药物体外干预改善盐敏感性高血压小鼠内皮祖细胞功能研究

目的 探索改善去氧皮质酮/盐（DOCA-salt）高血压小鼠内皮祖细胞（EPC）功能的药物干预手段。方法 健康的成年C57BL/6小鼠,随机分为模型组和假手术对照组,模型组制备DOCA-salt高血压小鼠模型,用尾动脉测压法测定小鼠血压,提取其EPC并分别用流式细胞仪和荧光显微镜进行鉴定,模型组小鼠EPC分别用四氢生物蝶呤（BH₄）、超氧化物歧化酶-聚乙二醇（PEG-SOD）、N(G)-硝基-L-精氨酸（L-NNA）孵育24 h,检测其功能。结果 与对照组比较,DOCA-salt高血压小鼠的收缩压明显升高（P<0.01）,其EPC的黏附功能和小管形成功能明显受损（P<0.01）,而经BH₄、PEG-SOD、L-NNA孵育24 h后,EPC的黏附功能（P<0.01)和小管形成功能（P<0.05）均显著改善。结论 BH₄、PEG-SOD、L-NNA可有效改善DOCA-salt高血压小鼠EPC受损的功能。     

黄芪甲苷对肝纤维化模型大鼠的改善作用机制研究

目的 观察黄芪甲苷对CCl4诱导的肝纤维化模型大鼠的改善作用及可能机制。方法 将SD大鼠随机分为正常组、模型组、水飞蓟宾组(30 mg·kg^–1)、黄芪甲苷组(14 mg·kg^–1)。采用50% CCl4橄榄油溶液(1.5 mL·kg^–1)腹腔注射建立肝纤维化模型,每周2次,持续8周。然后各组大鼠按照每天10 mL·kg^–1灌胃相应药物,共4周。检测大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量;计算肝脏指数;苏木素-伊红(HE)及Masson染色观察肝组织病理变化;Western blotting检测转化生长因子(TGF-β1)、上皮间质转化标志物E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)和α-平滑肌动蛋白(α-SMA)的蛋白表达水平;实时荧光定量PCR检测TGF-β1和E-cadherin的mRNA表达水平。结果 与正常组相比,模型组大鼠肝脏指数显著升高(P<0.01),血清中ALT、AST含量明显上升(P<0.01),胶原容积分数明显增加(P<0.01),肝组织内E-cadherin蛋白表达明显下降(P<0.01),α-SMA、N-cadherin蛋白表达明显升高(P<0.01),TGF-β1 mRNA及蛋白表达水平明显上升(P<0.05或P<0.01)。与模型组比较,黄芪甲苷组肝脏指数大幅下降(P<0.01),血清中ALT和AST含量明显降低(P<0.01),胶原容积分数明显下降(P<0.01),肝组织内E-cadherin蛋白表达上调(P<0.05),α-SMA、N-cadherin蛋白表达显著下调(P<0.01),TGF-β1蛋白和mRNA表达下降(P<0.01或P<0.05)。结论 黄芪甲苷对CCl4诱导肝纤维化模型大鼠具有改善作用,其机制可能与下调N-cadherin、α-SMA、TGF-β1蛋白表达,上调E-cadherin蛋白表达有关。     

红花黄色素对佐剂型关节炎大鼠的抗炎作用研究

目的 观察红花黄色素对佐剂型关节炎大鼠的抗炎作用并探讨其机制。方法 用弗氏完全佐剂建立佐剂型关节炎大鼠模型,分为正常组、模型组、红花黄色素100,50,25 mg·kg^-1组,每组10只。排水法检测大鼠足趾肿胀度,Elisa法检测炎症因子IL-1β及TNF-α的水平,western blot法检测滑膜组织中IL-1β和TNF-α蛋白的表达。结果 与模型组相比,红花黄色素各组能显著降低佐剂型关节炎大鼠的足趾肿胀度（p<0.01或P<0.05）,降低血清中IL-1β及TNF-α含量水平（p<0.01或p<0.05）,还能降低滑膜组织中IL-1β及TNF-α蛋白的表达（p<0.01或p<0.05）。结论 红花黄色素能显著缓解佐剂型关节炎大鼠的关节炎症,其机制与下调炎症因子IL-1β及TNF-α的表达有关。     

不同基原、性状藏药佐摸兴对热毒血瘀证模型大鼠的影响

目的 探讨3种不同基原和同一基原不同性状藏药佐摸兴[昌都锦鸡儿Caragana changduenais Liou f.红色心材、鬼箭锦鸡儿 Caragana jubata(Pall.) Poir.棕色和白色心材]药材对热毒血瘀证大鼠的影响。方法 90只SD大鼠随机分9组[空白组,模型组,阿司匹林阳性组,昌都锦鸡儿高、低剂量组,鬼箭锦鸡儿棕色心材高、低剂量组,鬼箭锦鸡儿白色心材高、低剂量组],采用脂多糖联合角叉菜胶溶液制备热毒血瘀证大鼠模型,检测各组热毒血瘀证模型大鼠的血液流变学、凝血四项、血常规,采用ELISA法检测花生四烯酸(arachidonic acid,AA)、白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、血栓素B2(thromboxane B2,TXB2)的含量。结果 ①血液流变学：与模型组相比,昌都锦鸡儿显著降低大鼠全血黏度、全血还原黏度、红细胞刚性指数、红细胞变形指数、全血相对指数(P<0.01),升高血浆黏度(P<0.01);鬼箭锦鸡儿棕色心材能显著降低红细胞刚性指数(P<0.05或P<0.01),升高血浆黏度(P<0.01);鬼箭锦鸡儿白色心材能显著降低全血高切黏度、全血高切还原黏度、红细胞刚性指数、红细胞变形指数、全血高切相对指数(P<0.01)。②凝血四项：与模型组相比,昌都锦鸡儿低剂量组凝血酶时间显著降低(P<0.01),鬼箭锦鸡儿棕色高剂量组活化部分凝血活酶时间、凝血酶时间显著降低(P<0.01或P<0.05);鬼箭白色低剂量组凝血酶原时间、活化部分凝血活酶时间显著降低(P<0.01或P<0.05)。③血常规：与模型组相比,鬼箭锦鸡儿棕色低剂量组和鬼箭白色低剂量组单核细胞百分比下降(P<0.05或P<0.01);昌都锦鸡儿低剂量组大血小板数目显著增加(P<0.05);昌都锦鸡儿高剂量组大鼠血小板数目、血小板压积、大血小板数目显著增加(P<0.05或P<0.01),趋于正常大鼠。④炎症因子：与模型组相比,昌都锦鸡儿组TNF-α、IL-6、TXB2显著升高(P<0.01)。鬼箭锦鸡儿棕色心材组IL-6、TXB2显著升高(P<0.01或P<0.05)。鬼箭锦鸡儿白色心材低剂量组TXB2显著升高(P<0.01);鬼箭锦鸡儿白色心材高剂量组IL-1β、IL-6、TXB2显著升高(P<0.01),AA显著降低(P<0.05)。结论 不同基原、不同性状的佐摸兴药材对热毒血瘀证大鼠有不同程度的活血化瘀作用,对血液流变学、凝血因子、血常规、炎症介质均有不同程度的影响,且剂量不同影响程度和作用趋势不同。活血化瘀作用总体表现为昌都锦鸡儿>鬼箭锦鸡儿白色心材>鬼箭锦鸡儿棕色心材。其活血化瘀作用可能是多种途径和机制综合作用的结果。     

沉默CDK7通过下调YAP表达诱导子宫内膜癌细胞凋亡

目的 研究沉默细胞周期蛋白依赖性激酶7（CDK7）诱导Yes相关蛋白（YAP）表达下调对子宫内膜癌HEC-1-A细胞凋亡的影响。方法 利用siRNA干扰技术沉默HEC-1-A细胞中CDK7的表达，采用qPCR和Western blotting检测siRNA干扰后CDK7的表达水平，CCK-8实验检测沉默CDK7对HEC-1-A细胞活力的影响，流式细胞术检测沉默CDK7对HEC-1-A细胞凋亡的影响，Western blotting检测沉默CDK7对YAP和磷酸化YAP蛋白及其下游蛋白Cyr16、CTGF表达的影响，凋亡实验检测共转染si-CDK7和pcDNA3.1-YAP对细胞凋亡的影响。结果 转染si-CDK7后，HEC-1-A细胞中CDK7 mRNA和蛋白表达水平均显著下降（P<0.01），细胞活性显著降低（P<0.01），细胞凋亡率显著升高（P<0.01），YAP和磷酸化YAP蛋白及其下游蛋白Cyr16、CTGF表达水平明显下降（P<0.01）；共转染pcDNA3.1-YAP可逆转沉默CDK7导致的细胞凋亡（P<0.01）。结论 沉默CDK7可诱导YAP蛋白表达下调，促进子宫内膜癌HEC-1-A细胞凋亡。     

黄芪多糖对X射线辐射所致BMSCs全基因组低甲基化的防护作用

目的 研究黄芪多糖(Astragalus polysaccharide,APS)对多次X线电离辐射(ionizing radiation,IR)所致骨髓间充质干细胞(bone marrow stem cells,BMSCs)全基因组甲基化水平的影响。方法 采用APS作用于5次每次2 Gy X射线辐射的BMSCs,将BMSCs分为对照组、APS组、IR组和APS+IR组。采用胞质分裂阻断法测定微核形成率;细胞染色体核型分析检测细胞核损伤;EPIGENTEK试剂盒检测各组BMSCs全基因组甲基化程度;Westernblotting检测各组BMSCs甲基转移酶DNMT3a、DNMT3b,甲基化CpG结合蛋白2(MeCP2)、甲基化CpG结合域蛋白2(MBD2)和各组BMSCs癌基因c-Myc、H-ras,抑癌基因P53、P16的蛋白表达水平。结果 与对照组比较,IR组微核数目和染色体畸变明显增加(P<0.01),BMSCs全基因组甲基化程度明显降低(P<0.01);与IR组比较,APS+IR组微核数目和染色体畸变减少(P<0.05),BMSCs全基因组甲基化程度升高(P<0.01)。在蛋白表达上,与对照组比较,IR组DNMT3a和MeCP2均明显降低(P<0.01),c-Myc、H-ras的表达明显升高,P53、P16的表达显著降低(P<0.01);与IR组比较,APS+IR组DNMT3a和MeCP2明显升高(P<0.01或P<0.05),c-Myc、H-ras的表达降低(P<0.01),P53、P16的表达显著升高(P<0.01)。结论 黄芪多糖能够防治多次X线辐射所致BMSCs全基因组甲基化水平,降低BMSCs的恶化风险。     

丁香水提物对胰腺癌细胞增殖、迁移和侵袭的影响

目的 研究丁香水提物(aqueous extract of clove，AEC)对人胰腺癌细胞Panc-1和Panc-28增殖抑制和凋亡的影响，初步明确其分子机制。方法 Panc-1、Panc-28细胞经AEC作用后，用MTT法检测细胞增殖情况；流式细胞术检测细胞凋亡情况；克隆形成检测细胞群体依赖性情况；Transwell试验检测细胞迁移和侵袭的情况；Western blotting分析cleaved-PARP、Bax、Bcl-2和E-cadherin蛋白表达情况。结果 MTT试验结果显示，与对照组相比，在给药72 h时25 μg·mL^–1 AEC就能抑制Panc-1、Panc-28细胞的增殖，抑制率分别为(16.21±3.57)%和(22.44±4.92)%(P<0.01)。流式细胞术检测结果表明，与对照组相比，200 μg·mL^–1 AEC作用Panc-1、Panc-28细胞24 h显著诱导细胞凋亡，早期凋亡率分别为(11.52±0.34)%和(30.88±0.73)%(P<0.01)；晚期凋亡率分别为(23.59±1.04)%和(13.27±0.85)%(P<0.01)。克隆形成试验结果显示，50 μg·mL^–1AEC能显著抑制Panc-1、Panc-28细胞的集落形成(P<0.01)。Transwell试验结果表明100 μg·mL^–1AEC处理Panc-1、Panc-28细胞48 h后，迁移数目分别由对照组(275±7)个减少到(165±15)个，(227±25)个减少到(124±16)个(P<0.01)，侵袭数目分别由对照组(179±19)个减少到(106±7)个，(132±7)个减少到(61±5)个(P<0.01)。Western blotting试验结果表明，100 μg·mL^–1 AEC能显著诱导Panc-1、Panc-28细胞中cleaved-PARP(P<0.01)、E-Cadherin的蛋白表达(P<0.05)，提高Bax/Bcl-2比值(P<0.01)。结论 AEC能诱导Panc-1、Panc-28细胞凋亡，并抑制其增殖、克隆形成、迁移和侵袭的能力，其作用机制可能与细胞内E-cadherin蛋白表达升高及Bax/Bcl-2比值增加有关。     

miR-876靶向Pax6抑制胃癌细胞增殖、侵袭和迁移

目的 探讨miR-876靶向Pax6对胃癌细胞增殖、侵袭和迁移的影响。方法 采用RT-qPCR检测胃癌组织与癌旁组织中miR-876和Pax6的表达水平,分析miR-876表达与胃癌患者临床指标的关系。检测胃上皮细胞GES-1以及胃癌细胞MGC-803、BGC-823、SGC-7901中miR-876的表达水平。将MGC-803细胞分为对照组、miR-876 mimic组、mimic-NC组和miR-876 mimic+pcDNA-3.1-Pax6组,采用RT-qPCR和Western blotting检测各组细胞中miR-876以及Pax6的mRNA和蛋白表达水平;MTT检测各组细胞增殖情况;Transwell检测各组细胞迁移和侵袭情况;双荧光素酶实验验证miR-876与Pax6的靶向关系。结果 与癌旁组织相比,miR-876在胃癌组织中低表达（t=13.962, P<0.05）,而Pax6 mRNA和蛋白在胃癌组织中均呈高表达（t=23.368, 13.757; P<0.05）,且两者呈负相关（r=-0.434, P<0.05）。miR-876低表达与胃癌患者TNM分期（χ²=12.000, P<0.05）和淋巴结转移（χ²=15.705, P<0.05）有关。细胞实验发现,miR-876在胃癌细胞系MGC-803、BGC-823、SGC-7901中均低表达（P<0.05）;转染miR-876 mimic后,miR-876表达水平显著升高,细胞增殖能力减弱,迁移和侵袭能力均受到抑制（P<0.05）。双荧光素酶实验结果表明：miR-876能够靶向结合Pax6。与mimic-NC组比,miR-876 mimic组Pax6 mRNA和蛋白表达水平显著下降（P<0.05）;与miR-876 mimic组比,miR-876 mimic+pcDNA-3.1-Pax6组细胞增殖、迁移和侵袭能力均显著提高（P<0.05）。结论 miR-876靶向Pax6可抑制胃癌细胞MGC-803的增殖、侵袭和迁移。     

诺帝对血管内皮生长因子诱导的人脐血源性内皮祖细胞功能的影响

探讨手性化合物诺帝(Nordy)对血管内皮生长因子(VEGF)诱导的人脐血源性内皮祖细胞(EPCs)功能的影响及其意义。应用密度梯度离心法分离新鲜人脐血的单个核细胞，接种于EGM-2培养液中培养7～10 d获得内皮祖细胞(EPCs)。分别采用MTT法、Millicell-PCF培养小室系统和Matrigel内小管形成试验检测诺帝对VEGF刺激下EPCs增殖活性、迁移能力和体外形成小管样结构能力的影响。结果表明，100 μmol·L^-1诺帝作用24 h明显抑制EPCs增殖活性(P<0.05)，诺帝(25～50 μmol·L^-1)作用48～72 h也明显抑制EPCs增殖活性(P<0.05)。诺帝(25～100 μmol·L^-1)显著抑制VEGF诱导的EPCs迁移活性和体外形成小管样结构的能力(P<0.05)。诺帝能抑制体外VEGF诱导的人脐血源性EPCs增殖、迁移和体外小管形成能力，提示其具有抗EPCs效应。     

芹菜素对顺铂化疗所致肾损伤及Nrf2/HO-1通路的影响

目的 探索芹菜素（APG）对顺铂（DDP）化疗所致肾损伤大鼠的保护作用及机制研究。方法 将60只SD大鼠随机分为空白组、模型组、氨磷汀组（阳性对照组）及APG低、中、高剂量组,每组10只。模型组、氨磷汀组及APG低、中、高剂量组大鼠均采用一次性腹腔注射DDP（7.5 mg·kg^-1）的方法建立DDP致肾损伤大鼠模型,空白组大鼠仅腹腔注射生理盐水（不造模）;然后分别腹腔注射给药（APG低、中、高剂量组分别给予10、20、40 mg·kg^-1 APG,氨磷汀组给予1 mg·kg^-1氨磷汀,空白组和模型组均给予生理盐水）,1次/d,连续给药28 d。测定各组大鼠24 h尿蛋白量和血清肌酐（Scr）、尿素氮（BUN）含量,HE染色法、TUNEL法分别行肾脏病理学检查和细胞凋亡检测,生化分析法检测MDA含量和抗氧化酶（SOD、GSH-Px）活性,ELISA法检测炎症细胞因子（TNF-α、IL-1β、IL-6）水平,Western blotting检测核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、核因子-κB（NF-κB）、激活型半胱胺酸蛋白酶-3（Cleaved Caspase-3）蛋白的表达水平。结果 与模型组比较,APG中、高剂量组和氨磷汀组大鼠24 h尿蛋白量和血清Scr、BUN含量显著降低（P<0.05）,肾脏组织病理学改变和细胞凋亡状况明显改善,凋亡指数（AI）显著降低（P<0.01）,MDA含量显著降低且SOD、GSH-Px活性显著升高（P<0.05）,TNF-α、IL-1β、IL-6水平显著降低（P<0.05）,Nrf2、HO-1表达显著上调而NF-κB、Cleaved Caspase-3表达显著下调（P<0.01）。与氨磷汀组比较,APG高剂量组大鼠血清Scr、BUN含量显著降低（P<0.05）,肾脏组织病理学改变和细胞凋亡状况明显改善、AI显著降低（P<0.01）,MDA含量显著降低且SOD活性显著升高（P<0.01）,TNF-α、IL-1β水平显著降低（P<0.05）,Nrf2、HO-1表达显著上调且Cleaved Caspase-3表达显著下调（P<0.05）。结论 APG对DDP所致肾损伤大鼠具有保护作用,其作用机制可能与激活Nrf2/HO-1通路而抑制氧化应激损伤、炎症反应和细胞凋亡有关。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.