组蛋白去乙酰化酶抑制剂SAHA对胰腺癌细胞Patu8988 的放射增敏作用

目的:探讨组蛋白去乙酰化酶抑制剂SAHA对胰腺癌Patu8988细胞增殖的影响和放射增敏作用。方法:用含不同浓度(0、0.5、1、2、4、6、8μmo L/L)SAHA的培养基分别培养胰腺癌Patu8988细胞12、24、36和48 h,采用MTT比色法检测SAHA作用细胞的生长抑制作用,计算IC50。设空白对照组和SAHA处理组(20%IC50 SAHA作用24 h),予6MV-X射线(0、2、4、6、8Gy)照射,克隆形成实验法检测SAHA对Patu8988细胞的放射增敏作用,单靶多击模型拟合细胞存活曲线,计算放射相关参数D0、Dq值和放射增敏比。Western blot法检测不同浓度(0、4、8、12μmo L/L)SAHA对Patu8988细胞内组蛋白H4乙酰化水平、Ku70和Bax蛋白表达的影响。结果:SAHA可抑制Patu8988细胞增殖,呈浓度和时间依赖性,48 h的IC50为5.40μmol/L。SAHA联合放疗处理Patu8988细胞的克隆形成率明显低于单独放疗处理,D0分别为1.513、2.229,Dq分别为0.783、1.321,放射增敏比(SER)为1.47。SAHA可增加Patu8988细胞内组蛋白H4乙酰化水平,抑制DNA修复蛋白Ku70表达,促进凋亡相关基因Bax表达,呈剂量依赖性,差异有统计学意义(P0.05)。结论:SAHA可以浓度和时间依赖性方式抑制胰腺癌Patu8988细胞的增殖,并具有放射增敏作用,抑制断裂DNA双链修复及促进凋亡可能是其作用机制之一。     

重组人凋亡素2 配体对放射线诱导肺腺癌A549 细胞凋亡作用的研究

目的:研究凋亡素2配体(Apo-2 ligand,Apo-2L),或称肿瘤坏死因子相关凋亡诱导配体(TNF-related apoptosis-inducing lig-and,TRAIL)在体外对人肺腺癌A549细胞系的放射增敏作用的研究。方法:MTT法检测Apo-2L单药或与放射线联合对腺癌A549细胞的抑制率,将细胞分为4组,对照组、Apo-2L组、Apo-2L+放射照射组、单纯照射组,200ng/ml、286 ng/ml的Apo-2L作用24小时后给予放射照射,照射剂量分别为:(1Gy、1.4 Gy、1.8Gy、2 Gy、3 Gy),然后进行流式细胞仪分析照射后24h各组细胞凋亡率变化。结果:MTT结果显示,腺癌A549细胞的抑制率与Apo-2L的浓度成正相关,凋亡素2配体作用24h后IC50为286ng/ml.流式细胞仪分析显示286ng/ml的Apo-2L处理24h后,细胞凋亡率从(6.68)%上升至(50)%,照射后24h Apo-2L+照射组凋亡率明显升高,为72.790%,对照组0.1185%,Apo-2L组50%,单纯照射组51.5067%。结论:Apo-2L在体外对腺癌A549细胞有抑制增殖和促进凋亡作用,并且Apo-2L联合放射线可以明显提高腺癌A549细胞的凋亡率。     

海洋细菌Pseudomonas sp．抗菌代谢产物的研究

从海洋细菌Pseudomonas sp.发酵液中分离鉴定9个环二肽和2个苯环类化合物,经波谱鉴定为环(酪氨酸-脯氨酸)(1),环(酪氨酸-异亮氨酸)(2),环(苯丙氨酸-脯氨酸)(3),环(缬氨酸-脯氨酸)(4),环(异亮氨酸-脯氨酸)(5),环(亮氨酸-脯氨酸)(6),环(丙氨酸-脯氨酸)(7),环(缬氨酸-丙氨酸)(8),环(丙氨酸-亮氨酸)(9),对羟基苯甲醛(10),二-(2-乙基己基)邻苯二甲酸酯(11).其中化合物1～4对多种海洋细菌显示一定的抗菌活性.     

中药枳壳中环肽成分的研究

运用硅胶、凝胶和高效液相色谱进行分离纯化,根据理化常数和波谱数据鉴定化合物的结构。从中药枳壳中分离并鉴定了7个环肽成分:环-(亮氨酸1-异亮氨酸2-丙氨酸3-苏氨酸4-甘氨酸5-苏氨酸6-苯丙氨酸7)(1)、环-(甘氨酸1-亮氨酸2-缬氨酸3-亮氨酸4-脯氨酸5-丝氨酸6)(2)、环-(亮氨酸1-亮氨酸2-脯氨酸3-酪氨酸4-甘氨酸5-丝氨酸6-脯氨酸7)(3)、环-(甘氨酸1-甘氨酸2-亮氨酸3-亮氨酸4-亮氨酸5-脯氨酸6-脯氨酸7-苯丙氨酸8)(4)、环-(脯氨酸-丙氨酸)(5)、环-(丙氨酸-异亮氨酸)(6)、环-(丙氨酸-亮氨酸)(7)。除2和4外,其余环肽均为首次从中药枳壳中分离得到。     

大黄鱼共生菌Bacillus coagulans LL1103的代谢产物研究

[目的]研究大黄鱼共生菌Bacillus coagulans LL1103的次生代谢产物及其抑菌活性。[方法]利用色谱层析技术对B.coagulans LL1103发酵液乙酸乙酯和正丁醇提取物进行分离纯化;运用波谱技术鉴定化合物的结构;采用微量肉汤稀释法对化合物进行抗菌活性测定。[结果]从大黄鱼内生菌B.coagulans LL1103发酵液中分离并鉴定9个环二肽类化合物,分别为:(1)环(4-羟基-脯氨酸-亮氨酸)、(2)环(异亮氨酸-丙氨酸)、(3)环(脯氨酸-缬氨酸)、(4)环(脯氨酸-苯丙氨酸)、(5)环(脯氨酸-亮氨酸)、(6)环(甘氨酸-丙氨酸)、(7)环(脯氨酸-甘氨酸)、(8)环(脯氨酸-丙氨酸)和(9)环(络氨酸-甘氨酸)。活性评价显示化合物3、7和9对大肠埃希菌(Escherichia coli)具有较强抑制作用,最低抑菌浓度(minimal inhibitory concentration,MIC)分别为8.0、4.0和16.0μg/mL。[结论]从大黄鱼共生菌B.coagulans LL1103的发酵液中分离得到3个对大肠埃希菌(E.coli)具有较好抑制活性的化合物。     

新型氮杂多肽酰肼类衍生物的设计、合成和抗肿瘤活性研究

目的:新型氮杂多肽酰肼类衍生物的设计和合成及其抗肿瘤活性研究。方法:以脯氨酸甲酯盐酸盐为原料,通过与苄氧羰基丙氨酸反应,在肼中肼解,得到所需中间体,进而与富马酸单酯反应得到目标化合物;和溴乙酸叔丁酯反应,三氟乙酸中脱去叔丁氧基,再与取代胺或氨水反应得到目标化合物。用MTT法测试合成的氮杂多肽酰肼类衍生物对肿瘤细胞的抑制活性。结果:合成了10个氮杂多肽酰肼类衍生物,其中有6个化合物对肿瘤细胞表现出抑制活性。结论:初步建立了氮杂多肽酰肼类衍生物的合成方法及其对肿瘤细胞抑制活性的构效关系。     

南海半红树植物黄槿内源真菌GT20036029代谢产物研究

应用多种色谱技术从半红树药用植物黄槿内生真菌GT20036029中分离得到9个化合物,通过波谱学方法并与已知化合物数据作比较,鉴定它们分别为N-(2-羟基苯乙基)乙酰胺(1)、环(L-脯氨酸-D-异亮氨酸)(2)、环(L-亮氨酸-L-脯氨酸)(3)、环(D-亮氨酸-L-脯氨酸)(4)、环(亮氨酸-酪氨酸)(5)、环(苯丙氨酸-丝氨酸)(6)、脑苷脂B(7)、(25S)-纽替皂苷元-3-O-α-L-鼠李糖-(1→2)-β-D-葡萄糖苷(8)和(25S)-异纽替皂苷元-3-O-α-L-鼠李糖-(1→2)-β-D-葡萄糖苷(9)。化合物1为首次从海洋真菌代谢产物中分离得到。化合物8显示了较好的肿瘤细胞生长抑制活性。     

蒙药沙参四味汤抑制人肺癌H460细胞生长作用的研究

目的:探讨蒙药沙参四味汤对人肺癌NCI-H460细胞的体外增殖抑制作用。方法:实验分为空白对照组及用药组。将人肺癌NCI-H460细胞与不同浓度的沙参四味汤(5μg/mL、10μg/mL、15μg/mL、20μg/mL、25μg/mL、30μg/mL)进行联合体外培养,采用四甲基偶氮唑蓝法(MTT法)测定不同浓度的沙参四味汤对肺癌NCI-H460细胞增殖的影响。结果:沙参四味汤对人肺癌NCI-H460细胞具有潜在的体外增殖抑制作用:不同浓度的沙参四味汤均能抑制人肺癌NCI-H460细胞的生长,分别作用24 h、48h、72 h后其最高细胞抑制率(IR)分表达到60.36%、69.31%和86.87%,24 h、48 h、72 h后其半数致死量(IC50)分别为30.60μg/mL、19.36μg/mL和14.93μg/mL。结论:沙参四味汤对人肺癌H460细胞具有体外增殖抑制作用,呈现浓度依赖性。     

虫药美洲大蠊水溶性成分及其促血管生成活性

采用色谱手段从美洲大蠊中分离得到22个化合物,利用波谱解析鉴定了它们的结构,分别命名为甘油(1)、邻羟基苯甲酸(2)、苯丙氨酸(3)、色氨酸(4)、尿嘧啶(5)、腺嘌呤(6)、环(脯氨酸-苏氨酸)(7)、环(脯氨酸-丙氨酸)(8)、环(丙氨酸-缬氨酸)(9)、环(甘氨酸-异亮氨酸)(10)、环(甘氨酸-亮氨酸)(11)、腺嘌呤核苷(12)、次黄嘌呤核苷(13)、环(亮氨酸-丝氨酸)(14)、环(丝氨酸-苯丙氨酸)(15)、环(天冬酰胺-苯丙氨酸)(16)、环(酪氨酸-甘氨酸)(17)、环(酪氨酸-丙氨酸)(18)、环(酪氨酸-丝氨酸)(19)、环(酪氨酸-苏氨酸)(20)、环(酪氨酸-天冬氨酸)(21)和Cordyrrole A(22)。其中,化合物7~11、14~22为首次从美洲大蠊中分离得到,而化合物20和21为新的天然产物。此外,对化合物抗一氧化氮生成作用和促血管生成活性进行了测试。     

色胺酮卤代衍生物的合成、抗肿瘤活性及其与G-四链体DNA相互作用研究

色胺酮(Tryptanthrin,Try)是重要的天然吲哚喹唑啉类生物碱,本文首次合成了2,8-二溴色胺酮(BrTry)及8-碘色胺酮(I-Try),并研究其抗肿瘤活性;以G-四链体DNA为靶点研究其作用机制。化合物与BEL-7404、Hep G2、NCI-H460、T-24等四种肿瘤细胞株的体外抗肿瘤活性和HL-7702正常肝细胞株的毒性实验表明,Br-Try和I-Try表现出比Try的抗肿瘤活性有不同程度的增强,而对正常细胞毒性减弱的结果。Br-Try对BEL-7404、NCI-H460和T-24肿瘤细胞株表现出比Try和顺铂更强的抗肿瘤活性,IC50值在7.08~9.68μM,而I-Try只对Hep G2细胞株表现了比Try和顺铂增强的抑制活性,IC50值为15.78±0.33μM。初步的作用机制分析表明,三种化合物与G-四链体DNA有较强作用,以Br-Try最强。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.