姜黄素衍生物C1209抑制慢性粒细胞白血病细胞增殖与阻断Hsp90伴侣功能的关系

目的研究姜黄素衍生物C1209抑制慢性粒细胞白血病细胞增殖与阻断Hsp90伴侣功能的关系。方法采用荧光光谱法,研究不同浓度C1209与Hsp90、其N端片段（NHsp90）、M端片段（MHsp90）、C端片段（CHsp90）的相互作用,以及不同温度（293 K、303 K、310 K）下,C1209与Hsp90的相互作用;实验选取280 nm为激发波长,290510 nm的波长范围内进行荧光光谱扫描。采用孔雀绿磷钼酸铵-无机磷检测法,研究C1209对Hsp90-ATPase活性的抑制。四甲基偶氮唑蓝（MTT）法和羟基荧光素二醋酸盐琥珀酰亚胺脂（CFSE）染色法体外检测C1209对白血病细胞K562及耐伊马替尼（IM）的白血病细胞K562/G01细胞的增殖抑制作用;应用蛋白免疫印迹法检测Hsp90客户蛋白及其下游蛋白、Hsp90分子伴侣的表达。结果C1209解离常数为（14.733±0.713）μmol·L-1;C1209与Hsp90之间的主要作用力为静电作用力;C1209与Hsp90的C端片段结合能力最强。当ATP为1 mmol·L-1时,C1209作用于Hsp90的IC50值为11.4μmol·L-1。C1209呈剂量依赖性地抑制K562和K562/G01细胞的增殖,作用24 h的IC50为1.14μmol·L-1和0.56μmol·L-1;C1209影响Hsp90的分子伴侣功能,且下调K562和K562/G01细胞中Bcr-Abl、Akt、MEK、ERK、c-Raf及其相应磷酸化蛋白p-Akt、p-MEK、p-ERK等Hsp90客户蛋白及其下游蛋白的表达。结论姜黄素衍生物C1209是Hsp90抑制剂,对K562和耐IM的白血病细胞K562/G01具有明显的增殖抑制作用,可能与其抑制Hsp90的分子伴侣功能、下调Hsp90客户蛋白有关。福建省自然科学基金资助项目(No 2017J01821);;福建省卫计委青年项目(No 2015-1-72);;国家自然科学基金资助项目(No 81173096);;国家科技部“重大新药创制”科技重大专项(No 2012ZX09103-101-028);;福建省高校产学合作项目(No 2016Y4005

Study on the gene expression profile in the bone tissue in primary osteoporosis with kidney-yang deficiency syndrome

目的通过检测原发性骨质疏松症不同中医证型患者骨组织基因表达谱的差异,探讨原发性骨质疏松症肾阳虚证相关基因的信息学特征。方法随机选择原发性骨质疏松; 症患者,中医辨证分型为肾阳虚证组3例,肾阴虚证组3例,无肾虚证组3例,并选择正常骨密度人群3例设为正常对照组。用人全基因组表达谱芯片检测4组人群; 骨组织基因表达谱,筛选共同的差异表达基因,并对这些差异表达基因进行基因通路等相关功能分析。结果肾阳虚证组与正常对照组、肾阴虚证组、无肾虚证组的差; 异表达基因分别为2631条、3976条、6184条;肾阳虚证组与其他3组比较共同的差异表达基因有1037条。这些差异基因参与补体与凝血级联反应、; Hedgehog、TGF-beta、细胞周期等22条信号通路。结论原发性骨质疏松症肾阳虚证的相关基因主要与免疫调节、TGF-beta、细胞周期等; 信号通路相关。Objective To investigate the characteristics of genes expression; profiles of primary osteoporosis with kidney yang deficiency through; analyzing the gene expression difference with gene micro-array. Methods; Patient with osteoporosis were rand omly divided into kidney-yang; deficiency group (n = 3),kidney-yin deficiency group (n = 3),non-kidney; deficiency group (n = 3),according to the syndrome differentiation of; traditional Chinese medicine. Another 3 people with normal BMD were; selected as normal control. Expression profiles of the bone tissue from; 4 groups were detected to screen differentiated expression genes.; Analysis of pathway and other function among these genes was conducted.; Results The number of differentiated expression genes in kidney-yang; deficiency group were 3976,6184,and 2631,compared to kidney-yin; deficiency,non-kidney deficiency,and normal control group,respectively.; The number of common differentially expressed genes were 1037. These; genes were involved in 22 pathways,including complement and coagulation; cascades,Hedgehog signaling pathway,TGF-beta signaling pathway,and cell; cycle. Conclusion Genes related to kidney-yang deficiency syndrome in; primary osteoporosis are mainly related to complement and coagulation; cascades,Hedgehog signaling pathway,TGF-beta signaling pathway,and cell; cycle.福建省科技厅省属公益类科研院所基本科研专项; 福建省自然科学基金项

异基因造血干细胞移植患者发生口腔黏膜炎的危险因素分析

目的】探讨进行异基因造血干细胞移植（allo-HSCT）患者口腔黏膜炎（OM）的发生及其危险因素。【方法】回顾分析1996年5月至2007年3月在我院治疗的75例恶性血液病患者allo-HSCT的临床资料,分析相关因素与口腔黏膜炎发生的关系。【结果】49例（65.0%）患者发生口腔黏膜炎,其中13例（26.5%）发生Ⅲ度,14例（28.6%）发生Ⅳ度,中位发生时间移植后第5（3～8）天。单因素分析显示,患者年龄、疾病种类、移植方式与口腔黏膜炎的发生无相关性（P〉0.05）,TBI/CY（全身照射＋环磷酰胺）预处理的患者口腔黏膜炎发生率高于BU/CY（白消安＋环磷酰胺）方案（78.3%vs 59.6%,P〈0.05）,口服剂型白消安口腔黏膜炎发生率高于静脉剂型（91.2%vs 11.1%,P〈0.001）,无四氢叶酸钙（CF）解救甲氨蝶呤（MTX）口腔黏膜炎明显高于CF解救（87.0%vs 9.5%,P〈0.001）。多因素回归分析结果表明,只有含TBI预处理方案（OR=3.6,P〈0.05）、口服剂型白消安（OR=2.9,P〈0.01）、无CF解救MTX（OR=17.1,P〈0.001）是all-HSCT患者口腔黏膜炎发生的独立影响因素。【结论】使用静脉剂型BU联合CY预处理方案、CF解救MTX的患者allo-HSCT后口腔黏膜炎发生率明显减少

Synthesis and spectral characterization of {phenyl-[(pyridine-4carbonyl)amino]methyl}phosphonic acid dialkyl ester

alpha-Aminophosphonic acids and their derivates, as phosphorous analogs of amino acid, have attracted much attention because they show wide biological activities. In this paper, the title compounds, {phenyl-[(pyridine-4-carbonyl)amino]methyl}phosphonic acid dialkyl esters, were synthesized via Mannich reaction and peptide coupling reaction. Their structures were confirmed by elemental analysis, IR, H-1 NMR, C-13 NMR and MS spectra, and the antibacterial and antitumor activities of these compounds were given in this paper

SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate

共济失调是一类以运动协调性紊乱为主要特征的神经系统症状，临床表现包括步态不稳、丧失平衡、吞咽困难、眼球运动异常、肌张力受损等。厦门大学医学院神经科学研究所王鑫教授团队首次从轴突线粒体运输这一全新视角揭示了一类遗传性共济失调的发病机制，并发现抗癫痫药--丙戊酸大幅度减缓模型小鼠的疾病进程，具有较强的转化应用价值，有望为共济失调提供新的治疗手段。 该研究工作由王鑫教授指导完成，厦门大学医学院助理教授张洪峰和博士生洪育娟共同完成主要实验工作。Loss-of-function mutations in SNX14 cause autosomal recessive spinocerebellar ataxia 20, which is a form of early-onset cerebellar ataxia that lacks molecular mechanisms and mouse models. We generated Snx14-deficient mouse models and observed severe motor deficits and cell-autonomous Purkinje cell degeneration. SNX14 deficiency disrupted microtubule organization and mitochondrial transport in axons by destabilizing the microtubule-severing enzyme spastin, which is implicated in dominant hereditary spastic paraplegia with cerebellar ataxia, and compromised axonal integrity and mitochondrial function. Axonal transport disruption and mitochondrial dysfunction further led to degeneration of high-energy-demanding Purkinje cells, which resulted in the pathogenesis of cerebellar ataxia. The antiepileptic drug valproate ameliorated motor deficits and cerebellar degeneration in Snx14-deficient mice via the restoration of mitochondrial transport and function in Purkinje cells. Our study revealed an unprecedented role for SNX14-dependent axonal transport in cerebellar ataxia, demonstrated the convergence of SNX14 and spastin in mitochondrial dysfunction, and suggests valproate as a potential therapeutic agent.We thank Tim Huang for helpful discussion, Wei Mo for sharing mouse lines, Li Zhong for sharing reagents, Aidong Han, Luming Yao, Caiming Wu, Mingxia Zhu, Qingfeng Liu, Lin Zhu, Shuo Zhang, Haiping Zheng, and Changchuan Xie for technical assistance, and Cui Li for providing bioinformatics software. We also thank Novogene Co., Ltd. and PTM Biolab Co., Ltd. for technical assistance in the transcriptomic and proteomic analyses, respectively. 厦门大学医学院许华曦、赵颖俊、张云武、杜丹教授在研究过程中给予大力帮助和支持。本研究工作得到国家重点研发计划项目、国家自然科学基金、福建省自然科学基金、厦门大学校长基金的资助和支持

美国动物园考察记

1998年秋,我有幸历时2个多月,对美国6个州、2个地区共13个城市的12个动物园及3个海洋世界和水族馆进行了考察,还对美国动物园的发展历史和现今水平作了较全面的了解,并与7年前我在美国参观动物园的感受进行了比较,对美国在办园宗旨、建园思路、造园艺术、饲养环境、动物展示手段、管理方法、科普教育等方面留下了很深的新的印象