氯过氧化物酶发酵相关指标及其关联性分析

通过考察氯过氧化物酶(CPO)发酵相关参数的动力学特征,探究酶产量与参数之间的关联性。结果表明:CPO发酵过程中慢速C源麦芽糖比葡萄糖更有利于调控CPO的稳定合成,前者CPO最高比酶活(179.50 U/m L)比后者(135 U/m L)高出44.5 U/m L,而且产酶高峰期延迟1~2 d;发酵过程p H波动与C源消耗速率密切相关,且对CPO合成具有明显的指标性作用。通过生物量曲线及糖消耗曲线与产酶特征对比判断,菌株合成CPO为中期合成类型。副产物黑色素是菌体成熟时期的一种次生代谢物质,与酶的生物合成存在时间上的同步性。控制C源基质和p H对提高CPO稳定化生产具有一定成效。     

新型N-取代吡咯类化合物的体外抗肿瘤活性研究

目的:研究37个新型N-取代吡咯类化合物的体外抗肿瘤活性,并探讨这些化合物的结构-活性关系。方法:运用MTT法来测试37个化合物对5种肿瘤细胞和1种正常细胞的体外细胞增殖抑制活性。结果:化合物3f活性最高,其对MGC80-3的IC50值为61.29μM。同时成功地总结了新型N-取代吡咯化合物的构效关系:(1)对于吡咯母核的3位,取代苯环上对位氯取代和对位叔丁基取代化合物的抗肿瘤活性差不多,并且没有明显的规律性。(2)对于吡咯母核的4位,取代基团的电子云密度对抗肿瘤活性的影响也没有明显的规律。(3)对于吡咯母核的1位,当3位为对叔丁基苯基取代时,其整体活性顺序为:(苄基,溴乙基)(甲基,乙基,丙基,丁基)乙烯基;当3位为对氯苯基取代时,其整体活性顺序为:(乙烯基,苄基)(甲基,乙基,丙基,丁基)。结论:为了得到更好的抗肿瘤活性化合物,吡咯母核的1号位置上应该接入苄基等大空间位阻基团、容易形成氢键的基团或者不接入任何取代基,从而为吡咯类化合物的进一步结构修饰以开发更高活性的抗肿瘤化合物提供指导。     

肿瘤放化综合治疗中的靶向研究

放化疗综合应用是癌症治疗中的常用方法。研究表明,放化疗综合应用可以有效地控制杀伤肿瘤,但过程中对正常细胞的毒副作用严重制约着放化疗的剂量和疗效。如何在有效杀伤肿瘤细胞的同时减轻放化疗综合应用中对正常细胞的毒副作用已经成为探索更好的治疗策略的关键。随着研究的不断深入,各种相关的新药和新治疗思路层出不穷,比如针对肿瘤发生及代谢过程的靶向类新药、用于辐射增敏的新的基因靶点等都已进入研究者的视线。另外,近年来关于肿瘤细胞中药物转运蛋白的研究也为综合治疗靶点寻找提供了一定依据。本文根据当前研究现状,着重总结近年来放化疗综合治疗靶向研究在上述几方面的一些新进展。     

2型糖尿病合并下肢动脉粥样硬化的危险因素

下肢动脉粥样硬化是2型糖尿病(T2DM)患者最常见的大血管并发症之一。作为T2DM患者严重的慢并发症之一,下肢动脉粥样硬化可引起糖尿病足的发生,严重情况下可导致足坏疽。因此,阐明T2DM合并下肢动脉粥样硬化的危险因素,早期预防和治疗糖尿病合并下肢动脉粥样硬化症,不仅提高了患者的生活质量,而且减轻了家庭和社会的经济负担,具有较大的现实意义。影响T2DM患者下肢动脉粥样硬化的因素错综复杂,分为不可调控的和可调控的因素,不可调控的危险因素包括年龄、种族、遗传等,可调控的危险因素包括吸烟、高血糖、高血脂、高血压,以及近年提出的肥胖、胰岛素抵抗、高纤维蛋白血症、炎症等。本文就T2DM合并下肢动脉粥样硬化的危险因素做一综述。     

陕西省安康市居民健康相关行为及影响因素分析

目的:探讨陕西省安康市居民健康相关行为及影响因素,为以后开展安康市社区居民健康教育提供数据。方法:选择定额抽样法,对安康市的15岁以上的4500名居民的健康行为行为进行问卷调查,其中2370名医院门诊患者、2130名社区居民,问卷调查内容包含吸烟、酗酒、运动锻炼与获取卫生保健知识的主动性,采用Logistic回归、X2检验进行影响因素分析。结果:经过调查得知,12.9%吸烟者、6.9%的酗酒者、61.8%经常参加运动锻炼者、67.1%主动获取保健知识者。通过Logistic分析得知,年龄是酗酒、获取卫生知识主动性的影响因素;性别是影响吸烟、酗酒、获取卫生保健知识主动性的影响因素;文化程度是吸烟、酗酒、获取卫生保健知识主动性的影响因素;在业状况是运动锻炼、获取卫生保健知识主动性的影响因素。结论:经过本次调查分析后,陕西省安康市的居民健康相关行为主要与在业状况、性别与文化程度相关,协助城市居民养成良好的健康行为,健康教育主要目标是阻止危害健康的行为,以提高全民的健康水平。     

Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation,Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood–brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG₂₀₀₀) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration–time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 μg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 μg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG₂₀₀₀ had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.KEY WORDS: breviscapine, microdialysis, mixed PEGylation, P-glycoprotein (P-gp), solid lipid nanoparticles     

TNF-α Mediated Increase of HIF-1α Inhibits VASP Expression,Which Reduces Alveolar-Capillary Barrier Function during Acute Lung Injury (ALI)

Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-α) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0–100 ng/mL) of TNF-α, 0.1 to 8 ng/mL TNF-α exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-α group (control group). However, 10 ng/mL and 100 ng/mL TNF-α dramatically inhibited the viability of A549 cells compared with the control group (*p<0.05). Monolayer cell permeability assay results indicated that A549 cells incubated with 10 ng/mL TNF-α for 24 hours displayed significantly increased cell permeability (*p<0.05). Moreover, the inhibition of VASP expression increased the cell permeability (*p<0.05). Pretreating A549 cells with cobalt chloride (to mimic a hypoxia environment) increased protein expression level of hypoxia inducible factor-1α (HIF-1α) (*p<0.05), whereas protein expression level of VASP decreased significantly (*p<0.05). In LPS-induced ALI mice, the concentrations of TNF-α in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1α protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**p<0.001), whereas the VASP protein expression level decreased significantly (**p<0.01). Taken together, our data demonstrate that HIF-1α acts downstream of TNF-α to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier.     

鸡、鸭甲状腺激素应答基因(THRSP)的研究进展

甲状腺激素应答Spot 14(Thyroid hormone responsive spot 14, THRSP)是一个参与多种脂肪合成限速酶基因表达的转录调控因子, 在动物肝脏、乳腺和脂肪组织中高度表达。家禽中鸡和鸭THRSP基因在cDNA水平均发现THRSPα和THRSPβ两种同工型, 其中鸡THRSPα基因编码区碱基的插入/缺失影响鸡体重和腹脂性状, 与鸡的生长发育和脂肪代谢有关。文章综述了鸡THRSP基因与鸭同源基因结构特性和表达差异, 以及鸡、鸭THRSP基因多态性及其遗传效应。     

电导率作为流域水文变化指标初探

利用电导率作为主要指标, 研究了四川黑水河流域的水文特征.方差分析表明, 支流和干流上共10个样点的电导率值在采样地点间差异显著（枯水期和平水期,P＝0000）,但在时间上不具显著性差异（枯水期P＝0346,平水期P=0517）;对枯水期和平水期各样点的电导率值做配对t检验,得出两个时期的电导率值虽差异显著,但具有极其相似的动态规律（r=0973,P＝0000）,表明流域内电导率呈规律性的变化.可将电导率应用于水文时期的划分以及河流特征的标识等研究.通过计算支流电导率对邻近干流的贡献,可以推算各支流流量的贡献率.将电导率作为流域水文时空变化的特征性指标,可为深入研究河流水文变化提供更便捷的途径.