Hypotensive but not normotensive haemorrhage increases tryptophan hydroxylase-2 mRNA in caudal midline medulla

Severe blood loss triggers shock, a precipitous hypotension and bradycardia. The integrity of (i) neurons in the vasodepressor region of the caudal midline medulla and (ii) central 5-HT neurotransmission are critical for the expression of haemorrhagic shock. This study investigated whether progressive blood loss triggers altered synthesis of 5-HT in the vasodepressor region of the caudal midline medulla by measuring changes in relative expression levels of tryptophan hydroxylase 2 (TpH 2) mRNA, the rate-limiting enzyme in the synthesis of neuronal 5-HT. Hypotensive but not normotensive haemorrhage triggered a significant increase in TpH 2 mRNA in the vasodepressor region of the caudal midline medulla, identifying an important role for 5-HT-containing caudal midline medullary neurons in haemorrhagic shock.     

Genetic variants in DNA repair genes and the risk of cutaneous malignant melanoma in melanoma-prone families with/without CDKN2A mutations

Cutaneous malignant melanoma (CMM) is an etiologically heterogeneous disease with genetic, environmental (sun exposure) and host (pigmentation/nevi) factors and their interactions contributing to risk. Genetic variants in DNA repair genes may be particularly important since their altered function in response to sun exposure-related DNA damage maybe related to risk for CMM. However, systematic evaluations of genetic variants in DNA repair genes are limited, particularly in high-risk families. We comprehensively analyzed DNA repair gene polymorphisms and CMM risk in melanoma-prone families with/without CDKN2A mutations. A total of 586 individuals (183 CMM) from 53 families (23 CDKN2A (+), 30 CDKN2A (-)) were genotyped for 2964 tagSNPs in 131 DNA repair genes. Conditional logistic regression, conditioning on families, was used to estimate trend p-values, odds ratios and 95% confidence intervals for the association between CMM and each SNP separately, adjusted for age and sex. p-Values for SNPs in the same gene were combined to yield gene specific p-values. Two genes, POLN and PRKDC, were significantly associated with melanoma after Bonferroni correction for multiple testing (p = 0.0003 and 0.00035, respectively). DCLRE1B showed suggestive association (p = 0.0006). 28 ～ 56% of genotyped SNPs in these genes had single SNP p < 0.05. The most significant SNPs in POLN and PRKDC had similar effects in CDKN2A (+) and CDKN2A (-) families. Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations.     

清热解毒中药抗肿瘤作用研究进展

恶性肿瘤常常起因于由物理、化学以及生物(病毒、细菌和寄生虫)等因素诱发的细胞癌变,严重威胁着人类的生命和健康。清热解毒中药具有抗病原微生物、抗内毒素、抗炎、提高机体免疫能力及清除热毒等功效,能够用于治疗恶性肿瘤。鉴于该类中药在治疗恶性肿瘤过程中独特的临床疗效,以及该类中药越来越受到广泛的关注和重视,对《中国药典》2010年版载录的45种清热解毒中药的抗肿瘤作用研究进展进行概述。     

系统化学生物学在中药谱效关系研究中的应用展望

中药谱效关系是当前中药研究的前沿课题,其在中药质量控制和疗效评价中起着重要作用。谱效关系研究方法中,药效评价方法及其与化学指纹图谱的联系是必须解决的关键问题之一。现行药理学评价指标多是总体宏观指标,与化学指纹图谱数学关联度不高。系统化学生物学研究对象及内容和中药谱效关系结合紧密,而系统化学生物学中的小分子化合物对生物大分子的调控作用即体现为药效,化学信息学和化学计量学的发展为精确表述它们的关系拓宽了思路。通过对中药谱效关系研究的分析,指出将系统化学生物学方法运用到中药谱效关系研究中,旨在为谱效关系研究开辟更加广阔的道路。     

Apoptosis and melanoma: molecular mechanisms

Melanoma cells can undergo self-destruction via programmed cell death, i.e. apoptosis. In these tumours, the molecular components of apoptosis include positive (apoptotic) and negative (anti-apoptotic) regulators. The former include p53, Bid, Noxa, PUMA, Bax, TNF, TRAIL, Fas/FasL, PITSLRE, interferons, and c-KIT/SCF. The latter include Bcl-2, Bcl-X(L), Mcl-1, NF-(K)B, survivin, livin, and ML-IAP. Alternatively, some molecules such as TRAF-2, c-Myc, endothelins, and integrins may have either pro- or anti-apoptotic effects. Some of these molecules are of potential therapeutic use, such as: (1) p53, which influences resistance to chemotherapy; (2) Mcl-1 and Bcl-X(L), which can override apoptosis; (3) TRAIL, which has selective fatal effects on tumour cells; (4) NF-(K)B, which when downregulated sensitizes cells to TRAIL and TNF; (5) the PITSLRE kinases, whose alteration appears to result in Fas resistance; (6) interferons, which sensitize cells to other factors; and (7) survivin and other IAPs that inhibit apoptosis. This review summarizes the state of current knowledge about the key molecular components and mechanisms of apoptosis in melanoma, discusses potential therapeutic ramifications, and provides directions for future research.     

我国中药产业国际竞争力分析

中医中药是中华民族的文化瑰宝 ,随着中国加入 WTO,国际天然药物市场的壮大及其对中药类产品的接纳 ,给我国中药产业的发展提供了有利条件 ,但也面临着多方面的挑战 ,主要介绍了美国哈佛大学迈克尔·波特教授的产业竞争力理论 ,并使用波特的钻石模型从产业国际竞争力的角度对我国中药产业的国际竞争力进行了科学的分析 ,从而为根据我国中药产业自身的实力和所处环境选择合理策略提升我国中药产业国际竞争力提供研究基础。     

国外天然药物专利政策分析及对我国中药保护的启示

中药产业承载了悠久的中医药理论与文化,而现代专利保护将对其可继续发展和国际化产生深刻影响。但我国专利制度的历史尚短,中药专利保护政策尚不完善。通过分析德国、日本和韩国天然药物专利保护政策的先进经验,提出针对我国中药专利保护现存问题他国可以借鉴的作法。具体措施包括延长发明专利保护期,细化中药专利审查原则以及加强中药专利服务等几方面,从而完善中药专种保护政策,发挥我国中药产业特色。     

中药科研与产业的问题及对策

本文探讨了中国临近加入 ＷＴＯ的中药界所面临的形势和任务,指出目前中药科研与开发存在的问题：１．产业政策;２．病证错位及疗效指标;３．中药质量;４．低水平重复;５．多方联合攻关;６．科研及产业投资,并对上述问题进行了细致分析,提出了新形势下发展中药科研与产业的５项建议。     

中药生产关键共性新技术研究进展

为中药生产技术创新与中药现代化提供参考。归纳总结国内外相关文献报道，对2000年以来的中药生产关键共性新技术在中药生产中的应用进展进行了综述。2000年以来，中药生产关键共性新技术有超临界流体萃取技术、大孔树脂吸附分离技术、机械分离技术、膜分离技术、高速离心分离技术、超声提取技术、微波技术、酶工程技术、超细粉碎技术、薄膜包衣技术、冷冻干燥、高速逆流色谱等。新技术在中药工业化生产中存在一些问题和技术难点。有待进一步完善，但随着研究的不断深入以及国家和有关部门日益重视，必将在中药制剂的制备和生产中广泛应用，为中药现代化研究注入新的活力。     

中药制剂及给药系统的物质组释放/溶出动力学原理

介绍中药物质组释放/溶出动力学相关概念、定理和原理,以及该理论的评价原理、评价方法和基本评价过程.形象化的展示有利于理解中药物质组、物质组浓度和物质组释放度等概念,更好地将该理论推广和应用到中药给药系统设计、评价中,并在药物动力学水平赋予传统剂型新的内涵.该理论将为传统中药制剂的现代化及其评价、中药给药系统的设计和评价提供新的思路和方法学依据.