C-反应蛋白与肥胖大鼠胰岛素抵抗相关性

目的探讨饮食诱导肥胖大鼠血清C-反应蛋白(CRP)与胰岛素抵抗(IR)的关系。方法30只雄性Wistar大鼠随机分成对照组和高脂组,分别喂基础饲料和高脂饲料12周,测定12周末空腹血糖(FPG)、空腹胰岛素(FINS)、血清CRP、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,以胰岛素敏感指数(ISI)判定机体胰岛素抵抗(IR)状态。结果12周末,高脂组大鼠血清CRP、TNF-αI、L-6水平分别为(2.933±1.039)mg/L,(2.029±0.152)μg/L,(130.32±23.28)ng/L,均高于对照组(P<0.05),而且TNF-αI、L-6分别与CRP呈正相关(P<0.05),CRP与ISI呈负相关(P<0.05)。结论CRP可能涉及肥胖及肥胖相关的IR。     

胰岛素抵抗与体质量指数对PCOS妇女脂代谢及性激素的影响

目的 探讨胰岛素抵抗(IR)与体质指数(BMI)对多囊卵巢综合征(PCOS)妇女脂代谢与性激素的影响.方法 选取2015年7月至2016年12月在海南医学院第二附属医院东湖妇产科就诊的198例PCOS患者,根据体质指数与胰岛素抵抗指数分为胰岛素抵抗+肥胖组(A组)、胰岛素抵抗+非肥胖组(B组)、非胰岛素抵抗+肥胖组(C组)和非胰岛素抵抗+非肥胖组(D组),对比四组患者的卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E2)、睾酮(T)、性激素结合蛋白(SHBG)及脂代谢指标.结果 四组患者BMI、腰围、腰臀比(WHR)、胰岛素抵抗指数(HOMA-IR)比较均有统计学差异(F值分别为2.657、3.024、2.997、3.223,均P<0.05),A组和C组BMI、腰围、WHR均显著高于B组和D组(t=2.446~2.780,均P<0.05),A组和B组BMI、腰围、W HR均显著高于C组和D组(t=2.409~3.127,均P<0.05).四组患者血清FSH、E2、T比较无显著性差异(F值分别为0.790、1.030、1.103,均P>0.05),LH和SHBG比较有显著性差异(F值分别为3.112、2.579,均P<0.05),A组LH水平最高,D组SHBG水平最高.四组患者总胆固醇(TC)、甘油三酯(TG)比较有显著性差异(F值分别为2.908、2.557,均P<0.05),进一步每两组之间比较发现,A组和B组均显著高于C组和D组(t=3.408~2.676,均P<0.05),A组和B组之间、C组和D组之间比较无显著性差异(t值分别为0.788、0.457,均P>0.05).四组患者高密度脂蛋白(HDL)、低密度脂蛋白(LDL)比较无显著性差异(F值分别为1.009、1.243,均P>0.05).结论 患有胰岛素抵抗及肥胖患者有更严重的脂代谢异常及性激素分泌紊乱,需要积极干预治疗.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

三个新的芳酯基取代单糖的波谱特征

目的:研究新的天然产物芳酯基取代单糖的波谱特征.方法:从光苞紫菊(Notoseris psilolopis Shih)中分离得到三个芳酯基取代单糖化合物,用红外光谱、质谱、核磁共振氢谱与碳谱进行测试.结果:三个新化合物的红外光谱3400 cm-1处有典型的羟基吸收,1730～1724 cm-1有典型的酯基吸收,1600～1400 cm-1有苯环的骨架吸收;质谱上应采用快原子轰击质谱(FAB)、电喷雾质谱(ESI)等软电离技术确定它们的分子量和分子式;由于互变异构体的存在,核磁共振谱有特征较明显的异头氢和异头碳信号.结论:归纳三个新的化合物的波谱特征.     

丹参对高原大鼠肝缺血再灌注损伤的保护作用

目的:探讨丹参(SM)对大鼠缺血再灌注(IR)肝细胞凋亡和凋亡抑制基因bcl-2表达的影响。方法:用TUNEL法观察IR后的肝细胞凋亡,并用免疫组织化学法检测相关基因表达变化;以丹参注射液干预IR的大鼠模型,观察了丹参对IR后肝细胞凋亡的作用,并与平原对照比较。结果:IR后肝细胞有典型的凋亡特征,与丹参组比较肝细胞的凋亡率有明显差异(P<0.01)。IR组bcl-2表达下调,而丹参组的表达量明显增加(P<0.01)。上述基因表达变化与病理改变一致,但与平原比较,高原较平原重。结论:丹参能减少大鼠IR肝细胞凋亡,并能上调IR肝细胞凋亡抑制基因的蛋白表达。后者可能是丹参抑制IR肝细胞凋亡的机制之一。     

灵香草及珍珠菜属4种形近品红外快速鉴别

目的：建立一种中红外光谱（FTIR）与二阶导数谱相结合,对灵香草及4种珍珠菜属形近品进行快速鉴别的方法。方法：根据其所含化学成分的不同在中红外光谱和高分辨率的二阶导数谱反映出的显著差异,对珍珠菜属5种外观相似的有香味品种进行区别、鉴定。结果：根据5个品种所含组分的不同在中红外、二阶导数上反映出来的差异,得到灵香草的二阶导数光谱指纹峰为3698、3624、3528、2920、2851、1746（宽,双峰）、1696、1658、1368（双峰）、1316（双峰）、1077、1030和1008（等强度）、834cm-1和779（等强度）、535cm-1和471cm-1（等强度）。结论：中红外光谱和二阶导数谱相结合可快速有效地鉴别灵香草及其4种珍珠菜同属易混品,该法快速、准确、重现性好,为中药材的快速鉴别提供了一种新的方法和手段。     

SP免疫阳性神经纤维在人胃癌组织中分布的实验研究(四)

目的研究人胃癌组织内SP阳性神经纤维的分布。方法人的胃癌组织固定后切片，进行抗SP硫酸镍胺加强ABC组化染色。光镜下观察胃癌组织内SP免疫组化阳性神经纤维的分布。结果在所有胃癌组织标本内均发现有较多的SP免疫反应阳性神经纤维，神经纤维的由周边组织向癌巢内方向延伸，并不断分支较多细小神经纤维穿行于癌细胞间。在癌巢内神经分布紊乱．无明显的层次，明显不同于正常的胃壁组织神经生长规则分布于黏膜下和平滑肌层的结构特点。结论胃癌组织内有神经纤维的存在，SP阳性纤维分布于胃癌细胞间．提示这些神经纤维的存在可能对胃癌细胞的某些生物学特性起调控作用：     

原发性高血压的抗胰岛素机制的研究

\t\t\t\t\t  目的  \t\t\t\t\t探讨胰岛素自身抗体(IAA)含量与原发性高血压(EHT)的关系, 揭示胰岛素抵抗(IR)与EHT的发生机制。\t\t\t\t\t  方法  \t\t\t\t\t在北票市600名60岁以下的中小学教师中筛选出EHT58人(排除继发性高血压、原发性肾脏疾患和糖尿病)作为观察组; 从该人群中随机抽取血压正常、无肝肾疾患及糖尿病者33人作为对照组.用定量方法检测IAA含量, 经χ²检验、非条件Logistic分析揭示IAA与EHT的关系。\t\t\t\t\t  结果  \t\t\t\t\tEHT组IAA水平比例明显高于对照组, EHT组分别为10.34%, 44.83%, 44.83%, 对照组分别为33.33%, 48.49%, 18.18%, 经χ²检验有显著性差异(P < 0.05);在不同因素下, 在因素水平较低组均有显著性差异(P < 0.05), 且因素的不同水平下IAA与EHT间存在剂量-反应关系; 经非条件Logistic分析, 最终进入模型的有家族史、胰岛素(IN)、IAA。\t\t\t\t\t  结论  \t\t\t\t\t结果提示IAA与EHT的发生有联系, 多因素分析提示IAA可能是EHT的危险因素; IAA与EHT发生联系与年龄、总胆固醇(CHO)、血糖(GLU)、IN有关。     

Solubility Properties of Racemic Praziquantel and Its Enantiomers

ABSTRACT

The purpose of this study was to characterize the solubility and thermodynamic properties of the optical isomers of the anti-schistosomal drug, praziquantel (PZQ) and to compare these properties to those of the racemic product used in commercial preparations (Biltricide®, generic drugs), The crystalline enantiomers of PZQ exhibited different thermal properties than the racemic drug. The melting points and the enthalpies of fusion obtained from the differential scanning calorimetry (DSC) scans were nearly identical between the isomers and were substantially lower than those of racemic PZQ [(±)-PZQ]. The DSC results indicate that (±)-PZQ is a racemic compound and not a racemic mixture. This was confirmed by powder x-ray diffraction analysis and the IR spectra. The 30° decrease in the melting point was reflected in increased solubility of the enantiomers, which amounted to twice that of the racemic PZQ. The behavior of the isomers in the presence of β-cyclodextrin (β-CD) was studied in water at 37°C. The solubility data (phase solubility diagrams) were linear for up to the highest concentration of added β-CD investigated. The apparent stability constants determined from the phase solubility diagrams showed that both the (+) and (-) enantiomers as well as (&[±)-PZQ exhibited moderate affinity to form a 1:1 complex in solution with β-CD. The findings of this study may be of importance when efforts are considered to improve pharmaceutical formulation of this anti-schistosomal drug.     

Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.