E-cadherin在尖锐湿疣及宫颈鳞癌中的表达及意义

目的探讨E-钙黏蛋白(E-cadherin)在尖锐湿疣及宫颈鳞癌(cervical squamous cell carcino-ma)组织中的表达及意义。方法对40例尖锐湿疣、30例宫颈鳞癌及30例正常皮肤组织采用免疫组化SP法检测E-钙黏蛋白的表达。结果 E-cadherin在尖锐湿疣组织中表达较正常对照组下调,差异有统计学意义(P<0.01);E-cadherin在宫颈鳞癌组织中表达较正常对照组显著下调,差异有统计学意义(P<0.01);E-cad在尖锐湿疣与宫颈鳞癌组织中的表达呈正相关(r=0.96,P<0.05)。结论 E-cadherin在尖锐湿疣的发病机制中起一定作用,并与细胞的恶性转化有关。     

食管鳞癌中TROP2与EMT的表达及相关性研究

目的探讨TROP2在食管鳞癌组织中的表达,分析其与上皮-间质转化(EMT)的关系及临床意义。方法采用免疫组织化学方法检测50例食管鳞癌患者根治术后的癌组织、配对癌旁正常组织TROP2的表达水平,检测食管鳞癌组织EMT相关标记物N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)和E-钙黏蛋白(E-cadherin)的表达,分析TROP2与临床病理资料、TROP2与EMT相关标记物的相关性。结果食管鳞癌组织中TROP2表达明显高于癌旁正常组织(P 0.001)。食管鳞癌组织中TROP2、N-cadherin、Vimentin和E-cadherin的阳性表达率分别为62.0%、54.0%、56.0%和40.0%,TROP2表达与N-cadherin及Vimentin表达呈正相关(r=0.352,r=0.468,P 0.05),与E-cadherin表达呈负相关(r=-0.454,P 0.05)。与组织学分级、淋巴结转移、浸润范围及临床分期相关(P 0.05)。结论 BMP10在食管鳞癌组织中高表达,可能参与了食管鳞癌的EMT和肿瘤进展的调控。     

E-cadherin在小肠腺癌、小肠腺瘤中的表达及其意义

目的探讨上皮性钙黏蛋白(E-cadherin)在小肠腺癌、小肠腺瘤及癌旁正常组织中的表达及其与小肠腺癌侵袭、转移的关系。方法应用免疫组化法观察42例小肠腺癌组织、16例小肠腺瘤组织及21例癌旁正常组织中E-cadherin蛋白的表达情况。结果 E-cadherin在小肠腺癌组织中的阳性表达率(38.1%)明显低于腺瘤组织(87.5%)和癌旁正常组织(90.4%)(P<0.01)。E-cadherin低表达与肿瘤分化程度、浸润深度及淋巴结转移有关(P<0.05),而与患者的性别、年龄及肿瘤大小、部位均无关(P>0.05)。结论 E-cadherin表达下调可能与小肠腺癌发生、发展有关,在小肠腺癌的恶性演进过程中具有重要意义,可作为新的生物学标志物。     

FOXQ1和E-cadherin在食管鳞状细胞癌中的表达及临床意义

目的探讨叉头框蛋白Q1(FOXQ1)和E-钙黏蛋白(E-cadherin)在食管鳞状细胞癌(ESCC)中的表达及临床意义。方法采用免疫组织化学法检测42例ESCC组织(ESCC组)及其癌旁正常食管鳞状上皮组织(正常组)中FOXQ1和E-cadherin的表达情况,分析其表达与患者临床病理特征及预后的关系。结果 ESCC组FOXQ1的阳性表达率高于正常组(64.29%vs 28.57%,χ2=5.384,P<0.05),E-cadherin的阳性表达率低于正常组(52.38%vs 90.48%,χ2=7.691,P<0.05)。FOXQ1的表达强度在不同TNM分期及不同淋巴结转移情况间的差异有统计学意义,E-cad-herin的表达强度在不同浸润深度、分化程度、TNM分期和淋巴结转移情况间的差异有统计学意义。ESCC组织中FOXQ1和E-cadherin的表达呈负相关(r=-0.412,P<0.05)。FOXQ1高表达者的5年生存率低于低表达者(18.52%vs 66.67%,χ2=9.737,P<0.05),E-cadherin高表达者的5年生存率高于低表达者(59.09%vs 10.00%,χ2=10.996,P<0.05)。COX比例风险回归模型分析结果显示,FOXQ1高表达、E-cadherin低表达、有淋巴结转移是影响ESCC患者预后的独立危险因素。结论 FOXQ1和E-cadherin在ESCC组织中的表达呈现较好的相关性,联合检测两者的表达对于ESCC患者的预后判断及指导治疗具有一定的临床价值。     

埃兹蛋白和上皮型钙黏蛋白在肾透明细胞癌的表达及意义

目的:探讨埃兹蛋白(Ezrin)和上皮型钙黏蛋白(E-cadherin)在肾透明细胞癌及癌旁正常肾组织中的表达及与肿瘤侵袭、转移的关系.方法:采用免疫组织化学Elivision方法检测45例肾透明细胞癌组织及相应癌旁正常肾组织中Ezrin和E-cadherin的表达情况.结果:45例癌组织Ezrin异常表达率84.4%(38/45),癌旁正常肾组织Ezrin异常表达率40%(18/45),Ezrin在癌组织中的异常表达明显高于癌旁正常肾组织(χ2=18.9,P<0.005);45例癌组织E-cadherin异常表达率73.3%(33/45),癌旁正常肾组织E-cadherin异常表达率35.6%(16/45),E-cadherin在肾透明细胞癌中的异常表达明显高于癌旁正常肾组织(χ3=12.9,P<0.05);两者呈负相关;Ezrin和E-cadherin的表达与淋巴结转移、静脉瘤栓形成有关(P<0.05),与患者年龄、性别、肿瘤大小、病理分期无相关性(P>0.05).结论:Ezrin和E-cadherin与肾透明细胞癌的浸润转移有关,可能作为预测肾癌转移和判断预后的肿瘤标志物.     

MUC1、E-cadherin在肝门胆管癌组织中的表达及其临床意义

目的检测黏蛋白1(MUC1)、E-钙黏附素(E-cadherin)在肝门胆管癌组织中的表达,探讨其在肝门胆管癌发生、发展过程中的作用。方法取青岛大学医学院附属医院2006年6月至2009年6月手术切除且临床随访资料完整的54例肝门胆管癌的石蜡包埋组织标本。采用免疫组化S-P法染色,检测石蜡切片中MUC1与E-cadherin的表达情况,应用SPSS13.0统计软件对实验数据进行统计学处理。结果 (1)MUC1、E-cadherin在肝门胆管癌组织中高表达率分别为68.5%、33.3%,正常胆管组织中MUC1、E-cadherin高表达率分别为20%、80%。肝门胆管癌组织和正常胆管组织之间MUC1、E-cadherin的表达比较,差异具有显著性(P<0.05)。(2)肝门胆管癌组织中MUC1、E-cadherin蛋白的表达均与肿瘤的侵袭转移能力、患者的生存期密切相关(P<0.05)。结论 MUC1、E-cadherin可能参与肝门胆管癌的发生、发展、转移过程。     

β-catenin在口腔鳞状细胞癌中的表达及临床意义

目的 检测口腔鳞癌中上皮间质化(EMT)相关蛋白和β-连环素(β-catenin)的表达初步探讨其意义.方法 用免疫组法检测32例口腔鳞癌组织及正常组织中上皮标记物:上皮-钙黏蛋白(E-cad)及细胞角蛋白(CK)、p-catenin的表达.结果 口腔鳞癌组β-catenin表达明显高于正常组织组(P＜0.05),CK及E-cadherin表达明显低于正常组织组(P＜0.05);β-catenin在T4+T3组的表达显著高于T1+T2组(P＜0.05),E-eadherin的表达明显低于T1+ T2组(P＜0.05);有淋巴结转移组β-catenin表达高于无淋巴结转移组(P＜0.05),E-cadherin、CK表达低于无淋巴结转移组(P＜0.05).结论 口腔鳞癌组织中存在EMT现象,E-cadherin、CK及-catenin在OSCC与正常组织表达中有差异,β-catenin可能参与OSCC组织发生EMT的进程,促进口腔鳞癌浸润及转移.     

E盒结合锌指蛋白 2促进肺腺癌细胞 A549迁移的作用研究

目的 研究转录因子E盒结合锌指蛋白2(zinc finger E-box-bindingprotein,ZEB2)在肺癌组织中的表达及促进结肺癌细胞A549迁移的作用.方法 研究起止时间为2018年3月至2019年5月.采用免疫组化法检测肺癌组织及癌旁组织中ZEB2蛋白的表达情况;Transwell法检测干扰或过表达ZEB2对A549细胞迁移作用的影响;RT-PCR和蛋白质印迹法(Western blotting)检测ZEB1对A549细胞中转移相关分子-E钙黏素(E-cadherin)表达的影响.结果 与对照组相比,干扰ZEB2表达可抑制A549细胞的迁移能力,对照组穿过Transwell小室的细胞数量为(37.6±8.1)个,干扰ZEB2组为(12.3±3.2)个;相反,过表达ZEB2可促进A549细胞的迁移能力,对照组为(48.3±4.2)个,过表达ZEB2组为(129.6±12.1)个;干扰ZEB2可促进E-cadherin基因和蛋白的表达,过表达ZEB2则可抑制E-cadherin基因和蛋白的表达;ZEB2在肺癌组织中的表达明显高于在癌旁组织中的表达.结论 ZEB2在肺癌组织中高表达并可促进肺腺癌细胞迁移能力.     

食管鳞癌组织中CD44v6与E-钙黏蛋白表达及其临床意义

目的 探讨食管鳞癌组织CD44v6与E-钙黏蛋白(E-cad)表达与其临床病理特征的关系.方法 采用免疫组化法检测48例食管鳞癌(A组)、23例糜烂性食管炎(B组)和24例正常食管黏膜组织(C组)CD44v6和E-cad的表达,分析其表达与食管鳞癌临床病理特征的关系.结果 A组CD44v6表达明显高于B、C组,而E-cad表达明显低于B、C组(P＜0.05).CD44v6和E-cad的表达与食管鳞癌浸润深度和淋巴结转移密切相关(P＜0.05).食管鳞癌组织中CD44v6和E-cad表达水平呈负相关(r=-0.580,P＜0.05).结论 联合检测病变组织中CD44v6与E-cad的表达有望成为食管鳞癌筛查及预后判断的辅助指标.     

“三阴”型与非“三阴”型乳腺癌临床特征与E-钙黏蛋白表达的临床意义

目的通过回顾性分析总结"三阴"型乳腺癌与非"三阴"型乳腺癌患者的临床病理特征、生物学特点以及两组E-钙黏蛋白表达情况来探讨其表达与乳腺癌转移及预后的相关性,以指导临床对于预后的判断。方法随机抽取笔者所在医院收治的经病理组织学确诊的乳腺癌患者病理组织113例,所有资料临床数据可溯源,且随访完整。采用统计软件对"三阴"型与"非三阴"型乳腺癌患者的临床病理学特点、复发转移、月经状况、E-钙黏蛋白表达等方面进行分析。结果"三阴"型与非三阴型乳腺癌患者相比,E-钙黏蛋白表达无明显统计学差异。但E-钙黏蛋白低表达者,生存曲线有下降趋势。logistic回归分析显示E-钙黏蛋白表达与腋窝淋巴结早期转移、远处转移部位多少、绝经状态以及ER表达状态差异有统计学意义(P<0.05);同时用COX风险模型多因素分析显示,本组患者腋窝淋巴结数目、远处转移部位多少为三阴及非三阴性乳腺癌预后不良的独立危险因素。Kaplan-Meier生存曲线显示ER阳性且E-钙黏蛋白低表达的非三阴乳腺癌生存时间缩短,差异有统计学意义(P<0.05)。结论"三阴"型乳腺癌与非"三阴"型乳腺癌E-钙黏蛋白表达低者预示生存时间缩短,同时E-钙黏蛋白表达与ER表达呈负相关性(P<0.05)。E-钙黏蛋白表达对于乳腺癌预后具有指导性意义。     

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.     

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.     

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.     

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.     

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.