纯化眼镜蛇毒蛋白对乙酰胆碱受体通道的阻断作用

在培养的抓蟾胚胎神经和肌肉细胞上用膜片箝技术研究了从中国华南产眼镜蛇毒分离出的神经毒组分对乙酰胆碱受体（ＡＣｈ－Ｒ）通道的影响,发现它在微终板电位和单通道水平上都有明显的阻断作用。完全阻断神经肌肉接点传递的剂量约为２．０μｇ／ｍｌ,对乙酰胆碱受体通道的半阻断量约为０．２３μｇ／ｍｌ。这表明它与α－银环蛇毒有相似功效。     

天竺葵花清除自由基作用的研究

用化学发光法研究了天竺葵花粗担液对超氧阴离子自由基（Ｏ２）＾＝和羟自由基（ＯＨ）的清除作用,用分光不镀法研究了它对１,１－二苯基－２－苦肼基自由基（ＤＰＰＨ０的清除作用。结果表明,天竺葵花具有很强的清除自由基活性。其粗提物清除Ｏ２＾－分别为３．５μｇ／ｍｌ（红花）,３．０μｇ／ｍｌ（粉花）,１．６μｇ／ｍｌ（浅粉花）,与茶多酚（ＩＣ５０＝１．１μｇ／ｍｌ）相近,清除ＯＨ的ＩＣ５０分别为５．７μｇ／     

N_2和NH_4~＋培养下粪产碱菌固氮酶铁蛋白圆二色谱及热力学特性比较

Ｎ２和ＮＨ培养下粪产碱菌固氮酶铁蛋白（分别为Ａｆ２和Ａｆ＊２）的氧化态和还原态的ＣＤ谱及ＭＣＤ谱存在明显差异。还原态Ａｆ２与Ａｆ＊２在２１０ｎｍ附近的ＭＣＤ谱完全不同,但它们的氧化态ＭＣＤ谱相同。热力学测定结果表明．在２９８°Ｋ,１．０１３×１０５Ｐａ下,Ａｆ２与ＭｇＡＴＰ饱合络合时的培（△Ｈ°）变化为－２７．０ｋＪ／ｍｏｌ,自由能（△Ｇ°）变化则为－２０．８ｋＪ／ｍｏｌ．熵（△Ｓ°）变４也为－２０．６Ｊｍｏｌ－１Ｋ－１。而Ａｆ＊２与ＭｇＡＴＰ饱合络合时的烂变化为－４４．３５ｋＪ／ｍｏｌ,自由能变化为一２０．４ｋＪ／ｍｏｌ,熵变化为－７９．９Ｊｍｏｌ－１Ｋ－１。Ａｆ２与ＭｇＡＴＰ络合后再与Ｎ２培养的钼铁蛋白反应为吸热反应,而Ａｆ＊２与ＭｇＡＴＰ络合后再与ＮＨ培养的钼铁蛋白反应为放热反应。     

细菌转化黑色素的抗流感病毒作用

采用敏感的ＭＴＴ法测定了嗜麦芽假单胞菌转化黑色素的抗流感病毒作用。测定结果表明：纯化的黑色素毒性极低,对ＭＤＣＫ细胞的无毒界限为０．２ｍｇ／ｍｌ,远高于其有效的作用浓度;１０～２０μｇ／ｍｌ的黑色素能有效抑制流感病毒（血凝效价１∶３２）致细胞病变。病毒感染７２ｈ后用ＭＴＴ法测定,其宿主ＭＤＣＫ细胞保护百分率达９５％以上;此外,加黑色素后的ＭＤＣＫ细胞,抗流感病毒感染的能力优于目前抗病毒的有效药物病毒唑,前者的最佳作用浓度（２０μｇ／ｍｌ）比后者（１００μｇ／ｍｌ）低５倍。可以认为嗜麦芽假单胞菌转化黑色素具有毒性低、抗流感病毒能力强的特点     

硒对肝癌细胞凋亡作用的研究

在小鼠右腋皮下接种Ｈ２２肿瘤细胞悬液,灌服含硒液（硒酸酯多糖）有抑制皮下肿瘤块生长的作用,在人肝癌细胞株培养液中,加入一定浓度含硒液（２０μｇ／ｍｌ、５０μｇ／ｍｌ、１５０μｇ／ｍｌ）,能抑制肝癌细胞增殖,并促使细胞凋亡。与此同时,小鼠血液中谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性提高,血浆和细胞培养液中ＮＯ含量升高。探讨硒酸脂多糖引起肝癌细胞凋亡,可能与使抗氧化活性提高、阻遏自由基对癌细胞增殖的介导及促使ＮＯ释放增加有关。     

PIC-BE诱导K562/ADM细胞凋亡及逆转其MDR的研究

β榄香烯吗素（ＰＩＣ－ＢＥ）是抗癌新药β榄香烯的水溶性衍生物．采用人红白血病的多药耐药性（ＭＤＲ）细胞株Ｋ５６２／ＡＤＭ作为实验模型,观察ＰＩＣ－ＢＥ对Ｋ５６２／ＡＤＭ细胞的生长抑制和凋亡诱导作用,并进而研究其对该细胞ＭＤＲ的可能影响．结果显示：（１）Ｋ５６２／ＡＤＭ细胞对ＡＤＭ具有明显的抗性,与Ｋ５６２细胞相比,抗性倍数约为４０倍,而两者对ＰＩＣ－ＢＥ的ＩＣ５０接近,无显著差异;（２）ＰＩＣ－ＢＥ（１０．０～３０．０μｇ／ｍｌ）对Ｋ５６２／ＡＤＭ细胞具有明显的生长抑制和凋亡诱导作用,两种作用的强度在一定的范围内均具药物浓度和作用时间依赖性;（３）低毒剂量ＰＩＣ－ＢＥ（１０．０μｇ／ｍｌ）与ＡＤＭ（４．０μｇ／ｍｌ）联合应用,可显著增强ＡＤＭ对该细胞的生长抑制和凋亡诱导作用,升高细胞内ＡＤＭ的浓度,降低该细胞对ＡＤＭ的ＩＣ５０,使该细胞对ＡＤＭ的抗性有数倍逆转．上述结果提示,ＰＩＣ－ＢＥ不仅是一种有效的广谱抗肿瘤剂,而且也是一种有效的ＭＤＲ逆转剂     

含硫多肽类抗生素那西肽的菌种诱变及产量提高

那西肽（Ｎｏｓｉｈｅｐｔｉｄｅ）产生菌Ｓｔｒｅｐｔｏｍｙｃｅｓ ａｃｔｕｏｓｕｓ Ｚ１１,经ＮＴＧ处理和对Ｃｕ＾２＋,Ｍｎ＾２＋耐受选育,获得突变株Ｚ１５,其可耐受Ｃｕ＾２＋为３００μｇ／ｍｌ,耐Ｍｎ＾２＋１０００μｇ／ｍｌ,产生那西肽可达１５００μｇ／ｍｌ是Ｚ１１活力的１．６倍。     

离体大鼠不均匀牵张膈肌标本上的神经肌肉传递

在离体大鼠不均匀牵张膈肌标木（ＩＮＳＭＰ）上选择合适终板,可用同一微电极记录同一终板的小终板电住（ＭＥＰＰ）和终板电位（ＥＰＰ）。膜电位为－６２±２ｍＶ,ＭＥＰＰ频率和幅度在正常值范围,ＥＰＰ幅度高于２０ｍＶ,用直接法计算的量子含量对细胞外Ｃａ２＋浓度双对数作图呈直线,斜率为４．０６。２、５０和１００Ｈ２串刺激诱发量子释放的统计学性质为二项分布。表明ＩＮＳＭＰ上合适终板可作为电生理学上接近正常生理状态的神经肌接头模型,并提示生理状态下神经肌接头突触前诱发量子释放的机率较高（５０Ｈｚ时ｐ＝０．９）,遵循二项分布规律,递质动员较快（５０ＨＺ时为２０５０ｓ－１）,以保证正常的神经肌肉传递。     

小鼠腺病毒单克隆抗体的研制及初步应用

应用杂交瘤技术获得４株分泌抗小鼠腺病毒（ＭｕｒｉｎｅＡｄｅｎｏｖｉｒｕｓＭＡｄ）单克隆抗体细胞株,并对其特性进行分析。经鉴定,它们所分泌的抗体类型均为ＩｇＭ,腹水效价为１０－３～１０－６。相对亲和力分别为０．１μｇ／ｍｌ（Ａ９）、０．６５μｇ／ｍｌ（Ｂｌ）、１２．５μｇ／ｍｌ（Ｇ４）和２３μｇ／ｍｌ（Ｄ４）。与其他１０种鼠源性病毒均无交叉反应,表明ＭｃＡｂ具有良好的特异性。单抗标记ＦＩＴＣ后用于人用鼠源性单抗制品及各种传代细胞和原代细胞中ＭＡｄ检测,获得良好的实验结果。     

黄芪多糖和白细胞介素2对LAK细胞毒活性的调节作用

采用扶正中药黄芪的有效成分黄芪多糖（ＡＰＳ）和不同来源的白细胞介素２的伍用,探讨其对ＬＡＫ细胞毒性的调节作用,乳酸脱氢酶释放法（ＬＤＨ）测定ＬＡＫ细胞毒性的实验结果表明：ＡＰＳ自身具有增强ＬＡＫ细胞毒性的作用,有效剂量范围为１μｇ／ｍｌ￣１００μｇ／ｍｌ;ＬＡＫ细胞发挥细胞毒活性伍用一定剂量的白细胞介素２;ＡＰＳ（１０μｇ／ｍｌ）和ＩＬ－２（５００μ／ｍｌ）对ＬＡＫ细胞毒性具有非常显著的协同增强作     

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.     

Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).