Leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the α,β-unsaturated ketone of an aryl propionic acid non-steroidal anti-inflammatory agent CS-670

CS-670 is a non-steroidal anti-inflammatory agent with an α,β-unsaturated ketone structure. It exerts its pharmacological activity after being transformed to the active metabolite (2S,1′R,2′S)-trans-alcohol. Two consecutive reductions are needed for the formation of the active metabolite, reduction of the double-bond of the α,β-unsaturated ketone moiety, followed by reduction of the resulting saturated ketone. The objective of the current study was to identify the enzyme responsible for reduction of the double-bond. An enzyme purified from rat liver cytosol as a single band on sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was analysed by a Mascot database search of nano-LC tandem mass spectrometry (MS/MS) data and the enzyme was identified as 2-alkenal reductase (EC 1.3.1.74), which is known as an β-nicotinamide adenine dinucleotide phosphate (NADPH)-dependent alkenal/one oxidoreductase and has a role for leukotriene B₄ 12-hydroxydehydrogenase/15-ketoprostaglandinΔ13-reductase (LTB₄ 12-HD/PGR). The identification was confirmed by cloning LTB₄ 12-HD/PGR cDNA from rat liver, expressing it in Escherichia coli, and characterizing the properties of the enzyme. The identity was further supported by the subcellular localization in cytosol, a cofactor requirement for NADPH, substrate specificity, and substantial inhibition by 15-ketoPGF_2α, benzylideneacetophenone, indomethacin, and quercitrin. In addition to catalysing the biological reduction of eicosanoids, including prostaglandins, leukotrienes, and lipoxins, LTB₄ 12-HD/PGR was also determined to function as a xenobiotic-metabolizing enzyme.     

兰州地区静脉毒瘾者TT病毒感染情况的调查

目的：了解兰州地区静脉毒瘾者TT病毒（TTV）感染状况及其与肝功能的关系，探讨TTV的流行病学特征及其致病性。方法：采用巢式聚合酶链反应（PCR）检测血清TTV DNA，采用酶联免疫吸附实验法（ELISA）检测谷丙转氨酶（ALT）的含量。结果：（1）静脉毒瘾组TTV DNA阳性率显著高于非静脉毒瘾组和对照组（P＜0．01）。（2）静脉毒瘾者每日静脉注射毒品次数大于3次者，TTV DNA阳性率显著高于每日静脉注射毒品次数小于3次者（P＜0．01）。（3）静脉毒瘾者TTV DNA阳性伴随血清ALT水平异常，二者存在相互关系。（4）不同人群的TV DNA阳性与TTV DNA阳性的血清ALT阳性率有显著性差异（P＜0．01）。结论：（1）血液传播是TTV传播的主要途径。（2）TTV感染与ALT异常有密切的关系，可能是非甲－非庚型肝炎病的主要病源。（3）正常人群中存在TTV感染者，类似HBsAg的所谓“慢性携带状态”。     

Conservation strategy for Pelargonium sidoides DC: Phenolic profile and pharmacological activity of acclimatized plants derived from tissue culture

Ethnopharmacological relevance

Pelargonium sidoides DC (Geraniaceae), a popular medicinal plant used in folk medicine in the treatment of respiratory-related infections has gained international prominence due to its usage in several herbal formulations. This has led to high demand and the subsequent decimation of wild populations.

Aim of the study

Using plant tissue culture techniques, Pelargonium sidoides plants were cloned in vitro, acclimatized under greenhouse conditions and evaluated for their phytochemical content and pharmacological activity.

Methods

Phenolic content in extracts of in vitro-derived, greenhouse-acclimatized and wild Pelargonium sidoides plants were analyzed using UPLC-MS/MS. The oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity and minimum inhibitory concentration (MIC) of the extracts against bacterial and fungal strains were evaluated.

Results

Similarities in phenolic profiles were identified confirming the chemical signatures that characterize Pelargonium sidoides plants. Extracts of greenhouse-acclimatized and wild plants exhibited comparable antimicrobial and antioxidant properties.

Conclusions

Overall, the study highlights the potential of integrating plant tissue culture technologies in conservation strategies of medicinal plants. In particular, the results strongly suggest the feasibility of both large-scale cultivation and plant part substitution as alternative solutions to the current destructive overharvesting practices of wild Pelargonium sidoides populations.     

血清CEA、PG、GPDA联合检测对胃癌的诊断价值

目的 探讨癌胚抗原(CEA)、胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)、PGR(PGⅠ和PGⅡ的比值)和甘氨酰脯氨酸二肽氨基肽酶(GPDA)联合检测在胃癌诊断中的应用价值. 方法 应用化学发光法、比浊法、比色法检测78胃癌患者、46例良性胃病患者(对照组1)及50例健康人(对照组2)的血清中CEA、PGⅠ、PGR、GPDA的水平,比较组间的差异.结果 癌组患者血清GPDA、PGⅠ及PGR含量均低于胃良性病变组及健康对照组(p<0.05);而CEA含量高于胃良性病变组及健康对照组(p<0.05),对照组 1与对照组2比较差异无显著性意义(p>0.05);3项标记物联合检测胃癌的敏感性和特异性可分别达89.7%、76.1%. 结论 CEA、PGⅠ、PGR and GPDA 对胃癌具有较高的辅助诊断价值,3项联合检测有助于提高胃癌诊断的敏感性.     

赤栀黄煎剂预防实验性肝硬变发生的形态学研究

实验大白鼠分三组：肝硬化组给以四氯化碳(CCl4)等复合因素，给药组除CCl4等复合因素外，给以赤栀黄煎剂灌胃41天，正常组给予一般饮食及饮用水。结果给药组与肝硬化组相比，肝硬化形成率明显降低，肝小叶损伤区域明显缩小，肝细胞中脂滴减少，细胞核增大，RNA及核仁增多，糖原恢复，SDH、G—6—Pase活性增强。表明赤栀黄合剂能减轻CCl4等复合因素引起的肝硬变，并对其机理进行了讨论。     

植物生长调节剂对多花黄精芽体外发生过程中性状的影响

目的 研究不同植物生长调节剂组合对多花黄精芽体外发生过程中每块外植体上的平均芽数、叶片发生频率、根的自然发生率及生根外植体上的平均根数、根茎发生率等性状的影响；探索通过组织培养快速繁殖该植物的最佳途径。方法 多花黄精的不定芽切块在MS BA1．0mg／L 2，4-D0．5mg／L的培养基上可被诱导产生颗粒状愈伤组织，将该愈伤组织继代于不同植物生长调节剂组合的MS培养基上，2个月后观察并统计不同植物生长调节剂组合对各性状的影响。结果 TDZ1．5mg／L 2，4-D1．0mg／L对芽增值最有利，平均每块外植体上可长出8．6个芽；BAl．0～2．0mg／L NAA1．0～2．0mg／L促进叶片形成，95％以上的外植体长出形态正常的叶片；在BA2．0mg／L NAA1．0mg／L，的培养基上，根的自然发生率最高，达到51．9％，但不及单独生长素如NAA、IAA、TBA或2，4-D等以0．5～1．0mg／L，对根的诱导作用，后者可使90％以上的再生芽生根，且根生长繁茂；BA2．0mg／L 2，4-D1．0～2．0mg/L组合最适合根茎生长，直径大于0．5cm的根状茎超过100％。结论 多花黄精的体外快速繁殖可通过如下途径实现：TDZ1．5mg/L 2，4-D1．0mg/L诱导不定芽扩增，BA1．0～2．0mg／L NAA1．0～2．0mg/L诱导健康叶片的发育，1／2MS NAA，IAA，TBA或2，4-D0．5～1．0mg/L诱导再生芽生根；BA2．0mg/L 2，4-D1．0～2．0mg/L用于以繁殖药用器官为目的的根茎的生长。     

Genetic association and gene expression studies suggest that genetic variants in the SYNE1 and TNF genes are related to menstrual migraine

Background

Menstrual migraine (MM) encompasses pure menstrual migraine (PMM) and menstrually-related migraine (MRM). This study was aimed at investigating genetic variants that are potentially related to MM, specifically undertaking genotyping and mRNA expression analysis of the ESR1, PGR, SYNE1 and TNF genes in MM cases and non-migraine controls.

Methods

A total of 37 variants distributed across 14 genes were genotyped in 437 DNA samples (282 cases and 155 controls). In addition levels of gene expression were determined in 74 cDNA samples (41 cases and 33 controls). Association and correlation analysis were performed using Plink and RStudio.

Results

SNPs rs3093664 and rs9371601 in TNF and SYNE1 genes respectively, were significantly associated with migraine in the MM population (p = 0.008; p = 0.009 respectively). Analysis of qPCR results found no significant difference in levels of gene expression between cases and controls. However, we found a significant correlation between the expression of ESR1 and SYNE1, ESR1 and PGR and TNF and SYNE1 in samples taken during the follicular phase of the menstrual cycle.

Conclusions

Our results show that SNPs rs9371601 and rs3093664 in the SYNE1 and TNF genes respectively, are associated with MM. The present study also provides strong evidence to support the correlation of ESR1, PGR, SYNE1 and TNF gene expression in MM.     

Zearalenone exposure modulates the expression of ABC transporters and nuclear receptors in pregnant rats and fetal liver

The mycotoxin zearalenone (ZEN) is produced by a variety of Fusarium fungi and contaminates numerous cereals, fruits and vegetables. Interacting with the estrogen receptors, ZEN and reduced metabolites zearalenols cause hormonal effects in animals. Few data are available on the effects of repeated exposure to ZEN, particularly during pregnancy. The aim of our work was to assess the impact of this toxin on the expression of ABC transporters and nuclear receptors in fetal liver and pregnant rats that were exposed daily (gestation day 7-20) to 1 mg/kg ZEN. Significant variations were observed, depending on the tissue type, the tissue origin (maternal or fetal), and the time of analysis after the last exposure to ZEN (4 h or 24 h). The modulations of expression were independent of the magnitude of tissue impregnation by ZEN and its metabolites. The maternal uterus was the most sensitive tissue: Abcb1a, Abcb1b and Abcg2 mRNA and protein expressions were induced at both times, while Abcc1, Abcc3 and Esr1 mRNA and protein expressions were inhibited then induced 4 h and 24 h after exposure, respectively. In the fetal liver, Abcb1a and Esr1 protein expression was inhibited at both times, while mRNA expression was induced 24 h after the last exposure to ZEN. These results suggested that ZEN exposure could impact maternal and fetal exposure to ABC transporters substrates, and influence fetus development through nuclear receptor modulation.     

PGR基因多态性与复发性自然流产的关联性研究

目的 探讨孕酮受体基因（PGR）rs590688、rs1042838、rs11224592 3个单核苷酸位点与复发性自然流产（RSA）的关联性。方法 采用TaqMan探针基因分型方法检测并比较RSA患者（病例组212例）和正常女性（对照组197名）的PGR基因3个SNPs位点基因型及等位基因频率的分布情况。结果 PGR基因rs590688、rs1042838、rs11224592位点基因型及等位基因频率在病例组和对照组间比较,差异无统计学意义（P>0.05）;PGR基因rs590688、rs11224592;2个位点构建的GC单倍型（P<0.05）及PGR基因rs590688、rs11224592、rs1042838 3个位点构建的GCG单倍型（P<0.05）在病例组和对照组间比较,差异有统计学意义。结论 PGR基因rs590688、rs11042838、rs11224592位点的基因多态性与宁夏汉族女性RSA的易感性无关;PGR基因rs590688、rs11224592两个位点构建的GC单倍型及PGR基因rs590688、rs11224592、rs1042838 3个位点构建的GCG单倍型可能是RSA的保护性因素。