新型N-取代吡咯类化合物的体外抗肿瘤活性研究

目的:研究37个新型N-取代吡咯类化合物的体外抗肿瘤活性,并探讨这些化合物的结构-活性关系。方法:运用MTT法来测试37个化合物对5种肿瘤细胞和1种正常细胞的体外细胞增殖抑制活性。结果:化合物3f活性最高,其对MGC80-3的IC50值为61.29μM。同时成功地总结了新型N-取代吡咯化合物的构效关系:(1)对于吡咯母核的3位,取代苯环上对位氯取代和对位叔丁基取代化合物的抗肿瘤活性差不多,并且没有明显的规律性。(2)对于吡咯母核的4位,取代基团的电子云密度对抗肿瘤活性的影响也没有明显的规律。(3)对于吡咯母核的1位,当3位为对叔丁基苯基取代时,其整体活性顺序为:(苄基,溴乙基)(甲基,乙基,丙基,丁基)乙烯基;当3位为对氯苯基取代时,其整体活性顺序为:(乙烯基,苄基)(甲基,乙基,丙基,丁基)。结论:为了得到更好的抗肿瘤活性化合物,吡咯母核的1号位置上应该接入苄基等大空间位阻基团、容易形成氢键的基团或者不接入任何取代基,从而为吡咯类化合物的进一步结构修饰以开发更高活性的抗肿瘤化合物提供指导。     

功能性便秘患者实施中药热敷的效果观察

目的:探讨中药热敷疗法对功能性便秘(functional constipation,FC)患者进行护理的临床效应。方法:选取50例FC患者,随机分为对照组和试验组,各25例。对照组采用常规护理与治疗,试验组在对照组的基础上采用中药热敷进行护理干预,比较两组患者症状的改善及治疗效果,并在干预前后检测血液胃动素(motilin,MTL)的浓度。结果:试验组实施干预后,治疗效果优于对照组(P0.05),对排便费力、排便不尽感、大便性状的改善及缩短排便时间亦优于对照组(P0.01);干预前两组患者MTL浓度比较无统计学意义(P0.05);干预后试验组MTL浓度上升,与干预前及对照组比较,差异有统计学意义(P0.01)。结论:中药热敷疗法能有效的改善FC患者的临床症状,提高体内胃动素的浓度,增强治疗效果。     

超声介入治疗常见妇科囊性炎症包块的疗效评价*

摘要目的：比较超声引导介入治疗盆腔脓肿、输卵管积脓、输卵管积液、包裹性积液及宫颈囊肿的临床效果,了解超声引导介入 治疗常见的妇科囊性炎症包块的临床价值。方法：选取我院妇科门诊2007 年1 月～2011 年3月收治的常见妇科囊性炎症包块共 108例,其中盆腔脓肿11 例、输卵管积脓19 例、输卵管积液43 例、盆腔包裹性积液31 例、宫颈囊肿4 例,给予超声实时引导抽囊 液、甲硝唑冲洗治疗,治疗后3 个月内复查超声评价和比较疗效。结果：盆腔脓肿、输卵管积脓、盆腔包裹性积液包块均明显缩小 (12/43)或消失(29/43),治疗有效率100%;输卵管积液包块治疗有效率95％(41/43),宫颈囊肿均痊愈。各组间比较无统计学差异 （P>0.05）。结论：超声引导介入治疗对输卵管积脓、盆腔脓肿、盆腔包裹性积液均有显著的疗效,且治疗效果无差异,值得推广应 用,代替传统的非必要的手术治疗。     

缬沙坦联合吲达帕胺治疗高血压的效果观察

目的:探讨缬沙坦和吲达帕胺治疗高血压的临床效果,为临床治疗提供可借鉴的方法。方法:选取2012年4月-2014年1月在我院接受治疗的87例高血压患者的临床资料,根据治疗方式的不同将所选患者分为缬沙坦组、吲达帕胺组和联合用药组,每组27例。缬沙坦组患者采用口服缬沙坦单药治疗,吲达帕胺组患者采用口服吲达帕胺单药治疗,联合用药组采用缬沙坦+吲达帕胺缓释片治疗。观察三组患者治疗前后的血压变化、治疗总有效率及不良反应的发生情况。结果:治疗后,三组患者的血压均不同程度降低(P0.05);联合用药组患者血压下降幅度明显高于缬沙坦单药治疗组和吲达帕胺单药治疗组,差异具有统计学意义(P0.05)。联合用药组患者治疗的总有效率明显高于缬沙坦单药治疗组和吲达帕胺单药治疗组,差异具有统计学意义(P0.05)。三组患者不良反应的发生率无显著差异(P0.05)。结论:缬沙坦胶囊与吲哒帕胺缓释片联合应用治疗高血压具有显著的临床意义,能够有效的控制患者的血压,值得推广采用。     

黄芪、何首乌、女贞子、菟丝子混合提取物对体外培养毛囊生长的影响及药理作用研究

目的:通过体内外实验探讨黄芪、何首乌、女贞子、菟丝子混合中药提取物对毛囊增殖的影响作用以及其作用机理。方法:通过体外培养的C57BL/6小鼠毛囊器官模型观察不同浓度中药提取物对毛囊生长的影响;采用MTT法测定不同浓度中药提取物对毛乳头增殖的影响;蛋白免疫印迹法(Western Blot)和ELISA检测中药提取物对毛乳头细胞分泌肝细胞生长因子(HGF)的影响。结果:中药提取物能够刺激体外培养的小鼠毛囊的生长,800μg/mL浓度的促进作用最强;160μg/mL中药提取物对毛乳头细胞的增殖作用最强,与米诺地尔、齐墩果酸阳性对照存在显著性差异(P0.05)。而且,药提取物促进了毛乳头细胞分泌HGF。结论:黄芪、何首乌、女贞子、菟丝子混合中药提取物在促进毛发生长中起到重要作用,促进毛乳头细胞增殖和分泌HGF是促进毛囊生长的可能性药理机制。     

The Prostate Basal Cell (BC) Heterogeneity and the p63-Positive BC Differentiation Spectrum in Mice

The prostate epithelium is composed of basal (BC), luminal (LEC), and neuroendocrine (NEC) cells. It is unclear how many subtypes of BCs in the prostate and which subtype of BCs contains the main stem cell niche in the adult prostate. Here we report seven BC subpopulations according to their p63, cytokeratin 14 (K14) and K5 expression patterns, including p63-positive/K14-negative/K5-negative (p63+/K14-/K5-), p63-/K14+/K5-, p63-/K14-/K5+, p63+/K14+/K5-, p63+/K14-/K5+, p63-/K14+/K5+, and p63+/K14+/K5+ BCs. We generated a p63-CreERT2 knock-in mouse line that expresses tamoxifen-inducible Cre activity in the p63-expressing cells, including the prostate BCs. We then crossbred this line with ROSA26R mice, and generated p63-CreERT2×ROSA26R bi-genic mice harboring the Cre-activated β-galactosidase reporter gene. We treated these bi-genic mice with tamoxifen to mark the p63+ BCs at different ages or under different hormonal conditions, and then traced the lineage differentiation of these genetically labeled BCs. We discovered that these p63+ BCs contain self-renewable stem cells in culture and efficiently differentiated into LECs, NECs and BCs in the postnatal, adult and re-generating mouse prostates. Therefore, BC population contains heterogeneous BCs that express different combinations of the p63, K14 and K5 differentiation markers. Because K14+ and K5+ BCs were previously shown to be extremely inefficient to produce LECs in adulthood, we propose that the p63+/K5-/K14- subpopulation of BCs contains most stem-like cells, especially in adult animals.     

Sequence-based identification of recombination spots using pseudo nucleic acid representation and recursive feature extraction by linear kernel SVM

Background

Identification of the recombination hot/cold spots is critical for understanding the mechanism of recombination as well as the genome evolution process. However, experimental identification of recombination spots is both time-consuming and costly. Developing an accurate and automated method for reliably and quickly identifying recombination spots is thus urgently needed.

Results

Here we proposed a novel approach by fusing features from pseudo nucleic acid composition (PseNAC), including NAC, n-tier NAC and pseudo dinucleotide composition (PseDNC). A recursive feature extraction by linear kernel support vector machine (SVM) was then used to rank the integrated feature vectors and extract optimal features. SVM was adopted for identifying recombination spots based on these optimal features. To evaluate the performance of the proposed method, jackknife cross-validation test was employed on a benchmark dataset. The overall accuracy of this approach was 84.09%, which was higher (from 0.37% to 3.79%) than those of state-of-the-art tools.

Conclusions

Comparison results suggested that linear kernel SVM is a useful vehicle for identifying recombination hot/cold spots.     

Characterization of Bacteria in the Rhizosphere Soils of Polygonum Pubescens and Their Potential in Promoting Growth and Cd,Pb, Zn Uptake by Brassica napus

Microbe-enhanced phytoremediation has been considered as a promising measure for the remediation of metal-contaminated soils. In this study, two bacterial strains JYX7 and JYX10 were isolated from rhizosphere soils of Polygonum pubescens grown in metal-polluted soil and identified as of Enterobacter sp. and Klebsiella sp. based on 16S rDNA sequences, respectively. JYX7 and JYX10 showed high Cd, Pb and Zn tolerance and increased water-soluble Cd, Pb and Zn concentrations in culture solution and metal-added soils. Two isolates produced plant growth-promoting substances such as indole acetic acid, siderophore, 1-aminocyclopropane-1-carboxylic deaminase, and solubilized inorganic phosphate. Based upon their ability in metal tolerance and solubilization, two isolates were further studied for their effects on growth and accumulation of Cd, Pb, and Zn in Brassica napus (rape) by pot experiments. Rapes inoculated with JYX7 and JYX10 had significantly higher dry weights, concentrations and uptakes of Cd, Pb, Zn in both above-ground and root tissues than those without inoculation grown in soils amended with Cd (25 mg kg^?1), Pb (200 mg kg^?1) or Zn (200 mg kg^?1). The present results demonstrated that JYX7 and JYX10 are valuable microorganism, which can improve the efficiency of phytoremediation in soils polluted by Cd, Pb, and Zn.     

Orexin-A Promotes Cell Migration in Cultured Rat Astrocytes via Ca2+-Dependent PKCα and ERK1/2 Signals

Orexin-A is an important neuropeptide involved in the regulation of feeding, arousal, energy consuming, and reward seeking in the body. The effects of orexin-A have widely studied in neurons but not in astrocytes. Here, we report that OX1R and OX2R are expressed in cultured rat astrocytes. Orexin-A stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and then induced the migration of astrocytes via its receptor OX1R but not OX2R. Orexin-A-induced ERK1/2 phosphorylation and astrocytes migration are Ca²⁺-dependent, since they could be inhibited by either chelating the extracellular Ca²⁺ or blocking the pathway of store-operated calcium entry (SOCE). Furthermore, both non-selective protein kinase C (PKC) inhibitor and PKCα selective inhibitor, but not PKCδ inhibitor, prevented the increase in ERK1/2 phosphorylation and the migration of astrocytes, indicating that the Ca²⁺-dependent PKCα acts as the downstream of the OX1R activation and mediates the orexin-A-induced increase in ERK1/2 phosphorylation and cell migration. In conclusion, these results suggest that orexin-A can stimulate ERK1/2 phosphorylation and then facilitate the migration of astrocytes via PLC-PKCα signal pathway, providing new knowledge about the functions of the OX1R in astrocytes.