PPAR-γ的激动剂吡咯列酮抑制肝癌细胞生长和诱导凋亡的实验研究

目的观察PPAR—γ的激动剂吡咯列酮对肝癌细胞的生长抑制作用和诱导凋亡作用。方法吡咯列酮作用于肝癌细胞株SMMC7721。MTT法检测肝癌细胞的生长抑制率：流式细胞仪检测肝癌细胞凋亡率：RT—PCR检测肝癌细胞内PPAR-γmRNA的表达。结果吡咯列酮对肝癌细胞有明显抑制作用和诱导凋亡作用：细胞凋亡率与细胞生长抑制率之间无显著相关性（r=0.639，P=0.361）;肝癌细胞SMMC7721表达PPAR-γmRNA，随吡咯列酮浓度的增加肝癌细胞内PPAR-γmRNA的表达呈下降趋势。结论PPAR—γ的激动剂吡咯列酮可抑制肝癌细胞的生长和诱导其凋亡；但是，细胞凋亡率与生长抑制率之间无显著相关性，提示尚有诱导细胞凋亡以外的途径参与吡咯列酮对肝癌细胞的生长抑制作用;吡咯列酮可下调肝癌细胞内PPAR-γmRNA的转录．具体机制有待研究。     

水溶性壳聚糖对肝癌细胞生长抑制的实验研究

目的 观察壳聚糖对肝癌细胞SMMC7721的生长抑制作用.方法 采用MTT法研究了不同浓度水溶性壳聚糖对肝癌细胞株SMMC7721的生长抑制作用.结果 水溶性壳聚糖可抑制肝癌细胞的生长,在一定范围内(50～400mg/L)呈剂量依赖关系.结论 水溶性壳聚糖对肝癌细胞的生长有抑制,并且呈剂量依赖关系.     

壳聚糖及其衍生物对肝癌细胞SMMC7721的生长抑制作用

目的观察壳聚糖及其衍生物对肝癌细胞SMMC7721的生长抑制作用。方法采用四甲基偶氮唑盐(MTT)法研究了不同浓度水溶性壳聚糖、磺化壳聚糖、羧甲基壳聚糖和壳寡糖对肝癌细胞株SMMC7721的生长抑制作用。结果在4种不同壳聚糖及其衍生物中,水溶性壳聚糖和磺化壳聚糖可显著抑制肝癌细胞的生长,并在一定范围内(50~400 mg/L)呈剂量依赖关系,其中以磺化壳聚糖最为显著,羧甲基壳聚糖和壳寡糖对肝癌细胞无生长抑制作用。结论壳聚糖及其衍生物可抑制肝癌细胞的生长,并且呈剂量依赖关系。     

吡格列酮与曲格列酮影响肝癌细胞株SMMC-7721生长侵袭的实验研究

目的:探讨曲格列酮、吡格列酮对于肝癌细胞株SMMC-7721的生长、侵袭的影响.方法:采用四唑氮蓝还原法(MTT法)研究曲格列酮、吡格列酮对于肝癌细胞株的生长影响;细胞侵袭试验研究不同浓度的吡格列酮、曲格列酮对肝癌细胞株侵袭能力的影响.结果:MTT法及细胞侵袭试验可以发现不同浓度的曲格列酮、吡格列酮对肝癌细胞株生物学作用有影响.结论:曲格列酮、吡格列酮对于肝癌细胞株SMMC-7721生长、侵袭有明显的抑制作用.     

Cyclin L2在化疗诱导肝癌细胞凋亡中的作用

目的探讨cyclin L2基因在化疗药物顺铂（DDP）、5-氟尿嘧啶（5-FU）和多西紫杉醇（Doc）诱导的肝癌细胞凋亡中的作用。方法用肝癌SMMC7721细胞株进行培养传代，MTT试验检测DDP、5-FU和Doe不同药物浓度对肝癌细胞生长的抑制作用，以及cyclin L2转染及反义转染后对该细胞生长抑制作用的影响。用流式细胞术定量检测细胞凋亡。结果不同浓度DDP、5-FU和Doc对肝癌细胞生长均有明显的浓度依赖性抑制作用。细胞凋亡率和cyclinL2基因表达率成正相关。在5-FU和DDP作用下，cyclin L2转染组凋亡率均高于对照组（P〈0．01），反义转染组细胞凋亡率低于对照组（P〉0．05）。结论Cyclin L2基因在化疗药物诱导肝癌细胞凋亡中起重要作用。     

极大螺旋藻多糖对5种人肿瘤细胞株生长的影响

目的：观察极大螺旋藻多糖对人回盲肠癌HCT-8、神经胶质瘤U251、宫颈癌HeLa、肝癌SMMC7721、肺癌A549细胞株生长的影响。方法：体外培养条件下用不同浓度的极大螺旋藻胞内、胞外多糖处理这5种癌细胞，同时处理人正常胚肝LO-2细胞，并用SRB检测法测定。结果：极大螺旋藻胞内、胞外多糖对离体培养的宫颈癌HeLa、肝癌SMMC772l、肺癌A549等肿瘤细胞均有明显的生长抑制作用，并存在浓度剂量效应，高浓度抑制作用强；而对离体培养的人正常胚肝LO-2细胞的生长影响较弱。结论：极大螺旋藻多糖能选择性地识别并杀伤癌细胞，值得进一步研究。     

过氧化物酶体增生物激活受体γ激动剂致水肿机制及预防的研究进展

过氧化物酶体增生物激活受体γ（peroxisome proliferator-activated receptor gamma,PPAR-γ）激动剂主要包括噻唑烷二酮类（thiazolidinediones,TZDs）和非噻唑烷二酮类新型PPAR-γ激动剂。噻唑烷二酮类药物常用的有曲格列酮、吡咯列酮及罗格列酮。PPAR-γ激动剂的常见不良反应之一为水肿,并可加重或引致充血性心力衰竭。水肿发生率为3%～28.9%;PPAR-γ激动剂和其他口服降血糖药或胰岛素合用可增加水肿发生率。PPAR-γ引起水肿的机制涉及水钠潴留、血管扩张以及血管通透性增加等因素,特别是分布于远端肾小管和集合管的水、钠转运蛋白调节异常对水钠潴留的发生起重要作用。PPAR-γ激动剂引起的水肿一般较轻,停药后可消退。糖尿病合并中、重度充血性心力衰竭患者[NYHA（New York Heart Association）Ⅲ或Ⅳ级]避免用PPAR-γ激动剂,合并轻度充血性心力衰竭患者（NYHAI至Ⅱ级）应慎用,尽可能用最小剂量,必需时,剂量应逐渐增加,可联合应用利尿剂,并应严密监测患者体重和水肿的发生情况。预防治疗水肿的方法包括应用新的选择性PPAR-γ调节剂、蛋白激酶C-β或上皮细胞钠通道的特异性抑制剂及PPAR-γ拮抗剂。     

香参软胶囊对小鼠肝癌的抑制作用研究

目的：研究香参软胶囊对小鼠H22移植性肝癌腹水及其对SMMC7721荷瘤裸鼠的抗肿瘤作用。方法：昆明种小鼠腹腔注射H22肝癌细胞,建立肝癌腹水模型,观察香参软胶囊高（720mg·kg-1）、中（360mg·kg-1）、低（180mg·kg-1）剂量组灌胃给药对H22移植性肝癌腹水小鼠体征及生命延长率的影响;裸鼠右腋窝皮下接种SMMC7721细胞悬液,待察瘤块成形后给药。观察香参软胶囊高（720mg·kg-1）、中（360mg·kg-1）、低（180mg·kg-1）剂量组灌胃给药对SMMC7721荷瘤裸鼠肿瘤生长及其瘤重的影响。结果：与H22移植性小鼠肝癌腹水模型组比较,香参软胶囊高剂量组显著抑制腹围增长（P<0.01）,延长小鼠生存时间（P<0.01）;香参软胶囊中剂量组显著延长小鼠生存时间（P<0.05）。与SMMC7221荷瘤裸鼠比较,香参软胶囊各剂量组平均瘤重及肿瘤体积均小于模型组;香参软胶囊高剂量组能极显著抑制SMMC7721荷瘤裸鼠肿瘤生长,同时高剂量组对肿瘤生长的抑制作用略优于平消胶囊组。结论：香参软胶囊显著H22肝癌小鼠腹水生长,延长小鼠存活时间;香参软胶囊对裸鼠SMMC7721移植性瘤具有明显抑制作用。结果表明香参软胶囊具有较明显的抗肝癌作用。     

PPARγ激动剂吡格列酮抑制胶质瘤细胞生长、凋亡的实验研究

目的探讨过氧化物酶体增长因子活化受体了激动剂（PPARγ）吡格列酮抑制胶质瘤细胞生长的机制。方法应用细胞增殖力测定、AO／EB荧光染色、流式细胞仪检测吡格列酮抑制胶质瘤细胞生长的情况。结果吡格列酮对胶质瘤细胞株U-251的生长有抑制作用,并呈时间与剂量依赖关系（P〈0．05）;可诱导胶质瘤细胞的凋亡,呈时间依赖关系（P〈0．05）,并出现细胞凋亡征象。结论PPARγ激动剂吡格列酮对胶质瘤细胞U-251具有生长抑制作用。其可诱导胶质瘤细胞凋亡可能是细胞生长抑制的机制之一。     

黄曲霉毒素B_1对肝癌细胞株SMMC-7721的作用研究

目的通过用黄曲霉毒素B1（AFB1）处理人肝癌细胞株SMMC-7721研究AFB1对SMMC-7721细胞生长的影响。方法①首先应用96孔板培养细胞,选择适宜的细胞接种密度进行实验。②应用不同浓度的黄曲霉毒素B120g/ml、10g/ml、5g/ml、2g/ml、1.0g/ml、0.1g/ml、0.01g/ml处理人肝癌细胞株SMMC-7721,MTT法绘制细胞生长曲线,观察黄曲霉毒素B1对肝癌细胞株SMMC-7721生长的影响。结果不同浓度的AFB1对肝癌细胞株SMMC-7721的影响不同,AFB120.0g/ml、AFB110.0g/ml、AFB15.0g/ml表现为细胞毒性,呈浓度依赖性;AFB11.0g/ml、AFB10.1g/ml、AFB10.01g/ml对肝癌细胞株SMMC-7721的增殖活性具有促进作用,以AFB11.0ug/ml浓度显著,AFB10.1 g/ml、AFB10.01g/ml作用渐减弱。结论黄曲霉毒素B11.0g/ml具有增强人肝癌细胞株SMMC-7721增殖活性的作用。     

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.     

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.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.