川陈皮素对人胃癌细胞SGC-7901抑制作用的实验研究

目的研究川陈皮素的体外抗人胃癌细胞SGC-7901作用。方法以不同浓度（1.25、2.5、5、10、20、40、80、160mg/L）的川陈皮素作用于SGC-7901细胞,分别用MTT法、细胞生长曲线研究其对SGC-7901的增殖抑制作用。结果MTT显示川陈皮素浓度在2.5～80mg/L时,对SGC-7901细胞的抑制率为19%～90%,IC50值为（21.28±4.17）mg/L。生长曲线提示川陈皮素对SGC-7901细胞的抑制作用呈明显时效和量效关系。结论川陈皮素对人胃癌细胞SGC-7901有较强的增殖抑制作用。     

AKT体内外抗肝癌作用及机理的初步研究

目的：观察AKT对人肝癌细胞SMMC-7721及小鼠H22肝癌移植性肿瘤的抑制作用，并探讨以紫草总色素为主要成分，制备而成的AKT的抗肿瘤作用机制。方法：用MTT法分析AKT对人肝癌细胞SMMC-7721的增殖抑制作用绘制作用生长曲线；建立小鼠H22肝癌移植性实体瘤模型，通过绘制瘤块生长曲线及计算肿瘤抑制百分率评价体内抑瘤效果，流式细胞术检测不同剂量AKT作用SMMC-7721细胞48h后细胞凋亡率及细胞周期变化，并检测Bax及Bcl-2蛋白的表达情况；RT-PCR检测AKT作用SMMC-7721细胞24h后，bcl-2 mRNA及baxmRNA的表达情况。结果：（1）MTT提示AKT对SMMC-7721细胞具有显著抑制作用；（2）体内实验表明，AKT对小鼠H22肝癌移植性肿瘤有一定的抑制作用。（3）Giemsa染色后在光镜下可见AKT给药组多数细胞出现形态改变，胞体变小，胞质浓缩拉长，呈拉丝状，核质比增大，核膜完整，核固缩，染色质不均一或边集，胞浆内较多空泡的典型凋亡特征；Hoechst 33258染色后细胞核出现细胞核固缩，出现凋亡小体等明显的凋亡形态学变化；流式细胞术检测显示AKT作用SMMC-7721细胞后，中、高剂量组均检测到明显亚G1凋亡峰；给药组S期细胞明显降低，G2／M期细胞明显增多，细胞周期阻滞于G2／M期；药物处理后Bcl-2及Bax的表达均下调，且Bcl-2／Bax值降低；RT-PCR检测结果显示给药组bcl-2 mRNA及bax mRNA表达水平均出现下调，bcl-2／bax比值降低；体内实验瘤组织免疫组化结果显示给药组Bcl-2表达下调，Bax及Caspase-3表达均出现上调。结论：AKT对人肝癌SMMC-7721细胞具有明显体外抗增殖作用，对小鼠移植性肿瘤H22也呈现了明显的抑制作用。其效应机制可能与阻滞细胞周期于G2／M期，下调bcl-2 mRNA及Bcl-2蛋白表达，上调Caspase-3表达，从而诱导肿瘤细胞凋亡，抑制肿瘤细胞增殖有关。     

楤白皮总皂苷体内外的抗肿瘤作用

目的:研究楤白皮总皂苷的体内外抗肿瘤活性。方法:采用MTT体外测定楤白皮总皂苷对小鼠B16黑色素瘤、小鼠H22肝癌细胞和小鼠FBL3红白血病细胞的增殖抑制作用;采用小鼠移植性肿瘤S180和H22观察楤白皮总皂苷的体内抑瘤活性。结果:楤白皮总皂苷体外对B16细胞、FBL3细胞的IC50分别为0.077 4 g.L-1和0.199 g.L-1;在0.02～3.2 g.L-1范围内,对H22细胞体外抑制率均为80%以上。在100、200、300 mg.kg-1剂量下,楤白皮总皂苷对S180小鼠肉瘤的抑瘤分别为16.9%、37.1%和27.0%,对H22小鼠肝癌的抑瘤率分别为23.7%、10%和13.4%。结论:楤白皮总皂苷在体内、外均具有一定的抗肿瘤活性。     

黄连解毒汤体内外抗肿瘤作用的实验研究

目的：观察黄连解毒汤的体内、体外抗肿瘤作用。 方法：采用小鼠肉瘤S180和小鼠前胃癌MFC等移植性肿瘤模型进行体内实验,通过检测抑瘤率、胸腺指数、脾脏指数等指标观察黄连解毒汤的体内抑瘤作用及对免疫器官的影响。并用MTT方法检测黄连解毒汤对小鼠S180、小鼠MFC、人胃癌SGC-7901、人肝癌SMMC-7721等4种瘤株的抑制作用。结果：黄连解毒汤大、中剂量组中对S180荷瘤小鼠有抑制作用,大剂量组对MFC荷瘤小鼠有抑制作用,抑瘤率分别为48.38%、33.77%、30.74%;对S180、MFC、SGC-7901和SMMC-7721细胞均有一定的细胞毒作用, IC50分别为99.73 mg?L-1、84.47 mg?L-1、153.32 mg?L-1和102.87 mg?L-1。结论：黄连解毒汤体内对S180、MFC小鼠移植瘤有一定的抗肿瘤活性,体外对4种肿瘤细胞也具有抑制作用。     

基因重组心肌肌钙蛋白Ⅰ融合蛋白的抗肿瘤效应

目的研究基因重组心肌肌钙蛋白I与人工短肽的融合蛋白(CIS)对肿瘤生长的作用。方法用MTT法观察CIS体外对人脐静脉内皮细胞(HUVEC)生长的作用。利用鸡胚绒毛尿囊膜模型观察CIS对新生血管生长的影响。用6种小鼠肿瘤异位可移植模型观察CIS在体内对肿瘤生长的作用。结果 CIS对HUVEC细胞增殖具有明显抑制作用,并呈剂量依赖关系;鸡胚绒毛尿囊膜实验显示,CIS浓度为5、10 mg·L~(-1)时,新生血管生成的数量明显减少;荷瘤鼠体内异位移植模型实验显示:CIS(10 mg·kg~(-1))处理组肿瘤生长缓慢,瘤体明显小于模型对照组,对S180肿瘤瘤重抑制率85.3%,对Lewis肺癌肿瘤瘤重抑制率87.0%,对H22肝癌肿瘤瘤重抑制率84.2%,对人小细胞肺癌H446肿瘤瘤重抑制率60.42%,对人可移植性肝癌SMMC7721肿瘤瘤重抑制率61.62%,对人胃低分化腺癌BGC823肿瘤瘤重抑制率为41.84%。结论 CIS在体外抑制HUVEC细胞的生长,在鸡胚绒毛尿囊膜实验中,CIS对新生血管生成有明显的抑制作用。在体内,CIS融合蛋白可有效抑制小鼠可移植肿瘤细胞的生长。CIS抗肿瘤效应很可能是通过抑制肿瘤组织中血管内皮细胞的增殖,进而减少肿瘤组织中新生血管生成的数量而达到的。     

骆驼蓬硷抗癌作用的研究

目的 :研究骆驼蓬硷对小鼠移植性肿瘤体内及体外肿瘤细胞的抗癌试验。方法 :体内抑瘤实验采用S -1 80 ,肝癌H2 2 及艾氏腹水癌等荷瘤小鼠、体外实验采用Hela细胞和S -1 80细胞。结果 :骆驼蓬硷对小鼠移植性肿瘤的抑制率在 2 8 94 % -4 6 77%之间 ,对肿瘤细胞的平均生长抑制率在 83 4 1 % -92 30 %之间。结论 :骆驼蓬硷对肿瘤细胞体内抑瘤试验、体外细胞毒试验均有明显的抑制作用。     

广西眼镜蛇毒蛋白Natrin在体外诱导人肝癌细胞SMMC-7721凋亡作用的研究

目的观察广西眼镜蛇毒蛋白Natrin在体外对人肝癌SMMC-7721细胞的增殖抑制作用及凋亡诱导作用。方法以不同浓度的Natrin作用于SMMC-7721细胞24 h后,用MTT法检测细胞的生长抑制率;AO/EB双染色法、透射电子显微镜法观察细胞凋亡、流式细胞仪检测细胞凋亡率及细胞周期。结果 Natrin对人肝癌SMMC-7721细胞有体外抑制作用,随着药物浓度的增大抑制率也随之增大,24 h半数抑制浓度IC50为138.69 mg·L-1;给药后,荧光显微镜下与透射电子显微镜下细胞呈现典型的凋亡形态改变;流式细胞仪检测到随着药物浓度的增大凋亡百分数也随之增大;Natrin能诱导SMMC-7721细胞发生S期和G2/M期阻滞。结论Natrin在体外能抑制人肝癌SMMC-7721细胞增殖并诱导其凋亡。     

辛伐他汀对荷瘤小鼠抑瘤作用的实验研究

目的研究辛伐他汀对小鼠肝癌细胞H22抑瘤作用的影响.方法采用小鼠H22肝癌细胞实体瘤模型进行体内抑瘤实验,观察荷瘤动物的生长情况和肿瘤生长曲线,测定肿瘤生长抑制率,以及生存期的改变.结果辛伐他汀对小鼠的H22实体瘤生长具有明显的抑制作用,抑瘤率达50%以上.未发现生存期的改变.结论辛伐他汀具有较强的体内抗肿瘤作用.     

D-氨基葡萄糖及其衍生物抗肿瘤活性的初步研究

目的观察氨基葡萄糖盐酸盐(GlcNH2.HCl)、氨基葡萄糖(GlcNH2)和N-乙酰氨基葡萄糖(NAG)体外抑制人肝癌细胞(SMMC-7721)生长的作用,对小鼠S180肉瘤的肿瘤抑制作用以及对免疫系统的影响并探讨其作用机制。方法采用MTT法检测不同浓度的单糖对SMMC-7721细胞生长的影响,倒置显微镜观察细胞形态,琼脂糖凝胶电泳进行DNA断裂分析,流式细胞仪检测对细胞周期的影响。采取灌胃给药的方式,观察GlcNH2.HCl对S180小鼠瘤重、胸腺重和脾重以及荷瘤小鼠淋巴细胞转化率的影响。结果GlcNH2.HCl和GlcNH2能明显抑制肝癌细胞SMMC-7721的生长,且存在剂量依赖性,在500μg.mL-1浓度下,Glc-NH2.HCl和GlcNH2的抑制率为50.24%和52.19%,在1000μg.mL-1浓度下的抑制率分别为82.21%和83.2%。GlcNH2.HCl对SMMC-7721细胞存在周期特异性,可以使细胞发生S期阻滞。NAG对肝癌细胞的生长没有明显抑制作用。GlcNH2.HCl在125~500mg.kg-1的剂量范围内,对小鼠S180肉瘤均有一定的抑制作用,平均抑瘤率在27.84%~34.02%之间,其中250 mg.kg-1剂量的抑制作用最强,在该剂量范围下,GlcNH2.HCl对荷瘤小鼠具有明显增加胸腺指数和脾指数的作用,同时促进荷瘤小鼠脾脏T淋巴细胞转化,无明显毒副作用。结论GlcNH2.HCl体外呈剂量依赖性抑制人肝癌细胞SMMC-7721的生长,体内可能是通过直接杀伤肿瘤细胞的细胞毒作用和提高S180肉瘤小鼠细胞免疫水平来发挥抑瘤作用。     

香参软胶囊对小鼠肝癌的抑制作用研究

目的：研究香参软胶囊对小鼠H22移植性肝癌腹水及其对SMMC7721荷瘤裸鼠的抗肿瘤作用。方法：昆明种小鼠腹腔注射H22肝癌细胞,建立肝癌腹水模型,观察香参软胶囊高（720mg·kg-1）、中（360mg·kg-1）、低（180mg·kg-1）剂量组灌胃给药对H22移植性肝癌腹水小鼠体征及生命延长率的影响;裸鼠右腋窝皮下接种SMMC7721细胞悬液,待察瘤块成形后给药。观察香参软胶囊高（720mg·kg-1）、中（360mg·kg-1）、低（180mg·kg-1）剂量组灌胃给药对SMMC7721荷瘤裸鼠肿瘤生长及其瘤重的影响。结果：与H22移植性小鼠肝癌腹水模型组比较,香参软胶囊高剂量组显著抑制腹围增长（P<0.01）,延长小鼠生存时间（P<0.01）;香参软胶囊中剂量组显著延长小鼠生存时间（P<0.05）。与SMMC7221荷瘤裸鼠比较,香参软胶囊各剂量组平均瘤重及肿瘤体积均小于模型组;香参软胶囊高剂量组能极显著抑制SMMC7721荷瘤裸鼠肿瘤生长,同时高剂量组对肿瘤生长的抑制作用略优于平消胶囊组。结论：香参软胶囊显著H22肝癌小鼠腹水生长,延长小鼠存活时间;香参软胶囊对裸鼠SMMC7721移植性瘤具有明显抑制作用。结果表明香参软胶囊具有较明显的抗肝癌作用。     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.