前列腺素E1对大鼠坐骨神经嵌压性损伤修复的影响

目的 探讨前列腺素E1(PGE1)对血管内皮生长因子(VEGF)的表达和周围神经嵌压损伤修复的影响.方法 将60只SD大鼠随机均分为生理盐水(A)组、PGE1 (B)组、正常对照(C)组.制作坐骨神经嵌压性损害的动物模型,采用免疫组化与电镜分别检测嵌压后12h、72 h及7d时大鼠背根神经节VEGF阳性神经元与嵌压后第4周大鼠背根神经节的病理变化.结果 嵌压72 h后,A、B组背根神经节VEGF阳性神经元数达到峰值,且明显大于C组(P＜0.01),B组VFGF阳性神经元数亦较A组增加(P＜0.01).嵌压后第4周,C组未见病理改变,B组电镜下病变严重程度较A组减轻.结论 PGE1可促进周围神经嵌压性损伤的修复,可能与VEGF表达的增加有关.     

RNAi沉默XIAP基因抑制MG-63细胞增殖及其分子机制

目的 探讨RNA干扰(RNAi)抑制NC-63骨肉瘤细胞X-连锁凋亡抑制蛋白(XIAP)基因的表达及其抗肿瘤的机制.方法 构建XIAP基因的短发夹RNA(shRNA)表达载体.将NC-63细胞分为空白组(A组),用空白质粒psiRNA-Con转染(B组),用psiRNA-XIAP转染(C gt).Westernblot检测XIAP蛋白的表达;MTT检测细胞的增殖;流式细胞术检测细胞周期、凋亡及半胱天冬氨酸蛋白酶9(Caspase-9)的表达;ELISA法检测细胞内血管内皮生长因子(VEGF)含量.结果 与A、B组比较,C组细胞XIAP蛋白水平、MTT值及VEGF含量均显著降低,细胞凋亡率、Caspase-9蛋白表达及G2/M期细胞所占比例增高(P＜0.05).结论 RNAi能有效抑制XIAP基因表达,抑制骨肉瘤细胞增殖活性,诱导其凋亡.其机制可能涉及Caspase家族凋亡信号转导通路的活化、DNA合成及肿瘤血管生成的抑制.     

Effect and possible mechanism of desferrioxamine on microvascular formation of ischemic myocardium in rats

目的 探讨去铁胺(DFO)对大鼠缺血心肌微血管形成的作用及可能机制.方法 48只SD大鼠随机均分为正常对照组(A组)、假手术组(B组)、结扎组(C组)和DFO 200mg/kg组(D组).术后7d,处死大鼠,免疫组化法检测微血管密度(MVD)及低氧诱导因子1α(HIF-1α)蛋白表达,RT-FCR检测HIF-1α mRNA表达.结果 与A、B组相比,C、D组MVD、HIF-1α蛋白和mRNA表达均增加(P＜0.05或P＜0.01),其中D组各指标增加更为显著(P＜0.01).结论 DFO 可以促进大鼠缺血心肌组织微血管形成;其作用机制可能与上调HIF-1α的表达有关.     

STAT3shRNA增强胰腺癌细胞Panc-1对吉西他滨化疗敏感性

目的 观察shRNA下调胰腺癌Panc-1细胞STAT3 mRNA表达后对吉西他滨化疗敏感性的影响.方法 构建靶向STAT3 mRNA的shRAN和阴性质粒,分别转染Panc-1细胞(A组和B组);另将非转染的正常Panc-1细胞分为C组和D组.A,B,C三组细胞与吉西他滨共孵育.RT-PCR和Western blot检测Panc-1中STAT3 mRNA和蛋白的表达;MTT法检测Panc-1细胞增殖能力;流式细胞术检测细胞周期.结果 A组STAT3 mRNA水平下降了61.9%,STAT3蛋白水平下降了85.7%(P＜0.01),细胞增殖能力低于B、C组(P＜0.01).与B、C组比较,A组G1期细胞比率增加(P＜0.05),细胞存活率降低(P＜0.01).结论 靶向STAT3 mRAN的shRNA可特异性降低Panc-1细胞中STAT3 mRNA及其蛋白的表达,抑制Panc-1细胞增殖,使其阻滞于G1期,从而增强吉西他滨对G1期细胞的细胞毒效应,增加吉西他滨的化疗敏感性.     

急性冠脉综合征患者Periostin、VEGF、ET-1和hs-CRP的表达及其临床意义

目的 探讨急性冠脉综合征(ACS)患者periostin、血管内皮生长因子(VEGF)、内皮素1(ET-1)及高敏C反应蛋白(hs-CRP)表达水平的变化及其临床意义.方法 ACS患者86例(ACS组)分为不稳定型心绞痛(A1组,44例)和急性心肌梗死(A2组,42例)两组;另取健康体检者40例作为正常对照(C组).血清periostin、VEGF和ET-1使用ELISA法检测,hs-CRP使用乳胶增强免疫比浊法检测.结果 血清periostin、VEGF、ET-1及hs-CRP的表达水平,ACS组明显高于C组(P＜0.05或P＜0.01),A2组明显高于A1组(P＜0.05或P＜0.01).Periostin的表达与VEGF和hs-CRP均呈正相关(P＜0.05或P＜0.01).VEGF的表达与ET-1和hs-CRP均呈正相关(P＜0.05或P＜0.01).ET-1的表达与hs-CRP呈正相关(P＜0.01).结论 ACS患者periostin、VEGF、ET-1和hs-CRP均呈高表达;联合监测这些因子有利于评估ACS病变程度.     

维A酸对HL-60细胞增殖与NF-κB、VEGF表达的影响

目的:观察维A酸对HL-60细胞增殖与NF-κB、VEGF表达的影响,以探讨维A酸治疗白血病的作用机制.方法:将不同浓度的维A酸作用于HL-60细胞72 h后,采用MTT法观察细胞生长,用ELISA法检测上清液中VEGF的含量,并用流式细胞术检测NF-κB活性表达及细胞周期.结果:HL-60细胞经维A酸作用72 h后生长显著受抑制,实验组HL-60细胞上清液中VEGF含量、NF-κB表达下降,10-6M、10-7M组与对照组相比差异显著(P＜0.05),而10-8M组与对照组比较,元显著差异(P＞0.05),其中10-6M组NF-κB表达与VEGF含量呈显著正相关(r=0.55,P＜0.01,n=6),各治疗组G1期细胞明显升高,10-6M组、10-7M组与对照组相比,差异显著(P＜0.01),而10-8M组与对照组比较,无显著差异(P＞0.05).结论:维A酸对HL-60细胞增殖有抑制作用,其作用机制可能与NF-κB活性及VEGF表达水平下调有关.     

P53和VEGF在SKOV3荷瘤裸鼠不良心理应激模型血清及移植瘤中的表达及意义

目的:探讨不良心理应激对SKOV3荷瘤裸鼠血清及移植瘤中P53、血管内皮生长因子(VEGF)蛋白水平的影响.方法:建立荷卵巢癌裸鼠不良心理应激模型,采用ELISA检测正常对照组(A)、单纯应激组(B)、单纯荷瘤组(C)和荷瘤应激组(D)各10只小鼠的血清P53和VEGF浓度,用Western blot方法分析C组和D组移植瘤中P53、VEGF蛋白表达情况;另取32例荷瘤应激和24例单纯荷瘤的裸鼠移植瘤标本,免疫组化检测P53和VEGF的蛋白表达水平.结果:A组与B组血清P53和VEGF含量比较差异无统计学意义(P＞0.05),C组的P53、VEGF含量均明显高于A组(P＜0.01),D组的血清P53、VEGF与B、C组相比差异均有统计学意义(P＜0.05或P＜0.01);D组P53、VEGF的蛋白灰度值明显高于C组(P＜0.05);免疫组化结果示P53蛋白在荷瘤应激组和单纯荷瘤组的阳性表达率分别为87.5%和62.5%,VEGF蛋白在2组的阳性表达率分别为93.8%和70.8%,差异均有统计学意义(P＜0.05).结论:不良心理应激明显促进荷瘤鼠SKOV3移植瘤生长,可能与P53和VEGF有关;P53及VEGF有望成为心理肿瘤学的分子靶标.     

槲皮素对前列腺癌PC3细胞Kras及Chk1基因表达的调节作用

目的 研究槲皮素对前列腺癌(PCa) PC3细胞Kras及Chk1基因表达水平的影响.方法 PC3细胞分为空白对照组(A组)、二甲基亚砜组(B组)和150 μmol/L槲皮素处理组(C组).采用RT-PCR方法检测槲皮素对PCa PC3细胞Kras及Chk1基因表达水平的影响.结果 C组PCa PC3细胞Kras及Chk1基因表达水平较A、B组明显下调(P＜0.05).结论 槲皮素可能通过改变Kras及Chk1等基因表达水平抑制PCa PC3细胞的生长.     

大鼠脑出血后脑水肿与VEGF表达的关系及依达拉奉的干预作用

目的 探讨脑出血后脑水肿和血管内皮生长因子(VEGF)表达的变化及依达拉奉的干预效应.方法 将180只大鼠随机均分为三组:模型组(A组)、依达拉奉治疗组(B组)和假手术组(C组).A组和B组颅内注入50 μl自体动脉血;C组注入50 μl灭菌生理盐水.B组注血前20 min腹腔注射依达拉奉溶液3 mg/kg,随后每12小时注射1次,直至处死前12 h.每组设5个观测时间点:12,24,48,72h和7d.采用干湿重法检测脑含水量,免疫组化法测定脑组织中VEGF表达.结果 A组各时间点脑含水量、VEGF阳性表达均较C组明显增加(P＜0.05);与A组相比,B组脑组织含水量降低,VEGF阳性表达增加(P＜0.05).A组脑含水量与VEGF阳性表达无直线相关性(P＞0.05).结论 VEGF在脑出血急性期主要发挥神经保护作用;依达拉奉通过上调VEGF的表达保护神经元,且对脑水肿有抑制作用.     

症状性子宫肌瘤子宫内膜中VEGF、bFGF表达的实验研究

目的 研究子宫肌瘤子宫内膜中血骨内皮生长因子(VEGF)、成纤维生长因子(bFGF)的表达,揭示症状性子宫肌瘤子宫内膜内环境的改变.方法 将子宫肌瘤65例患者根据有无月经过多的症状分为2组(A组:症状性子宫肌瘤组;B组:无症状性子宫肌瘤组),各组再根据子宫内膜病理类型进行组内分型.C组:正常子宫内膜作为对照组共12例.用免疫组化技术检测VEGF、bFGF在3组子宫内膜中表达水平.结果 VEGF及bFGF在3组子宫内膜中均有表达,VEGF、bFGF在A组子宫内膜增生期、分泌期中的表达水平高于B组及C组同型子宫内膜,差异有显著性(P＜0.05);在A组单纯性增生过长和复杂性增生过长子宫内膜中的表达水平显著低于A组及B组、C组增生期, 差异有显著性(P＜0.01).在B组与C组同型子宫内膜中的表达水平,差异无显著性 (P＞0.05).A组增生过长、增生期和分泌期子宫内膜中VEGF表达水平与bFGF表达水平呈显著正相关(r=0.829,P＜0.05;r=0.798,P＜0.01;r=0.626,P＜0.05).结论 子宫内膜内环境异常是子宫肌瘤患者产生月经过多的原因.VEGF、bFGF作为促血管生成因子发挥着重要作用.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.