Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells.

Farnesyltransferase inhibitors (FTIs) are currently under investigation for leukemia treatment. We evaluated the FTI manumycin A (manumycin) in two myeloid leukemia cell lines (U937 and HL-60). Manumycin induced nitric oxide production and apoptosis of the leukemia cells. Nitric oxide or other reactive oxygen species may induce oxidative DNA damage, and the number of apurinic sites increased after manumycin treatment, which was reversed by concurrent treatment with N-acetyl-L-cysteine. Since repair of DNA damage is important to cell survival, we hypothesized that methoxyamine, an inhibitor of base-excision repair, would enhance the antineoplastic effect of manumycin. The combination of manumycin and methoxyamine resulted in enhanced apoptosis by six criteria increased annexin V binding, release of mitochondrial cytochrome c into the cytosol, activation of caspase-9, activation of caspase-3, specific cleavage of poly-adenosyl ribose polymerase, and increase in the sub-G1 cell cycle fraction. The drug combination enhanced inhibition on the soft agar clonogenic assay and on the formazan dye cell viability assay. The effects of manumycin or manumycin plus methoxyamine on apoptosis were blocked by N-acetyl-L-cysteine, and partially by nitric oxide synthase inhibitors or scavenger of peroxide. We conclude that methoxyamine enhances manumycin-induced apoptosis in myeloid leukemia cells.     

高效液相色谱法测定盆炎灵口服液中芍药苷的含量

目的:采用高效液相色谱法测定盆炎灵口服液中芍药苷的含量.方法:用ZORBAX ODS-C18柱,以乙腈-水-异丙醇(13:86:1)为流动相;检测波长:230 nm.结果:芍药苷在1.6～8.0μg内呈良好线性关系,r=0.999 6,平均加样回收率为98.90%,RSD=1.40%(n=5).结论:方法简便,快速,可用于盆炎灵口服液的质量控制.     

类比和比较研究方法在药事管理学研究中的应用

本文对类比和比较的方法在药事管理学研究中的应用加以分析和研究,说明两种方法的区别,提出两种方法应用的范围和需要注意的问题,希望对药事管理学研究工作提供参考.     

复方大青叶合剂主要药效学研究

目的:对复方大青叶合剂进行了与临床主治功能有关的主要药效学研究.方法:解热试验、抗炎试验和抗菌试验.结果:复方大青叶合剂能明显降低因大肠杆菌细菌内毒素引起的家兔体温升高;对腹腔注射金黄色葡萄球菌、流感杆菌引起的小鼠死亡有一定的保护作用;体外抗菌试验表明对金黄色葡萄球菌、流感杆菌、肺炎双球菌、链球菌(甲、乙型)均有较好的抑菌作用.能明显抑制角叉菜胶所致的大鼠足肿胀和醋酸所致的小鼠腹腔毛细血管通透性增加.结论:复方大青叶合剂具有解热、抗菌、抗炎作用.     

甘草体外抑制呼吸道合胞病毒作用研究

目的:开发安全有效的抗呼吸道合胞病毒的新药.方法:采用细胞病变抑制实验观察甘草在Hela细胞中对呼吸道合胞病毒的抑制作用.结果:甘草半数中毒浓度(TC50)为3.43g/L;抑制呼吸道合胞病毒的半数有效浓度(EC50)为0.2535g/L,治疗指数(TI)为13.53;甘草对呼吸道合胞病毒的抑制作用存在量效反应关系;在感染后0 h、2 h、4 h、6 h、8 h,甘草均有抑制呼吸道合胞病毒的作用.结论:甘草在Hela细胞中对呼吸道合胞病毒有明显的抑制作用,其作用机制是多途径的.     

Wnt3a信号通路通过JMJD6的表观遗传修饰参与神经病理性疼痛

目的：探讨Wnt3a通过Jumonji C结构域6( Jumonji C domain 6,JMJD6)的表观遗传修饰在神经病理性疼痛 中发挥作用的机制。方法：将SD大鼠分为4组：Sham组,慢性缩窄性损伤(chronic constriction injury,CCI)组,CCI+阴性慢病毒表达载体(LV-NC)组;CCI+慢病毒过表达载体(LV-JMJD6)组。构建SD大鼠坐骨神经CCI模型和JMJD6慢病毒 表达载体。CCI术后第3天通过鞘内导管给药,按照分组分别给予生理盐水和含慢病毒的试剂(病毒滴度1×108 TU/mL) 各20 μL。监测大鼠的机械缩足阈值(paw withdrawal mechanical threshold,PWMT)和热缩足潜伏期(paw withdrawal thermal latency,PWTL),并运用蛋白质印迹法检测脊髓水平Wnt3a及NR2B蛋白的表达变化,免疫共沉淀检测JMJD6与Wnt3a之间是否存在直接相互作用。结果：与Sham组相比,CCI术后各组大鼠的PWMT明显降低和PWTL明显缩短(P<0.05)。与CCI组和CCI+LV-NC组相比,CCI+LV-JMJD6组的PWMT在术后第10和14天明显升高,PWTL在术后第14 天明显延长(P<0.05)。CCI术后第14天,CCI组及CCI+LV-NC组Wnt3a和NR2B蛋白表达水平较Sham组明显升高,鞘内注 射慢病毒载体后, CCI+LV-JMJD6组的Wnt3a和NR2B蛋白表达水平较CCI+LV-NC组降低(P<0.05)。免疫共沉淀结果显示Wnt3a与JMJD6之间无直接相互作用。结论：Wnt3a参与调节神经病理性疼痛,其作用可能与JMJD6的表观遗传修饰相关,两者可能通过间接相互作用进行调节。     

Conversional synthesis and cytotoxic evaluation of novel taxoid analogs

Four novel taxoid analogs were conversionally synthesized from the C₁₉-diterpenoid alkaloid deltaline, and their cytotoxic activities were evaluated against a small panel of cancer cell lines.     

A pilot study of nocturnal temporalis muscle activity in TMD diagnostic groups of women

Temporomandibular disorder (TMD) incidences are believed to be related to parafunctional behaviours like teeth clenching. This pilot study aimed to (i) develop an automated clench‐detection algorithm, and (ii) apply the algorithm to test for differences in nocturnal clenching in women with and without TMD. Subjects gave informed consent to participate. Adult women were categorised using Diagnostic Criteria for TMD according to presence/absence (+/?) of both TM joint disc placement (DD) and chronic pain (P) into two groups (+DD+P, ?DD?P) with 12 subjects each. Surface temporalis electromyography was recorded during oral tasks performed by subjects at two laboratory sessions. The data were used to characterise muscle activity per N of bite force (μV/N) for each subject, develop the clench‐detection algorithm and test its accuracy. Ambulatory surface temporalis electromyography was self‐recorded by each subject over three nights and analysed using the algorithm and bite force (N) versus muscle activity μV/N calibrations. Bonferroni‐adjusted homoscedastic t‐tests assessed for significant between‐group differences in clenching (P < 0·05). Sensitivity, specificity and accuracy of algorithm‐detected laboratory clenches were all ≥96%. During self‐recordings 95% of clenches had durations of <4 s and peak forces of <10 N in both groups. Mean clench durations were significantly longer (P = 0·042) in +DD+P (1·9 ± 0·8 s) than ?DD?P subjects (1·4 ± 0·4 s). Mean temporalis duty factors (%clench time/total recording time) were significantly larger (P = 0·041) in +DD+P (0·47 ± 0·34%) than ?DD?P (0·26 ±0·22%) subjects. Nocturnal temporalis muscle activities detected by a validated algorithm were longer per clench and recording time in +DD+P compared to ?DD?P women.     

颈胸交界区淋巴结肿瘤病变MDCT表现特征及其解剖、病理学基础

为了明确颈胸交界区淋巴源性肿瘤病变的MDCT影像表现特点、解剖及病理学基础,回顾性收集经病理证实的下颈部和上胸部的淋巴源性肿瘤病变69例(其中淋巴瘤41例,转移瘤28例),分析病变的MDCT表现特点及分布规律,阐明影像学表现与解剖、病理学的相关性。发现淋巴瘤41例中,病灶主要分布于颈外侧浅部21例(51.2%),颈深静脉链区27例(65.9%),锁骨上区31例(75.6%),上纵隔气管旁19例(46.3%),主动脉弓旁23例(56.1%),主肺动脉窗22例(53.7%),前上纵隔17例(41.5%),隆突下11例(26.8%),上纵隔食管旁7例(17.1%);淋巴结转移瘤28例,原发肿瘤为鼻咽癌5例、甲状腺癌7例、肺癌10例和食管癌6例,大多数循淋巴回流方向逐级转移,少部分跳跃式转移,主要分布于颈静脉链周围区23例(82.1%),锁骨上窝区21例(75%),上纵隔气管旁17例(60.7%),前上纵隔18例(64.3%),主动脉弓旁10例(35.7%),肺动脉窗11例(39.2%),上纵隔食管旁8例(28.6%)。因此,颈胸交界区域淋巴源性肿瘤病变可同时累及下颈部和上胸部,其影像学表现及优势解剖分布与其解剖、病理特点密切相关。     

中医药靶向调节p53介导的铁死亡机制研究进展

铁死亡是一种新发现的非凋亡调节性细胞死亡形式，以铁依赖性的脂质过氧化物及活性氧（ROS）累积为主要特征。p53是一种抑癌基因，可以通过介导多种关键细胞基因的转录调控，诱导细胞周期阻滞、凋亡、自噬和衰老，进而维持基因组稳定性。新近研究发现p53还可通过影响铁代谢、多不饱和脂肪酸（PUFAs）代谢、氨基酸代谢和烟酰胺腺嘌呤二核苷酸磷酸盐（NADPH）介导的多种细胞代谢过程，调控铁死亡，参与肿瘤、神经系统疾病、心血管疾病、肝病、肾病等疾病的病理进展。该文对p53介导的铁死亡在相关疾病转归中的作用机制及其影响因素进行了系统综述，同时追踪了中医药靶向调节p53介导的铁死亡防治肿瘤、脑卒中、急性心肌梗死、慢性心力衰竭、动脉粥样硬化、溃疡性结肠炎、佐剂性关节炎等疾病的研究进展，以期为相关疾病的防治提供新思路。