小花五味子中抗HIV活性的木脂素类化合物

目的：从小花五味子中发现具有抗HW活性的化学成分。方法：采用多种柱层析分离进行化合物的分离和纯化．通过波谱分析鉴定化合物的结构，化合物的抗HIV-1活性通过对HIV-1感染C8166细胞致细胞病变的抑制试验得到。结果：从小花五味子的茎藤部分分离得到了4个木脂素，分别鉴定为micrantherin A(1)，gomisin K3(2)，gomisin G(3)和vladinol F(4)。化舍物4具有显著的抗HIV-1活性，IC50=3.51μg／mL，选择指数为27、45。结论：化合物1为新的木脂素，化合物4的抗HIV-1活性值得进一步研究。     

Neutralization of Pseudomonas aeruginosa enzymatic activity by antibodies elicited with proteins of Larrea divaricata Cav.

Larrea divaricata Cav. (Jarilla) is a bush widely used in folk therapy for the treatment of several pathologies. Partially purified proteins of crude extract (JPCE) cross-react with proteins of Gram-negative bacteria, including Pseudomonas aeruginosa, which is an opportunistic pathogen that causes several intrahospitalary infections. This bacterium produces many proteins with enzymatic activity, including hemolysins and proteases that play a major role in acute infection caused by this bacterium. The aim of our work was to investigate if antibodies against with L. divaricata neutralize the hemolytic and proteolytic activity of P. aeruginosa. The hemolytic activity of soluble cellular proteins was inhibited 100% and extracellular proteins (EP) showed an inhibition between 44 and 95% when both bacterial fractions were treated with anti-JPCE serum. Also, in EP the neutralization was directed towards the active site of the hemolysin. When protease activity of extracellular products was tested, bands of 217, 155, 121, 47 and 27?kDa were observed in native zymograms. Neutralization between 55 and 70% of the bands of 217, 155 and 121?kDa was observed when EP were treated with anti-JPCE serum. In conclusion, our data clearly demonstrate that antibodies elicited with L. divaricata’ proteins are able to neutralize the hemolytic and proteolytic activity of P. aeruginosa cellular and extracellular proteins. Our study constitutes the first report that associates the immunogenicity of plant proteins and bacterial proteins with enzymatic activity. These findings could be relevant in the development of alternatives therapies for patients suffering intrahospitalary opportunistic infections with P. aeruginosa.     

Phytochemicals and Their Biological Activities of Plants in Tagetes L.

Tagetes L., the genus in the family Asteraceae, consists of about 30 species spread in South and Middle America as well as Mexico. More than one hundred secondary metabolites have been obtained in phytochemical investigation on the species, some of which have potent biological activities. The advances in phytochemical studies and biological activities of the plants in Tagetes L. from 1925 to 2011 are summarized in this paper.     

L型钙离子通道Cav1.3和兰尼碱受体RyR1在老龄大鼠阴茎海绵体中的表达

目的:研究L型钙离子通道(Cav1.3)及兰尼碱受体(RyR1)在老龄大鼠阴茎海绵体中的表达,为探索老龄性ED发生机制提供依据。方法:A组(2月龄)和B组(18月龄)雄性健康清洁组SD大鼠各10只,测其血清睾酮,采用RT-PCR和免疫组化方法分析两组Cav1.3和RyR1在阴茎海绵体的表达。结果:血清睾酮值在B组较A组显著下降[(1 356±424)ng/Lvs(2 744±964)ng/L,P<0.05]。免疫组化结果积分吸光度(IA)值B组中Cav1.3蛋白表达较A组显著下降(18.65±8.47vs75.48±14.28,P<0.05),B组中RyR1蛋白表达较A组显著下降(21.37±9.64vs78.23±13.57,P<0.05)。Cav1.3 mRNA在B组阴茎海绵体表达较A组显著下降(0.382±0.046vs1.137±0.415,P<0.05),RyR1 mRNA在B组阴茎海绵体表达较A组显著下降(0.146±0.053vs1.215±0.261,P<0.05)。结论:Cav1.3和RyR1在老龄性大鼠阴茎海绵体中表达的降低可能是老龄性ED的发生机制之一。     

Roles of Cav channels and AHNAK1 in T cells: the beauty and the beast

Summary:  T lymphocytes require Ca²⁺ entry though the plasma membrane for their activation and function. Recently, several routes for Ca²⁺ entry through the T-cell plasma membrane after activation have been described. These include calcium release-activated channels (CRAC), transient receptor potential (TRP) channels, and inositol-1,4,5-trisphosphate receptors (IP₃Rs). Herein we review the emergence of a fourth new route for Ca²⁺ entry, composed of Ca_v channels (also known as L-type voltage-gated calcium channels) and the scaffold protein AHNAK1 (AHNAK/desmoyokin). Both helper (CD4⁺) and killer (CD8⁺) T cells express high levels of Ca_v1 α1 subunits (α1S, α1C, α1D, and α1F) and AHNAK1 after their differentiation and require these molecules for Ca²⁺ entry during an immune response. In this article, we describe the observations and open questions that ultimately suggest the involvement of multiple consecutive routes for Ca²⁺ entry into lymphocytes, one of which may be mediated by Ca_v channels and AHNAK1.     

万寿菊全株化学成分预试

目的：探讨万寿菊花、茎叶、根中的化学成分。方法：采用试管法、薄层色谱法分别对万寿菊的花、茎叶、根的石油醚、95％乙醇、水提取液进行成分研究。结果：万寿菊花中舍有多糖、黄酮、蒽醌、氨基酸、挥发油、生物碱。万寿菊茎叶中含有多糖、黄酮、香豆素、皂苷、生物碱。万寿菊根中含有多糖、黄酮、香豆素、皂苷。结论：万寿菊全株中含有丰富的天然有效成分,具有开发利用价值。     

Roles of Cav3.2 and TRPA1 channels targeted by hydrogen sulfide in pancreatic nociceptive processing in mice with or without acute pancreatitis

Hydrogen sulfide (H₂S), formed by multiple enzymes, including cystathionine‐γ‐lyase (CSE), targets Ca_v3.2 T‐type Ca²⁺ channels (T channels) and transient receptor potential ankyrin‐1 (TRPA1), facilitating somatic pain. Pancreatitis‐related pain also appears to involve activation of T channels by H₂S formed by the upregulated CSE. Therefore, this study investigates the roles of the Ca_v3.2 isoform and/or TRPA1 in pancreatic nociception in the absence and presence of pancreatitis. In anesthetized mice, AP18, a TRPA1 inhibitor, abolished the Fos expression in the spinal dorsal horn caused by injection of a TRPA1 agonist into the pancreatic duct. As did mibefradil, a T‐channel inhibitor, in our previous report, AP18 prevented the Fos expression following ductal NaHS, an H₂S donor. In the mice with cerulein‐induced acute pancreatitis, the referred hyperalgesia was suppressed by NNC 55‐0396 (NNC), a selective T‐channel inhibitor; zinc chloride; or ascorbic acid, known to inhibit Ca_v3.2 selectively among three T‐channel isoforms; and knockdown of Ca_v3.2. In contrast, AP18 and knockdown of TRPA1 had no significant effect on the cerulein‐induced referred hyperalgesia, although they significantly potentiated the antihyperalgesic effect of NNC at a subeffective dose. TRPA1 but not Ca_v3.2 in the dorsal root ganglia was downregulated at a protein level in mice with cerulein‐induced pancreatitis. The data indicate that TRPA1 and Ca_v3.2 mediate the exogenous H₂S‐induced pancreatic nociception in naïve mice and suggest that, in the mice with pancreatitis, Ca_v3.2 targeted by H₂S primarily participates in the pancreatic pain, whereas TRPA1 is downregulated and plays a secondary role in pancreatic nociceptive signaling. © 2014 Wiley Periodicals, Inc.     

The therapeutic potential of Na+ and Ca2+ channel blockers in pain management

Chronic pain affects a large percentage of the population, representing a socio–economic burden. Current treatments are characterised by suboptimal efficacy and/or side effects that limit their use. Among several approaches to treating chronic pain, voltage-sensitive Ca²⁺ and Na⁺ channels are promising targets. This review evaluates the preclinical evidence that supports the involvement of these targets, with specific attention to those subtypes that appear more strictly correlated with pain generation and sustainment, as well as those compounds that modulate the activity of Ca²⁺ and/or Na⁺ channels that are currently in clinical development for chronic pain conditions.