湖北金粟兰中倍半萜二聚体化合物（+）-chlorahupetenes B对脂多糖诱导的RAW264.7细胞的抗炎作用

目的 评价湖北金粟兰中倍半萜二聚体化合物（+）-chlorahupetenes B[（+）-CHB]对脂多糖（LPS）诱导的小鼠巨噬细胞（RAW264.7）炎症反应的影响及作用机制。方法 RAW264.7细胞分为对照组（给予等体积DMSO）、模型组（给予等体积DMSO）、地塞米松磷酸钠注射液（Dex,阳性对照,1 μmol·L^-1）组和（+）-CHB低、中、高浓度（5、10、20 μmol·L^-1）组。各组分别加入相应药物孵育细胞1 h,除对照组外,其余组加入LPS （1 μg·mL^-1）诱导24 h造成炎症应答模型。细胞增殖检测法用于评估细胞活力;Griess反应检测一氧化氮（NO）浓度;酶联免疫分析检测炎症细胞因子肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6的生成;实时荧光定量PCR （qRT-PCR）检测IL-1β、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、环氧合酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）、IL-6和TNF-α mRNA表达;Western blotting检测Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核因子κB （NF-κB） p65、p-NF-κB p65、NLRP3、嘌呤能受体（P2X7）蛋白表达水平。结果 与模型组比较,（+）-CHB减少了梭形细胞数量,使大部分细胞恢复正常形态;显著抑制NO、TNF-α、IL-6、IL-1β生成（P<0.01）,显著降低COX-2、iNOS、IL-6、TNF-α、NLRP3、IL-1β mRNA水平（P<0.05、0.01）;显著降低TLR4、MyD88、NF-κB p65、p-NF-κBp65、NLRP3、P2X7蛋白表达水平（P<0.05、0.01）。结论 （+）-CHB通过抑制TLR4/MyD88/NF-κB信号通路和P2X7/NLRP3/IL-1β炎症小体轴激活缓解LPS诱导的巨噬细胞炎症反应。     

姜黄素抑制HMGB1-NF-κB信号通路减轻脂多糖诱导新生大鼠急性肺损伤实验研究

目的 分析姜黄素抑制高迁移率族蛋白B1（HMGB1）-核转录因子κB（NF-κB）信号通路减轻脂多糖（LPS）诱导新生大鼠急性肺损伤（ALI）的作用。方法 将60只新生SD雄性大鼠随机分为对照组、模型组、地塞米松（阳性药,2 mg·kg^-1）组和姜黄素低、中、高剂量（1.5、3.0、6.0 mg·kg^-1）组,每组10只。除对照组外,所有大鼠采用腹膜内注射LPS （3 mg·kg^-1）建立ALI模型。注射LPS约6 h后开始ip给药,每天1次,连续7 d,模型组和对照组大鼠ip等体积的0.1% DMSO。通过血氧分压（PaO₂）和肺干湿质量比（W/D）评估新生大鼠肺水肿情况;HE染色检测各组大鼠肺组织损伤;ELISA法检测新生大鼠支气管肺泡灌洗液（BALF）氧化应激指标超氧化物歧化酶（SOD）、髓过氧化物酶（MPO）、丙二醛（MDA）和谷胱甘肽（GSH）水平,BALF中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和HMGB1水平;Western blotting法检测大鼠肺组织胞核NF-κB、胞浆NF-κB和磷酸化核因子κB抑制因子α（p-IκBα）蛋白表达。结果 与对照组相比,模型组新生大鼠肺泡腔有渗出、肺组织结构紊乱、细胞核固缩深染、伴随大量的炎性细胞浸润,病理评分显著升高（P<0.01）; PaO₂、BALF中SOD和GSH水平显著降低（P<0.01）;肺W/D,BALF中MPO和MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著升高（P<0.01）。与模型组相比,姜黄素高、中剂量组和地塞米松组大鼠肺组织病理损伤减轻,肺泡腔渗出、炎性细胞浸润明显减少,病理评分显著降低（P<0.05、0.01）; PaO₂、BALF中SOD和GSH水平显著升高（P<0.05、0.01）;肺W/D,BALF中MPO、MDA水平,BALF中IL-6、TNF-α和HMGB1水平,NF-κB胞核/胞浆比例和胞浆p-IκBα蛋白表达水平显著降低（P<0.05、0.01）。结论 姜黄素可以通过抑制HMGB1-NF-κB信号通路减轻LPS诱导的新生大鼠ALI。     

对羟基苯甲酸通过抑制NF-κB/caspase-1信号通路抗类风湿性关节炎的研究

目的 探讨天然酚酸类化合物对羟基苯甲酸（p-hydroxybenzoic acid，HA）对完全弗氏佐剂（complete Freund’s adjuvant，CFA）诱导的佐剂性关节炎（adjuvant arthritis，AA）模型的治疗作用，并对HA的作用机制进行初步分析。方法 除正常组外，向大鼠足跖皮内注射CFA 0.1 mL诱导AA大鼠模型。将AA模型大鼠随机分为模型组，HA低、中、高剂量组（2.5，5，10 mg·kg^-1）和阳性药物组（吲哚美辛，5 mg·kg^-1），灌胃给予药物进行治疗干预，记录每组大鼠足肿胀体积、足肿胀厚度并进行关节肿胀评分；通过ELISA和qPCR检测不同剂量HA对炎症因子（TNF-α、IL-1β、IL-6）表达的影响；采用X-射线和HE染色观察足爪组织形态学和病理学变化；Western blotting检测caspase-1和NF-κB的表达。结果 HA能减轻AA大鼠关节肿胀（P<0.05）；从蛋白质和mRNA水平显著抑制炎症因子（TNF-α、IL-1β、IL-6）的产生（P<0.05），并显著降低caspase-1和NF-κB蛋白表达水平；X-射线显示HA能减轻大鼠踝关节损伤，HE染色结果显示HA能显著抑制炎症细胞的浸润和软骨表层破坏等情况（P<0.05），且这些结果均呈剂量依赖性。结论 HA可能通过抑制NF-κB/caspase-1信号通路缓解关节炎症状。     

基于TGF-β/Smad与MAPK/NF-κB信号通路探讨龟鹿二仙胶对去势大鼠骨质疏松的保护作用

目的 评价龟鹿二仙胶对去势大鼠骨质疏松的保护作用并探讨其机制。方法 120只大鼠，随机分为正常组，模型组，龟鹿二仙胶低、中、高剂量组和阿法骨化醇组，共6组，除正常组外均去势造模。龟鹿二仙胶按低、中、高剂量（0.5，1.5，2.5 g·kg^-1·d^-1），阿法骨化醇按0.1 μg·kg^-1·d^-1分别灌胃干预，正常组和模型组分别给予等量生理盐水。采用HE染色检测大鼠股骨病理改变，采用试剂盒检测股骨钙（calcium，Ca）、磷（phosphorus，P）、羟脯氨酸（hydroxyproline，Hyp）、碱性磷酸酶（alkaline phosphatase，ALP）和抗酒石酸酸性磷酸酶（tartrate-resistant acid phosphatase，TRAP），同时采用蛋白质印迹法检测去势大鼠股骨TGF-β、p-Smad-3蛋白的表达以及p-JNK、p-ERK、p-P38、p-NF-κB P65蛋白的表达。结果 与正常组比较，模型组大鼠股骨Ca、P、Hyp、ALP水平显著下降（P<0.01），TRAP水平显著升高（P<0.01），骨小梁结构排列紊乱、形态变薄且有断裂迹象，TGF-β、p-Smad-3蛋白表达水平下调以及p-JNK、p-ERK、p-P38与p-NF-κB P65蛋白表达水平上调（P<0.01）。与模型组比较，龟鹿二仙胶显著增加大鼠股骨Ca、P、Hyp、ALP水平（P<0.01），降低股骨中TRAP水平（P<0.01），改善股骨病理改变，同时龟鹿二仙胶显著诱导TGF-β、p-Smad-3蛋白表达并显著降低p-JNK、p-ERK、p-P38与p-NF-κB P65蛋白表达（P<0.01）。结论 龟鹿二仙胶能显著改善去势大鼠的骨质疏松，其机制与激活TGF-β/Smad信号通路和抑制MAPK/NF-κB信号通路有关。     

马鞭草苷对口腔扁平苔藓免疫反应的抑制作用及机制

目的 探讨马鞭草苷对口腔扁平苔藓（OLP）免疫反应的抑制作用及机制。方法 用脂多糖（LPS）体外刺激角质形成细胞系HaCaT细胞构建OLP炎症模型,CCK-8法检测细胞活力;实时荧光定量聚合酶链式反应（PCR）法检测细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的基因表达变化;蛋白质印迹法检测细胞中核因子-κB p65（NF-κB p65）和p-NF-κB p65蛋白的表达变化。结果 在HaCaT细胞中,LPS刺激抑制细胞活力,并诱导TNF-α、IL-1β和IL-6基因的表达上调,以及NF-κB p65和p-NF-κB p65蛋白的表达上调;20 mg/L马鞭草苷作用24 h可减轻LPS诱导的HaCaT细胞损伤、抑制炎症因子的表达和NF-κB p65信号通路的活化;同时,经G蛋白偶联受体18（GRP18）抑制剂O1918预处理后,马鞭草苷的保护作用显著减弱。结论 马鞭草苷可以通过激活GPR18受体抑制NF-κB信号通路的活化,进而降低炎症因子的表达和减轻OLP口腔黏膜炎症反应。     

基于NF-κB/NLRP3/Caspase-1信号轴探究白藜芦醇对痛风性肾病模型大鼠肾脏的保护作用机制

目的 基于NF-κB/NLRP3/Caspase-1信号轴探究白藜芦醇对痛风性肾病模型大鼠的肾脏的保护作用机制。方法 将60只SD雄性大鼠随机分为对照组、模型组、秋水仙碱（阳性对照,0.03 mg · kg^-1）组和白藜芦醇高、中、低剂量（1 000、500、250 mg·kg^-1）组,连续7 d ig给药,给药过程中,除对照组外,其余各组使用氧嗪酸钾合并尿酸钠的方法制备大鼠痛风性肾病模型。ELISA法检测大鼠血清中白细胞介素（IL）-1β、IL-18、尿酸、肌酐（SCr）、尿素氮（BUN）水平,肾脏组织匀浆中肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）、环氧合酶-2（COX-2）水平;HE、Masson染色观察肾脏组织细胞形态变化;PAS染色检测大鼠肾组织中肾小球损伤情况,TUNEL观察肾脏组织细胞DNA损伤情况;实时荧光定量PCR （qRT-PCR）、免疫组化法检测肾脏组织中核因子-κB （NF-κB）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、半胱氨酸蛋白酶-1（Caspase-1） mRNA以及蛋白的表达量,最后采用分子对接研究白藜芦醇与NF-κB、NLRP3、Caspase-1的结合情况。结果 与模型组比较,秋水仙碱组及白藜芦醇各给药组大鼠血清中IL-1β、IL-18、SCr、BUN及肾脏TNF-α、MCP-1、COX-2水平显著降低（P<0.01）,白藜芦醇高剂量组尿酸、中和高剂量组BUN显著降低（P<0.05）;白藜芦醇各剂量组不同程度降低肾组织中胶原纤维化面积、肾小球阳性率以及肾组织细胞TUNEL染色阳性率,减缓病理损伤情况,其中高剂量组作用最显著（P<0.05）;qRT-PCR、免疫组化结果表明,白藜芦醇各给药组均抑制肾脏组织细胞中NF-κB、NLRP3、Caspase-1mRNA和蛋白的表达,其中高剂量组作用最显著（P<0.05）;分子对接结果进一步表明,白藜芦醇与NF-κB、NLRP3、Caspase-1结合状态良好,即白藜芦醇对NF-κB、NLRP3、Caspase-1具有良好的靶向调控作用。结论 白藜芦醇对痛风性肾病模型大鼠的肾脏保护作用可能为抑制NF-κB信号通路,进而抑制NLRP3的激活从而阻断Caspase-1招募IL-1β、IL-18,降低其分泌,遏制肾脏细胞程序性死亡的初始阶段细胞焦亡的发生,从而逆转痛风性肾病大鼠肾组织的炎症损伤。     

槲皮素脂质体抑制小鼠肺组织炎症作用的研究

目的 制备槲皮素脂质体以提高水溶性,研究槲皮素脂质体对脂多糖（LPS）诱导的小鼠炎症性肺损伤的作用。方法 采用薄膜分散法将槲皮素包裹于脂质体中,使用粒度分析仪测定其粒径和电位,使用透射电镜观察脂质体形貌特征。将20只C57BL/6小鼠随机分为5组：对照组、模型组、空白脂质体组、槲皮素（20mg·kg^-1）组和槲皮素脂质体（以槲皮素计20mg·kg^-1）组,每组4只。对照组不做处理,其余各组ip 3mg·kg^-1LPS,2h后ip相应药物,24h后取出肺组织进行苏木素-伊红染色观察肺组织病理变化;Westernblotting法检测白细胞介素（IL）-1β蛋白表达;实时荧光定量PCR（qRTPCR）法检测IL-1β、IL-6、肿瘤坏死因子-α（TNF-α）的mRNA表达。结果 槲皮素脂质体呈圆球状,粒径135nm,多分散系数0.260,电位（-4.28±0.66）mV。与模型组比较,槲皮素脂质体20mg·kg^-1能显著改善炎症引发的肺部结构变化,减轻免疫细胞浸润肺组织导致的肺泡壁增厚和肺泡结构紊乱,而槲皮素20mg·kg^-1没有表现出治疗效果;与模型组比较,槲皮素脂质体20mg·kg^-1可显著抑制肺组织成熟IL-1β蛋白表达（P＜0.01）,显著下调IL-1β、IL-6、TNF-α的mRNA表达（P＜0.01）,而槲皮素20mg·kg^-1不具有抑制作用。结论 脂质体制剂增强了槲皮素对小鼠肺部炎症的抑制作用,减轻了LPS引起的肺组织损伤。     

商陆皂苷甲抑制TLR4/NF-κB信号通路改善大鼠动脉粥样硬化的作用研究

目的 研究商陆皂苷甲（EsA）对动脉粥样硬化（AS）大鼠的作用及机制。方法 将SD雄性大鼠随机分为对照组、模型组、辛伐他汀片（SIMT,10mg·kg^-1,阳性对照）组和EsA高、低剂量（10、2.5mg·kg^-1）组,每组6只。对照组给予普通饲料,其余各组以高脂饲料联合ip7×10⁵U·kg^-1维生素D₃（在第3天注射）制备AS模型。造模的同时ip给药,每天1次。采用全自动生化分析仪检测各组大鼠血清总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平;ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）水平;HE染色法观察胸主动脉病理变化;Western blotting法检测胸主动脉Toll样受体4（TLR4）和髓样分化因子88（MyD88）蛋白表达;免疫组化法检测胸主动脉核因子κB（NF-κB） p65阳性细胞表达。结果 与对照组比较,模型组大鼠血清中TC、TG、LDL-C、TNF-α、IL-6和IL-1β水平显著升高（P＜0.01）,HDL-C水平显著降低（P＜0.01）;胸主动脉血管内皮损伤严重,可见明显蓝色钙状斑块;胸主动脉TLR4和MyD88蛋白表达以及NF-κB p65阳性细胞表达显著升高（P＜0.01）。与模型组比较,EsA高、低剂量组大鼠血清血脂和炎性因子水平明显改善（P＜0.05、0.01）;胸主动脉血管内皮大致恢复正常,蓝色钙状斑块减少;胸主动脉TLR4和MyD88蛋白表达以及NF-κB p65阳性细胞表达显著降低（P＜0.05、0.01）。结论 EsA可能通过抑制TLR4/NF-κB信号通路对大鼠AS发挥改善作用。     

丹酚酸B镁对兔急性心梗再灌注后无复流心肌损伤的保护作用

目的 评价丹酚酸B镁（salvianolic acid B,Sal-B）对兔急性心肌梗死再灌注后心肌损伤的保护作用。方法 新西兰大白兔40只随机分成4组,即假手术组、心肌缺血再灌注（myocardial ischemia/reperfusion,MI/R）、再灌注低剂量组（Sal-B20 mg·kg^-1组）、再灌注高剂量组（Sal-B 60 mg·kg^-1组）,每组10只。假手术组只开胸不结扎,其余3组结扎左室缘支90 min,切断结扎线120 min,建立MI/R模型。各组分别于结扎左心室缘支前5 min、结扎后90 min、再灌注120 min时取血,检测肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I （cTnI）,并评估缺血范围、无复流范围及梗死区心肌范围。结果 结扎90 min后,MI/R组、Sal-B 20 mg·kg^-1组和Sal-B 60 mg·kg^-1组3组之间CK-MB、cTnI水平差异无统计学意义。再灌注120 min后,Sal-B 60 mg·kg^-1组的血清CK-MB、cTnI水平显著低于MI/R组、Sal-B 20 mg·kg^-1组,差异有统计学意义（P<0.05）。各组染色所测的冠脉结扎区心肌缺血范围基本一致。与MI/R组、Sal-B 20 mg·kg^-1组比,Sal-B 60 mg·kg^-1组可以显著减少无复流面积（P<0.05）和梗死面积（P<0.05）,MI/R组和Sal-B 20 mg·kg^-1组之间差异无统计学意义。结论 Sal-B 60 mg·kg^-1能在一定程度上减轻心肌细胞结构损伤,缩小心肌梗死面积,减轻无复流的发生。     

依普利酮对糖尿病肾病大鼠的保护机制研究

目的 探讨依普利酮对糖尿病肾病（diabetic nephropathy,DN）大鼠的保护机制。方法 DN模型大鼠随机分成模型组、依普利酮组（40 mg·kg^-1）、阳性对照组（缬沙坦,20 mg·kg^-1）,另设正常组。灌胃给药8周。全自动生化分析仪检测24 h尿蛋白、血肌酐及血糖化血红蛋白水平;HE染色行肾组织病理形态学观察;ELISA检测肾组织IL-6、TNF-α和MCP-1水平;qPCR检测TLR4、NF-κB p65 mRNA水平,Western blot法检测肾组织TLR4、NF-κB p65蛋白水平。结果 与模型组比较,依普利酮组大鼠24 h尿蛋白、血肌酐及血糖化血红蛋白水平均明显下降（P<0.05或P<0.01）;肾组织病理变化有不同程度的改善;肾组织IL-6、TNF-α和MCP-1水平均明显下降（P<0.05或P<0.01）,TLR4、NF-κB p65 mRNA水平和TLR4、NF-κB p65蛋白水平明显下降（P<0.01）。结论 依普利酮能有效地改善DN大鼠的炎症水平,机制可能与下调IL-6、TNF-α、MCP-1、TLR4、NF-κB p65水平有关。     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.