New insights on P2X purinoceptors

Significant advances in understanding of P_2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P_2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P_2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P_2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P_2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P_2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P_2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P_2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P_2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents.     

High-resolution CT Findings Suggest a Developmental Abnormality Underlying Superior Canal Dehiscence Syndrome

Objective--Patients with superior canal dehiscence (SCD) syndrome experience vertigo and oscillopsia with loud sounds and/or stimuli that result in changes in middle ear or intracranial pressure. Findings on temporal bone CT were analyzed to determine if a developmental abnormality is associated with the syndrome. Material and methods--Temporal bone CT scans [0.5 mm collimation and projections into the superior semicircular canal (SC) plane] were used to compare the bone overlying the SC in patients with SCD syndrome (20 unilateral, 7 bilateral) and in 88 patients without SCD syndrome who had undergone temporal bone CT for evaluation of other otologic disorders (controls). Results--The thickness of bone overlying the SC in the controls measured 0.67±0.38 mm (mean±SD). For individual control subjects, the thickness of bone on one side was correlated with that on the other side (r=0.43; p&;lt;0.0001). The thickness of bone overlying the SC on the intact side in patients with unilateral dehiscence measured 0.31±0.23 mm, and was thinner than that noted in the controls (p&;lt;0.0001). Conclusions--These findings support the notion that there is a developmental abnormality underlying SCD syndrome. When dehiscence is found on one side, the contralateral side is likely to be thin.     

Effects of Matrine on JAK-STAT Signaling Transduction Pathways in Bleomycin-Induced Pulmonary Fibrosis

The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung tissues were observed using hematoxylin-eosin staining. The expression of JAK, STAT1, and STAT3 was observed using immunohistochemistry and then determined using real-time polymerase chain reaction. Alveolitis and PF significantly improved in the treatment group compared with the model group (P < 0.05). The expression of JAK, STAT1, and STAT3 in the model group increased at day 7, peaked at day 14 and then decreased, but the expression was still higher than that in the control group at day 28 (P < 0.05). The three indices in the treatment group were significantly lower than those in the model group at any detection time point (P < 0.05). PF causes high expression of JAK, STAT1, and STAT3. Matrine exerts an anti-PF effect by inhibiting the JAK-STAT signaling transduction pathways.     

Growth Factors in Intervertebral Disc Homeostasis

Intervertebral disc degeneration is a complex age-related pathology associated with back pain. Research on the growth factors that regulate disc homeostasis is of critical importance for understanding the basis of the disease. Here we summarize the data on the expression and function of various growth factors in the disc from in vivo and in vitro studies, as well as on their alterations during degeneration and ageing. Such studies are becoming more crucial in the prospect of clinical application of growth factors for the treatment of disc degeneration.     

Estrogen Activation of G-Protein–Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes

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PI3K－Akt 信号通路在内皮祖细胞移植减轻大鼠缺血再灌注肾损伤中的作用

目的探讨磷脂酰肌醇－3－激酶－丝氨酸／苏氨酸激酶（ PI3K－Akt）信号通路在内皮祖细胞（ EPC）移植减轻大鼠缺血再灌注肾损伤中的作用。方法抽取大鼠外周血,采用密度梯度离心的方法分离、培养内皮组细胞。22只雄性SD大鼠随机分为正常对照组、缺血再灌注（ I／R）组、EPCs移植组3组,分别于术后第1 d收获所有大鼠肾脏标本和血标本。流式细胞仪及细胞免疫荧光鉴定 EPC 表面标志（ CD34／VEGFR－2）;测定血标本尿素氮和肌酐值;行western bolt检测各组大鼠p－AKT蛋白的表达情况。结果与正常对照组比较,其余各组血肌酐及尿素氮均升高,I／R组、EPC组肾脏p－Akt表达上调（ P ＜0．05）;与I／R组比较,EPC组的肌酐及尿素氮降低,p－Akt表达上调（ P ＜0．05）。结论 EPC移植可能通过激活PI3K－Akt信号通路减轻大鼠缺血再灌注肾损伤。     

生物机械力对血管重构的影响及机制

生物机械力的作用到处存在,在人的生命过程中对发育、生长、疾病等都起到重要作用。生物机械力是如何作用于机体并引发一系列生理病理的变化一直是人们关注的焦点。相关研究在许多领域已经取得较好的进展,在心血管研究方面尤其如此。例如,人们初步认识到血压升高或血管构筑改变导致血流动力学改变既可为引起血管疾病的始动因素,又可为维持或加速疾病变化的终极成分,并成为比任何生长因子或致病多肽对血管结构和功能影响更加明显的独立危险因子。本文将结合我们自己的部分工作,就机械力对血管结构、功能影响及相关信号转导机制做一个简要介绍。     

脑缺血后自噬的信号转导通路

脑缺血后自噬可被激活,且参与到缺血性脑损伤的发生和发展过程中,因此自噬相关信号转导通路的研究有可能为缺血性脑损伤提供新的治疗靶点。文章就脑缺血后自噬的信号转导通路进行了综述。