罗格列酮对2型糖尿病合并急性冠脉综合征患者血清TGF—β1及IL-1β的影响

目的：观察罗格列酮对2型糖尿病合并急性冠脉综合征患者血清转化生长因子-β1（TGF—β1）及白细胞介素-1β（IL-1β）的影响。方法：116例2型糖尿病合并急性冠脉综合征患者,随机分为罗格列酮治疗组（n=58）和常规治疗组（n=58）。检测两组患者治疗前后空腹血糖、血脂及血清TGF-β1、IL-1β的变化。结果：治疗前两组患者空腹血糖、血脂及血清TGF-β1、IL-1β的水平无显著差异（P〉0．05）;治疗4月后,两组患者空腹血糖、血脂无显著差异,血清IL-1β较治疗前下降（P〈0．01）,罗格列酮组较常规治疗组下降明显,两组间差异显著（P〈0．05）;治疗后血清TGF—β1较治疗前上升（P〈0．05）,罗格列酮组与常规治疗组比较,差异显著（P〈0．05）。结论：罗格列酮能调控糖尿病合并急性冠脉综合征患者炎症介质和抗炎因子的分泌,可能具有改善动脉粥样硬化的作用。     

Old and new generation lipid mediators in acute inflammation and resolution

Originally regarded as just membrane constituents and energy storing molecules, lipids are now recognised as potent signalling molecules that regulate a multitude of cellular responses via receptor-mediated pathways, including cell growth and death, and inflammation/infection. Derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), each lipid displays unique properties, thus making their role in inflammation distinct from that of other lipids derived from the same PUFA. The diversity of their actions arises because such metabolites are synthesised via discrete enzymatic pathways and because they elicit their response via different receptors. This review will collate the bioactive lipid research to date and summarise the findings in terms of the major pathways involved in their biosynthesis and their role in inflammation and its resolution. It will include lipids derived from AA (prostanoids, leukotrienes, 5-oxo-6,8,11,14-eicosatetraenoic acid, lipoxins and epoxyeicosatrienoic acids), EPA (E-series resolvins), and DHA (D-series resolvins, protectins and maresins).     

S-腺苷甲硫氨酸代谢途径相关基因在小麦水分胁迫中的表达

以小麦品种‘晋麦47’为材料,利用半定量RT-PCR方法,对S-腺苷甲硫氨酸代谢途径中的S-腺苷甲硫氨酸合成酶(SAMS)基因、S-腺苷甲硫氨酸脱羧酶(SAMDC)基因和γ-谷氨酰半胱氨酸合成酶(-γECS)基因在正常供水、PEG-6000模拟水分胁迫和复水过程中小麦叶片的表达模式进行了分析。结果表明,3个基因在正常生长情况下有一定量的表达,SAMS和SAMDC基因在水分胁迫早期(PEG-6000胁迫6、12、244、8 h)上调表达,水分胁迫后期(PEG-6000胁迫75 h)表达量下降;复水后3~6 h上调表达,复水9 h后表达量下调至对照水平。-γECS基因在水分胁迫阶段呈上调表达,复水后表达量下调至对照水平。可见,小麦SAMS、SAMDC和-γECS基因的表达都受水分胁迫诱导,同时,SAMS与SAMDC基因还参与水分胁迫后的复水调节,说明S-腺苷甲硫氨酸代谢途径在小麦抗旱节水中具有重要作用。     

Protease-Activated Receptor�C1 Expression in Rat Microglia after Trimethyltin Treatment

In the nervous system, protease-activated receptors (PARs), which are activated by thrombin and other extracellular proteases, are expressed widely at both neuronal and glial levels and have been shown to be involved in several brain pathologies. As far as the glial receptors are concerned, previous experiments performed in rat hippocampus showed that expression of PAR-1, the prototypic member of the PAR family, increased in astrocytes both in vivo and in vitro following treatment with trimethyltin (TMT). TMT is an organotin compound that induces severe hippocampal neurodegeneration associated with astrocyte and microglia activation. In the present experiments, the authors extended their investigation to microglial cells. In particular, by 7 days following TMT intoxication in vivo, confocal immunofluorescence revealed an evident PAR-1-related specific immunoreactivity in OX-42-positive microglial cells of the CA3 and hilus hippocampal regions. In line with the in vivo results, when primary rat microglial cells were treated in vitro with TMT, a strong upregulation of PAR-1 was observed by immunocytochemistry and Western blot analysis. These data provide further evidence that PAR-1 may be involved in microglial response to brain damage.     

The G protein-coupled cannabinoid-1 (CB1) receptor of mammalian brain: Inhibition by phthalate esters in vitro

This research examines the in vitro interaction of phthalate diesters and monoesters with the G protein-coupled cannabinoid 1 (CB₁) receptor, a presynaptic complex involved in the regulation of synaptic activity in mammalian brain. The diesters, n-butylbenzylphthalate (nBBP), di-n-hexylphthalate (DnHP), di-n-butylphthalate (DnBP), di-2-ethylhexylphthalate (DEHP), di-isooctylphthalate (DiOP) and di-n-octylphthalate (DnOP) inhibited the specific binding of the CB₁ receptor agonist [³H]CP-55940 to mouse whole brain membranes at micromolar concentrations (IC₅₀s: nBBP 27.4 μM; DnHP 33.9 μM; DnBP 45.9 μM; DEHP 47.4 μM; DiOP 55.4 μM; DnOP 75.2 μM). DnHP, DnBP and nBBP achieved full (or close to full) blockade of [³H]CP-55940 binding, whereas DEHP, DiOP and DnOP produced partial (55-70%) inhibition. Binding experiments with phenylmethane-sulfonylfluoride (PMSF) indicated that the ester linkages of nBBP and DnBP remain intact during assay. The monoesters mono-2-ethylhexylphthalate (M2EHP) and mono-isohexylphthalate (MiHP) failed to reach IC₅₀ at 150 μM and mono-n-butylphthalate (MnBP) was inactive. Inhibitory potencies in the [³H]CP-55940 binding assay were positively correlated with inhibition of CB₁ receptor agonist-stimulated binding of [³⁵S]GTPγS to the G protein, demonstrating that phthalates cause functional impairment of this complex. DnBP, nBBP and DEHP also inhibited binding of [³H]SR141716A, whereas inhibition with MiHP was comparatively weak and MnBP had no effect. Equilibrium binding experiments with [³H]SR141716A showed that phthalates reduce the B_max of radioligand without changing its K_d. DnBP and nBBP also rapidly enhanced the dissociation of [³H]SR141716A. Our data are consistent with an allosteric mechanism for inhibition, with phthalates acting as relatively low affinity antagonists of CB₁ receptors and cannabinoid agonist-dependent activation of the G-protein. Further studies are warranted, since some phthalate esters may have potential to modify CB₁ receptor-dependent behavioral and physiological outcomes in the whole animal.     

PPARγ与c/EBPα基因在苏太猪不同组织中的表达水平探究

为探究PPARγ与c/EBPα基因在苏太猪不同组织中的表达与脂肪沉积的关系,本实验以10月龄苏太猪为研究对象,运用实时荧光定量PCR (q RT-PCR)技术检测PPARγ与c/EBPα基因mRNA在苏太猪心、肝、脾、肺、肾、胃、背最长肌和皮下脂肪8个组织中的表达水平。结果表明,PPARγ与c/EBPα基因在苏太猪的8个组织中均有不同程度的表达,其中,PPARγ基因在苏太猪脾脏组织中的表达量最高,皮下脂肪中的表达水平仅次于脾;以背最长肌中PPARγ基因的相对表达量作对比,背最长肌与脾、肺和皮下脂肪的相对表达差异极显著(p<0.01),其余为差异不显著(p>0.05),表达量高低顺序为脾>皮下脂肪>肺>心>胃>肾>肝>背最长肌;c/EBPα基因在苏太猪的皮下脂肪的表达量最高,以背最长肌中c/EBPα基因的相对表达量作对比,在肝、脾、皮下脂肪组织中表达差异极显著(p<0.01),肺的相对表达差异显著(p<0.05),其余组织中差异不显著(p>0.05),表达量的高低顺序为皮下脂肪>肝>脾>肺>肾>心>胃>背最长肌。两基因在各组织中表达趋势趋于一致。试验结果表明PPARγ和c/EBPα基因可能对猪脂肪沉积有重要影响。     

Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients

Virologica Sinica - Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have...     

鉴定单克隆抗体识别蛋白质抗原表位方法的建立

为了建立鉴定治疗性单克隆抗体识别蛋白质抗原表位的方法,选择程序死亡受体-1 (PD-1) 作为目的蛋白。基于丙氨酸扫描策略,建立了定点突变技术和哺乳动物细胞表达系统相结合的抗原突变体快速表达方法,确定了真核表达元件扩增和细胞转染表达的条件。共表达了150个PD-1蛋白突变体,鉴定了这些突变体与抗PD-1抗体帕博利珠单抗的结合能力。根据蛋白突变体与抗体的结合力并结合蛋白结构分析确定了帕博利珠单抗的抗原表位,与已报道的基于晶体结构的抗原表位高度一致,表明本方法操作简单、准确性高,可用于治疗性单克隆抗体的抗原表位作图。