苯扎氯铵对大鼠结肠神经及平滑肌的影响

目的研究苯扎氯铵对大鼠结肠神经及平滑肌的影响。方法8~9周龄SD大鼠50只,随机分为两组。氯胺酮麻醉下开腹,实验组用0.1%苯扎氯铵处理大鼠降结肠浆膜40min,温盐水冲洗后关腹,对照组用生理盐水代替苯扎氯铵。分别于术后1、2、3、4、8周取处理段结肠行组织学检查,反转录-聚合酶链反应(RT-PCR)检测乙酰胆碱酯酶(AchE)、巢蛋白(nestin)、乙酰胆碱M3受体(Chrm3)的表达,循环水浴药理学检测平滑肌收缩功能变化。结果苯扎氯铵处理后1周,大鼠结肠神经节细胞明显减少、空泡变,3周后完全消失;结肠平滑肌对乙酰胆碱敏感性增强。结论采用0.1%苯扎氯铵可使大鼠结肠产生去神经作用,结肠平滑肌对乙酰胆碱敏感性增强。     

Differential expression of CYP1A, 2B, and 3A genes in the F344 rat following exposure to a polybrominated diphenyl ether mixture or individual components.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been detected in the environment and in mammalian tissues and fluids. Evidence indicates that PBDE mixtures induce CYPs through aryl hydrocarbon receptor (AhR)-dependent and -independent pathways. The present work has investigated the effects of individual components of a commercial PBDE mixture (DE71) on expression of CYP1A1, a biomarker for activation of the AhR (dioxin-like), and CYP2B and CYP3A, biomarkers for activation of the constitutive androstane and pregnanexreceptors (CAR and PXR), respectively, in the rat. Male F344 rats were dosed orally on three consecutive days with either DE71, PBDE components, 2,2',4,4'-tetraBDE (BDE47), 2,2',4,4',5-pentaBDE (BDE99), 2,2',4,4',5,5'-hexaBDE (BDE153), representative polybrominated dibenzofurans (PBDFs) present in DE71, or reference PCBs. Differential expression of target genes was determined in liver 24 h after the last dose. Quantitative PCR analysis indicated up-regulation of CYP1A1 by DE71; however, the response was weak compared to that for dioxin-like PCB126. Individual PBDE components of DE71 up-regulated CYP1A1 only at the highest administered dose (100 micromol/kg/day). Representative PBDFs efficiently up-regulated CYP1A1; therefore, they, along with other PBDFs and polybrominated dibenzodioxins detected in DE71 and individual PBDE components, may be responsible for most, if not all, dioxin-like properties previously observed for PBDEs. Conversely, PBDEs appear capable of up-regulating CYP2B and CYP3A in rats at doses similar to that for non-dioxin-like PCB153. These results indicate that in vivo PBDE-mediated toxicity would be better categorized by AhR-independent mechanisms, rather than the well-characterized AhR-dependent mechanism associated with exposure to dioxin-like chemicals.     

VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia.

BACKGROUND: Aplidine (APL) is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans that is under clinical phase II development. In contrast to the lack of bone marrow toxicity reported in phase I/II studies, it has been shown to induce cytotoxicity at very low concentration against lymphoblastic leukemia blast, as well as having an impact in the vascular endothelial growth factor (VEGF)/VEGF receptor 1 loop. PATIENTS AND METHODS: To confirm these findings we investigated APL-related VEGF inhibition and its cytotoxic effect on myeloid leukemic cells lines (K-562, HEL and HL60) and fresh leukemia blasts derived from 30 patients with acute myeloid leukemia (AML). The conventional active 4-demetoxi-daunorubicin (idarubicin; IDA) was included as a positive control. RESULTS: APL was found to be significantly (P<0.001) more active than IDA in obtaining 50% growth-inhibition in K-562, HEL and HL60 cell lines. Results obtained with AML blast cells were super imposible. ID(50) ranged from 0.024 to 0.610 microM for IDA (0.200+/-0.176) and from 0.001 to 0.108 microM for APL (0.020+/-0.031). Annexin V tests and cell cycle analysis performed on cell lines confirmed the stronger citotoxic capability of APL as apoptotic inducer and as a G(1) blocker. The inhibitory effects of APL on VEGF release and secretion have been confirmed by ELISA tests performed on HEL: the VEGF concentration in cell surnatant was reduced from 169 to 36 pg/ml after 24 h of exposure to a pharmacological concentration of APL. CONCLUSIONS: APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway.     

奥沙利铂联合羟基喜树碱和氟尿嘧啶及亚叶酸钙治疗晚期胃癌的临床研究

目的：观察以奥沙利铂（LOHP）、羟基喜树碱（HCPT）、氟尿嘧啶（5FU）及亚叶酸钙（LV）组成的HLOF方案和顺铂（DDP）、HCPT、5-FU及LV组成的HLPF方案治疗晚期胃癌的疗效与安全性。方法：61例患者随机分组，试验组32例给予HLOF方案化疗，L-OHP130mg／m^2，静脉滴入2h，d1；HCPT6mg／m^2，静脉滴入，d1～d3；5-FU500mg／m^2，静脉滴入．d1～d3；LV100mg／m^2，静脉滴入，d1～d3。对照组29例给予HLPF方案化疗，除用DDP替代L-OHP外余同对照组。DDP用法：30mg／m^2，静脉滴入，d1～d3。以上方案均每21～28d重复。每例至少完成2个周期化疗方可评价疗效。结果：试验组CR2例．PR17例，SD8例，PD5例，有效率为59．4％（19／32）；对照组PR12例．SD11例，PD6例，有效率为41．4％。两组总有效率差异无统计学意义，P〉0．05。不良反应HLOF组食欲下降、恶心、呕吐的发生率较对照纽低，P〈0．05；神经毒性发生率高于对照组。KPS评分HLOF组升高幅度高于对照，P〈0．05。两组疾病无进展时间（time to progress，TTP）及生存期比较，差异均无统计学意义，P〉0.05。结论：治疗晚期胃癌，两者均为有效、低毒的化疗方案。在改善生活质量和减轻消化道反应方面，HLOF优于HLPF方案。     

司帕沙星、联苯乙酸对大鼠海马神经元GABA-A和离子型谷氨酸受体的作用(英文)

目的 :观察司帕沙星单用和与联苯乙酸合用时 ,对γ 氨基丁酸 (GABA) ,NMDA ,AMPA和海人藻酸诱导电流的作用。方法 :应用全细胞式膜片钳技术在急性打散的新生大鼠海马锥体神经元上记录GABA ,NMDA ,AMPA和海人藻酸的诱导电流。结果 :司帕沙星 1mmol·L- 1对GABA诱导的电流有迅速可逆的抑制作用 ,抑制率为 (4 7.6±s2 .9) % ,而联苯乙酸 10 μmol·L- 1无抑制作用。但联苯乙酸 (10 μmol·L- 1)与司帕沙星 1mmol·L- 1合用时 ,稍稍增强抑制作用 ,司帕沙星单用或合用联苯乙酸 (10 μmol·L- 1)对GABA诱导电流的IC50 分别为 (2 38± 2 1) μmol·L- 1和 (89± 5 ) μmol·L- 1。司帕沙星、联苯乙酸或司帕沙星合用联苯乙酸对NM DA ,AMPA和海人藻酸诱导的电流无明显作用。结论 :提示司帕沙星 ,或与联苯乙酸合用时所产生的中枢神经毒性可能与抑制GABA诱导的电流有关 ,而与NMDA ,AMPA和海人藻酸诱导的电流无关。     

茶色素中两个苯骈酚酮类化合物的分离和鉴定

从茶色素中分离得到2个苯骈卓酚酮类化合物,经化学方法与光谱分析鉴定为7,8,9-三羟基苯骈卓酚酮和7,8,9-三羟基-4-羟基苯骈卓酚酮.该类化合物是首次从茶色素中分离得到的主要色素类成分.     

白木香肉桂酸-4-羟基化酶(C4H)基因的克隆及表达分析

对国产沉香的基原植物白木香Aquilaria sinensis肉桂酸-4-羟基化酶基因 C4H 编码区进行克隆,并对其进行生物信息学分析和表达分析。根据已报道的白木香伤害转录组高通量测序结果分析获得1条具有肉桂酸羟化酶酶保守结构域的 C4H 基因序列,采用RT-PCR技术克隆得到白木香 C4H 基因编码区序列,并对C4H蛋白进行生物信息学分析。另外,采用qRT-PCR方法对 C4H 基因在伤害胁迫下的表达模式进行分析。序列分析表明,所克隆的 C4H 基因编码区开放阅读框（opening reading frame,ORF）长为1 515 bp,编码514个氨基酸,GenBank登录号为KF134783。qRT-PCR实验证明 C4H 基因受不同伤害处理的诱导,分别在8,20 h达到最高表达水平。白木香 C4H 基因的编码区序列的分离克隆为进一步研究C4H蛋白在白木香中黄酮及芳香族类化合物合成途径中的功能及表达调控奠定基础。     

呼出气分析在胃癌筛查和诊断中的研究进展

近年来,胃癌的发病率和病死率都呈现上升趋势,已成为威胁健康的重大疾病之一,其诊断方法一直备受关注。由于呼出气诊断癌症具有无创、依从性高、易于操作、临床应用前景广等优点,目前已经成为癌症诊断的热门研究方向。现将胃癌呼出气诊断的相关研究进展进行归纳总结。介绍目前应用于胃癌呼出气研究的分析技术,并主要阐述呼出气挥发性有机化合物、呼出气冷凝液中与胃癌相关的肿瘤标志物,以期为呼出气早期筛查和诊断胃癌提供更多的参考依据。     

四硫化四砷对人宫颈癌细胞Hela环氧合酶表达和PGE2产生的影响

目的研究中药雄黄主要成分四硫化四砷（As4S4）对子宫颈癌细胞Hela增殖和凋亡作用的影响及其作用机制。方法以不同浓度（7．5、15、30、60mg／L）的As4S4对Hela细胞分别处理不同的时间（12、24、36、48、60h）,用四甲基偶氮唑蓝（MTY）法测定细胞增殖反应;流式细胞仪检测细胞凋亡率;Western blot检测环氧合酶-2（COX-2）蛋白的表达;用放射免疫法检测细胞PGE2释放水平。结果As4S4对Hela细胞增殖有明显的抑制作用（P〈0．01）,并呈明显的时效和量效关系,作用24h时IC50的As4S4作用浓度为30ms／L。As4S4可诱导Hela细胞凋亡,与对照组相比,差异有极显著意义（P〈0．01）,并呈浓度依赖性。As4S4可明显抑制Hela细胞COX-2的表达（P〈0．05）,随着As4S4浓度的增加,其COX-2蛋白表达水平逐渐降低。不同浓度As4S4作用24h,可明显抑制Hela细胞PGE2的分泌水平,与对照组比较差异有极显著意义（P〈0．01）。结论As4S4对Hela细胞增殖具有抑制作用,可促进细胞凋亡,其作用机制可能与抑制细胞COX-2表达和PGE2分泌水平有关。     

Shikonin from Chinese herbal medicine induces GSDME-controlled pyroptosis in tumor cellsOA

Objective:To investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin(SKN) extracted from the root of Chinese herbal medicine plant lithospermum(Lithospermum erythrorhizon Sieb. & Zucc.).Methods:We first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis.Subsequently,the HeLa cells experienced a pyroptotic process with SKN,and this was then assessed using lactate dehydrogenase(LDH) release and...