The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.     

A bromine-catalysis-synthesized poly(3,4-ethylenedioxythiophene)/graphitic carbon nitride electrochemical sensor for heavy metal ion determination

In this paper, poly(3,4-ethylenedioxythiophene)/graphitic carbon nitride (PEDOT/g-C₃N₄) composites were prepared by the bromine catalysed polymerization (BCP) method with varying weight ratios of monomer to g-C₃N₄. For comparison, solid-state polymerization (SSP) and metal oxidative polymerization (MOP) methods were also used for the synthesis of PEDOT/g-C₃N₄ composites. Electrochemical determination of heavy metal ions (Cd²⁺ and Pb²⁺) was carried out by differential pulse voltammetry (DPV) on composite-modified glass carbon electrodes (GCEs), which were prepared by different methods. The obtained composites were analysed by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible absorption spectroscopy (UV-vis), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results showed that the bromine catalysed polymerization (BCP) method is an effective way to prepare the PEDOT/g-C₃N₄ composite, and the combination of PEDOT with g-C₃N₄ can improve the electrochemical activity of electrode materials. And, the composite from the BCP method modified electrode (PEDOT/10 wt% g-C₃N₄/GCE) exhibited the widest linear responses for Cd²⁺ and Pb²⁺, ranging from 0.06–12 μM and 0.04–11.6 μM with detection limits (S/N = 3) of 0.0014 μM and 0.00421 μM, respectively.

The PEDOT/g-C₃N₄ composite prepared by a Br₂-catalyzed polymerization method exhibited the widest linear electrochemical responses for Cd²⁺ and Pb²⁺.     

细粒棘球蚴囊液对体外培养小鼠脾细胞Foxp3及Smad4基因表达的影响

目的观察细粒棘球蚴囊液对体外培养BABL/c小鼠脾脏细胞中调节性T细胞(Treg细胞)相对特异分子Foxp3(叉头蛋白3)及TGF-β1(转化生长因子-β1)下游信号通路Smad4表达的影响。方法以BABL/c小鼠作为脾细胞供者,用研磨法分离脾脏细胞,随机分为实验组(与细粒棘球蚴囊液共同培养)和对照组,取1×105个细胞接种于96孔板上,分别在1、3、6和12 h提取RNA,实时荧光定量PCR(qRT-PCR)检测Foxp3以及Smad4的基因表达。结果 qRT-PCR显示,细粒棘球蚴囊液处理1、3和12 h,实验组Foxp3表达量分别为4.577±0.317、8.517±0.978和7.406±0.822,对照组分别为9.274±0.451、3.297±0.408和2.464±0.328,差异均有统计学意义(P<0.05);细粒棘球蚴囊液处理1 h和12 h,实验组Smad4表达量分别为3.862±1.417和1.690±0.248,对照组分别为1.689±0.221和3.600±1.081,差异有统计学意义(P<0.05),且Foxp3与Smad4二者之间存在负相关(r=-0.991,P<0.05)。结论...     

囊型包虫病患者外周血单核细胞诱导的树突状细胞形态及表型特点

目的研究囊型包虫病患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)体外诱导的树突状细胞(dendritic cell,DC)的形态及其细胞表型特点。方法囊型包虫病患者组(cystic echinococcosis,CE)15例,健康志愿者对照组(healthy donor,HD)15例,采外周血(肝素抗凝)分离单个核细胞后贴壁培养,施加重组细胞因子培养6d,诱导成DC,采用倒置显微镜和扫描电镜观察细胞形态,流式细胞术检测CD86、HLA-DR、CD1a、CD80的表达情况。结果与HD组比较,CE组PBMC诱导的DC表面的树突状突起较少,且细胞表面的CD86、HLA-DR、CD1a、CD80表达降低(P0.05)。结论CE组患者PBMC诱导的DC形态不典型,表面分子的表达降低,细胞活力降低,对T细胞的刺激能力减弱。     

异常黑胆质型抑郁症与非异常黑胆质型抑郁症神经内分泌功能的比较研究

目的 观察异常黑胆质型与非异常黑胆质型抑郁症患者神经内分泌功能,为抑郁症的维医异常体液辨证分型和个体化防治提供理论依据.方法 根据维吾尔医学体液论对确诊为抑郁症的201例患者进行异常体液辨证分型,分为异常黑胆质型抑郁症组(107例)和非异常黑胆质型抑郁症组(94例)两组;两组患者都处于重度抑郁状态,采用放射免疫法分别检测两组抑郁症患者血清或血浆肾上腺素(EP)、多巴胺(DA)、去甲肾上腺素(NE)、促肾上腺皮质激素(ACTH)、皮质醇(CORT)、5-羟色胺(5-HT)和促肾上腺皮质激素释放激素(CRH)含量.结果 异常黑胆质型和非异常黑胆质型抑郁症患者血清或血浆EP、NE、CORT、CRH、5-HT含量相比差异均有统计学意义(P<0.05),异常黑胆质型抑郁症患者EP、NE、5-HT含量明显低于非异常黑胆质型抑郁症患者(P<0.05),异常黑胆质型抑郁症患者CORT和CRH含量明显高于非异常黑胆质型抑郁症患者(P<0.05),两组DA、ACTH含量差异无统计学意义(P>0.05).结论 异常黑胆质型与非异常黑胆质型抑郁症患者神经内分泌功能之间存在差异.提示,抑郁症的维医体液辨证分型与神经内分泌功能之间具有密切联系.     

血清胱抑素C和尿微量白蛋白/肌酐比值联合检测对高血压早期肾损害的诊断价值

目的 探讨血清胱抑素（Cyst-C）、尿微量白蛋白/肌酐（UmAlb/UCr）对高血压患者早期肾损害的诊断价值.方法 根据肾动态显像结果将85例原发性高血压患者分为早期肾功能损害组（A组）32例和单纯高血压组（B组）53例,并选取健康体检者50例为对照组,采用酶联免疫法测定各组Cyst-C、UmAlb/UCr、血清尿素氮（BUN）、血清肌酐（Scr）含量.结果 与对照组相比,A组及B组Cyst-C、UmAlb/UCr水平显著升高,B组则高于A组,差异有统计学意义（P＜0.05）,而三组BUN、Scr水平比较差异无统计学意义（P＞0.05）.随着高血压分级的增加,Cyst-C、UmAlb/UCr水平显著上升,其中Ⅲ级组患者显著高于Ⅰ级组及Ⅱ级组,差异有统计学意义（P.＜0.05）.Cyst-C灵敏性、特异性、准确性分别为81.6％、82.3％、69.2％,UmAlb/UCr灵敏性、特异性、准确性分别为84.5％、83.4％、76.9％,而UmAlb/UCr＋Cyst-C灵敏性、特异性、准确性分别为93.2％、91.3％、92.3％.B组Cyst-C与UmAlb/UC联合检测阳性率显著高于单纯UmAlb/UCr或Cyst-C检测,差异有统计学意义（P＜0.05）.结论 Cyst-C与UmAlb/UC联合检测有助于高血压患者早期肾损害的诊断.     

新疆一枝蒿提取物保肝作用的实验研究

目的 :探讨新疆一枝蒿提取物 (ARE)对化学性肝损伤及免疫性肝炎的保护和治疗作用。方法 :采用卡介苗 (BCG)加脂多糖 (LPS)引起的小鼠免疫性肝炎模型及四氯化碳和D 氨基半乳糖致小鼠、大鼠急性肝损伤模型 ,观察ARE对免疫性肝炎的预防和治疗作用及对化学性肝损伤的保护作用。结果 :ARE大剂量能明显降低免疫性肝炎小鼠血清谷丙转氨酶 (ALT)水平 (P <0 0 5 ) ,ARE各种剂量皆能降低四氯化碳致肝损伤小鼠和大鼠血清ALT(P <0 0 1) ,降低D 氨基半乳糖致肝损伤小鼠血清ALT(P <0 0 5 )。结论 :ARE具有明显的保护化学性肝损伤及治疗免疫性肝炎的功能 ,但对免疫性肝炎无预防作用     

Genistein对人鼻咽癌细胞系CNE抑制增殖和促进凋亡的研究

鼻咽癌是头颈肿瘤中具有鲜明流行病学、组织病理学、临床和治疗学特征的一种肿瘤。研究表明癌细胞的增殖活性是影响鼻咽癌生长进展的主导因素，肿瘤细胞的增殖活性与肿瘤的生物学行为与预后密切相关。Genistein（4，5，7-三羟基异黄酮，又名金雀异黄素）是一种广谱的蛋白酪氨酸激酶（protein tyrosine kinase，PTK）抑制剂。[第一段]