in their migration, differential chemical staining and serological traits, respectively. Serological analyses have been accomplished by thin-layer chromatography immunostaining and ELISA. Only components of the slow migrating band group react with infection serum from Litomosoides carinii-infected Mastomys coucha. Cross-reactivity experiments with homologous and heterologous infection sera of various helminthiases indicate that, epitopes bound to the neutral glycolipid fraction show structural similarity within the Nematoda, but not to the Cestoda or Trematoda. The dynamic development of specific Ig-, IgG- and IgM-anti-neutral glycolipid fraction antibody levels were correlated with the different progression of L. carinii and Brugia malayi infections in the multimammate rat, Mastomys coucha. The reduction in the dynamics of IgG- and IgM-antibody levels on chemotherapeutic treatment with the filaricides flubendazole and CGP 20376 has been related to their macrofilaricide-activity.     

Patterns of reactivity with anti-glycolipid antibodies in human primary brain tumors

Antibodies against carbohydrates of three glycolipids were used to determine patterns of immunohistochemical reactivity of histologically identifiable cell subpopulations in 101 human primary brain tumors. For all tumor types fibrillary cells, polar cells, and gemistocytes (commonly seen in astrocytomas and ependymomas) stained more frequently for galactosylcerebroside with mAbO1 than small tumor cells and macrophages. Frequency of staining for sulfatide with mAbO4 was fibrillary > polar > small cells = macrophages. Gemistocytes stained more frequently with mAbO4 than polar cells in all tumors except low grade astrocytomas. These data indicate that tumors classified on histological grounds as astrocytic are often stained with antibodies that recognize oligodendrocytes and their progenitors. Thus, anti-glycolipid antibodies used in the study of developmental lineage may offer useful tools for classification of human brain tumors. Staining of fibrillary cells, polar cells, and gemistocytes for paragloboside directly with mAb F1H11 was much less common than with mAbO1, but this increased by pretreatment of the tissues with neuraminidase (F1H11 + N). Of particular note was the finding that small tumor cells frequently stained with F1H11 + N. Evidence that these were not macrophages was obtained using double immunostaining with F1H11 + N and anti-macrophage antibodies. In astrocytomas the frequency of small tumor cells immunostained with F1H11 + N was high grade > anaplastic > low grade, demonstrating a correlation of this tumor cell population with more F1H11 + N may be of value in identifying small, ana-plastic tumor cells, especially in small biopsies or tissue taken adjacent to the main tumor mass. Copyright © 1994 Wiley-Liss, Inc.     

Are N‐glycolylneuraminic acid (Hanganutziu–Deicher) antigens important in pig‐to‐human xenotransplantation?

BACKGROUND: N-glycolylneuraminic acid (NeuGc) epitopes, so called Hanganutziu-Deicher (HD) antigens, which are widely expressed on endothelial cells of all mammals except humans, are considered to be potential targets for natural and elicited anti-nonGalalpha1-3 Gal (Gal) antibodies in humans. We previously reported that anti-NeuGc antibodies were not detected in healthy humans by enzyme-linked immunosorbent assay (ELISA) using NeuGc-GM3-coated plates, and no antibody production was observed in patients with a history of exposure to pig cells. However, a recent paper has revealed that (i) anti-NeuGc antibodies to porcine red blood cells (PRBC) are detectable in most healthy humans, and (ii) the majority of anti-nonGal antibodies are specific for NeuGc epitopes. The purpose of this study was to reassess whether NeuGc is important as an immunogenic nonGal epitope. METHODS: The binding of antibodies to PRBC and porcine aortic endothelial cells (PAEC) was compared. Cells were treated with (i) alpha-galactosidase, and then (ii) neuraminidase, which digests sialic acids, including NeuGc epitopes. Cells were incubated with human pooled sera, and applied to flow cytometric analysis. After enzyme digestion, almost complete reduction of Gal and NeuGc expression was confirmed by GS-IB4 and HU/Ch2-7 (a chicken monoclonal antibody against HD antigens), respectively. Trypsin, which removes membrane glycoproteins, and endoglycoceramidase which cleaves glycolipids, were used for differentiating between NeuGc-containing glycoproteins and glycolipids. RESULTS: Neuraminidase-treatment reduced the binding of immunoglobulin G (IgG) antibodies to PRBC; about half of the anti-nonGal IgG antibodies to PRBC were directed to NeuGc. In contrast, anti-nonGal antibodies to PAEC were not directed to NeuGc. Trypsin-treatment markedly reduced the expression of NeuGc only on PRBC. Endoglycoceramidase-treatment was followed by a greater reduction in NeuGc epitopes on PAEC than on PRBC. Most NeuGc on PRBC appeared to be linked to proteins, but most NeuGc on PAEC was expressed on glycolipids. CONCLUSIONS: Carbohydrate structures on PRBC are different from those on PAEC. Healthy human sera contain anti-nonGal IgG antibodies to NeuGc expressed on PRBC, but not on PAEC. We speculate that anti-nonGal IgG antibodies to PRBC can recognize both NeuGc and protein, and this may be the reason why such antibodies have not been detected by ELISA. A definite conclusion about the immunogenicity of NeuGc has not been obtained. More sera from patients (not from non-human primates) sensitized with porcine cells or organs need to be studied.     

Glycolipid and p 40 are the binding sites in the sheep erythrocyte and T-lymphocyte membrane responsible for rosette formation

By coupling the major glycoprotein and total glycolipid of the sheep erythrocyte membrane to agarose beads it could be demonstrated that only lipid-beads formed rosettes with peripheral blood lymphocytes. Lipid-beads and sheep erythrocytes formed double rosettes with peripheral blood lymphocytes. Trypsinization of lymphocytes destroyed the rosette formation with lipid-beads. Subfractionation of the lipid by thin-layer chromatography revealed 8 different subfractions, 3 of them when coupled to agarose beads showed rosette formation. When the lipid was coupled to radioactive albumin, a protein of molecular weight 40,000 was labeled in two T-lymphocyte plasma membranes but not in B-lymphocyte plasma membranes. It is concluded that a lipid-protein interaction, involving the lipid of the erythrocyte and the p 40 of the lymphocyte membrane, is responsible for rosette formation of T-lymphocytes.     

非酒精性脂肪肝与骨质疏松间的生物信息学关系

目的 通过生物信息学相关技术方法依托相关数据库探讨非酒精性脂肪肝与骨质疏松之间的相互影响机制。方法 分别以骨质疏松及非酒精性脂肪肝为关键词在相关疾病数据库( Disgenet、TTD、OMIM、Drugbank、Genecards)中筛选相关基因,去重整合后将两组预测靶基因进行映射得到关键靶点,通过STRING网站获得靶点PPI互相作用网络,根据degree值筛选出核心靶点并通过 DAVID 数据库进行GO富集分析以及 KEGG 通路分析。结果 通过相关疾病数据库搜索筛选出与骨质疏松症和非酒精性脂肪肝相关靶点分别为 875 个和952个,映射出关键靶点217个,以degree≥36筛选出核心靶点24个并导入 DAVID 数据库获得78项GO富集结果（P<0.05）及78条KEGG信号通路（P<0.05）。结论 IL-6、INS、VEGFA、AKT1等核心靶点作用于乙肝通路、类风湿关节炎通路、TNF通路、IBD通路调控炎症反应及糖脂代谢等生物过程,使骨质疏松及非酒精性脂肪肝互相影响,为临床治疗两种疾病提供了较为科学的理论基础。     

I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling

Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I‐branching N‐acetylglucosaminyltransferase (GCNT2) converts linear i‐antigen to I‐branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin‐embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2‐positive cells were significantly lesser in organ‐confined disease than in that with extra‐capsular extensions, and GCNT2‐negative tumors were associated with significantly better prostate‐specific antigen‐free survival compared with GCNT2‐positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I‐antigen on the O‐glycan and glycolipid. Moreover, I‐antigen‐bearing glycolipids were subject to α5β1 integrin–fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.     

妊娠糖尿病患者血清Betatrophin、Omentin-1水平与糖脂代谢及胰岛素抵抗的相关性

目的 探讨妊娠糖尿病（GDM）患者血清Betatrophin、脂肪组织中网膜素１（Omentin-1）水平变化特点,分析其与糖脂代谢和胰岛素抵抗的相关性。方法 选择2019年5月—2020年8月承德市中心医院妇产科接诊的179例孕妇。采用酶联免疫吸附试验检测所有孕妇妊娠10～14周血清Betatrophin、Omentin-1水平。所有孕妇妊娠24～26周进行口服葡萄糖糖耐量试验（OGTT）,其中,119例被诊断为GDM（GDM组）,60例血糖水平正常的孕妇为对照组。检测两组孕妇的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FBG）、空腹胰岛素（FINS）及糖化血红蛋白（HbA1c）水平。采用稳态模型计算胰岛素抵抗指数（HOMA-IR）。分析Betatrophin、Omentin-1与GDM患者糖脂代谢指标的相关性。多元线性逐步回归分析GDM患者HOMA-IR的影响因素。结果 GDM组孕前体重指数（BMI）、FBG、FINS、HOMA-IR、HbA1c、TC、LDL-C、Betatrophin水平高于对照组（P <0.05）,Omentin-1水平低于对照组（P <0.05）。相关性分析结果显示GDM患者血清Betatrophin与TG（r_s =0464）、HOMA-IR（r =0.610）、LDL-C（r =0.512）呈正相关（均P <0.05）,Omentin-1水平与孕前BMI（r_s =-0.304）、LDL-C（r =-0.543）、FBG（r =-0.475）、FINS（r =-0.435）、HOMA-IR（r =-0.576）呈负相关（均P <0.05）。多元线性逐步回归分析结果显示TG、LDL-C、Betatrophin、Omentin-1是GDM患者HOMA-IR的影响因素（P <0.05）。结论 GDM患者血清Betatrophin水平升高,Omentin-1水平降低,Betatrophin、Omentin-1均与GDM患者糖脂代谢、胰岛素抵抗有关。     

不同糖耐量人群血清kisspeptin水平与胰岛β细胞功能及糖脂代谢相关因子的相关性

目的检测不同糖耐量人群体内血清kisspeptin水平,分析探讨kisspeptin与胰岛β细胞功能状态及糖脂代谢相关因子的相关性。方法选取2018年1月—2018年12月于本院门诊就诊者120人为研究对象,根据葡萄糖耐量实验(OGTT)结果分为新诊断2型糖尿病患者51例(T2DM组)、糖耐量异常者30例(IGT组)和正常糖耐量者39例(NGT组),进行糖脂代谢指标测定,ELISA法检测血清kisspeptin水平。 结果NGT组、IGR组和T2DM组血清kisspeptin水平依次升高(P＜0.05),与WHR、SBP、FBG、HOMA-IR、HbA1c和2hPG呈正相关(P＜0.05);与体质量指数(BMI)、HOMA-β和TG呈负相关(P＜0.05)。多元逐步回归分析结果显示,FBG和BMI是血清kisspeptin水平的影响因素,kisspeptin水平的高低与糖脂代谢紊乱程度有预测作用。结论不同糖耐量人群之间血清Kisspeptin水平存在明显差异,Kisspeptin水平与FBG和BMI相关,监测kisspeptin水平变化可能可以作为评判糖耐量异常的指标。