4-羟基壬烯醛诱导支气管上皮细胞凋亡

目的 探讨4-羟基壬烯醛(4-HNE)对支气管上皮细胞(16-HBE)凋亡的诱导作用及其机制.方法 将支气管上皮细胞(16-HBE)分为空白对照组、10 μmol/L、30 μmol/L、50 μmol/L4-HNE作用4 h组,观察4-HNE作用4 h后的细胞凋亡情况.Western印迹方法检测磷酸化(p-)SAPK-JNK和caspase-3蛋白表达的情况.结果 细胞经30 μmol/L、50 μmol/L 4-HNE作用后,姬姆萨染色可见明显细胞凋亡改变.对照组、10 μmol/L、30 μmol/L、50μmol/L 4-HNE组的AnnexinV-PI染色凋亡细胞数分别为1.94±1.03,2.03±1.04,43.36±1.3,65.92±3.45.30 μmol/L和50 μmol/L 4-HNE组与对照组及10 μmol/L 4-HNE组比较,差异有统计学意义(P＜0.01).各组p-SAPK-JNK蛋白表达差异无统计学意义(P＞0.05).30 μmol/L、50 μmol/L 4-HNE刺激组caspase-3的表达较对照组和10 μmol/L4-HNE组差异有统计学意义(P＜0.01).结论 30、50 μmol/L 4-HNE可通过caspase-3的激活引起支气管上皮细胞的凋亡.     

红霉素对支气管上皮细胞转录因子c-Jun和核因子-κB表达的影响

探讨红霉素对4-羟基壬烯醛(4-HNE)引起的支气管上皮细胞(16-HBE)核转录因子c-Jun及NF-κB的影响。将人支气管上皮细胞分为4-HNE组(10μmol/L 4-HNE)红霉素+4-HNE组、对照组,在4-HNE刺激细胞2、4、8及12h后,检测c-Jun及NF-κB的变化。结果表明,4-HNE和对照组比较,c-Jun、NF-κB自2h后各时间段两组差异有统计学意义,P均<0.05。红霉素+4-HNE组在4-HNE刺激2h后,c-Jun及NF-κB的表达较4-HNE组,差异有统计学意义,P均<0.01。4-HNE促进支气管上皮细胞c-Jun及NF-κB的表达。红霉素可抑制4-HNE诱导的c-Jun及NF-κB的表达。     

Alpha-熊果苷激活凋亡信号通路对人急性T细胞白血病细胞TIB-152异常增殖的调节作用

目的:本文旨在探究alpha-熊果苷对人急性T细胞白血病细胞TIB-152增殖和凋亡的影响及其分子机制。方法:TIB-152细胞分为4组:TIB-152 (对照组); alpha-熊果苷(10、20、50μmol/L)组。CCK-8检测细胞增殖。流式细胞术分析细胞凋亡。蛋白印迹检测B细胞淋巴瘤2(Bcl-2),Bcl-2相关蛋白X(Bax),Cleaved caspase-3和Cleaved caspase-9表达。结果:低浓度(50μmol/L)的alpha-熊果苷对TIB-152没有明显的细胞毒性,高浓度(50μmol/L)的alpha-熊果苷会对TIB-152产生细胞毒性。50μmol/L的alpha-熊果苷组细胞增殖倍数明显低于对照组(P0. 01)。与对照组相比,50μmol/L的alpha-熊果苷组细胞凋亡率显著升高(P0. 01)。而且,50μmol/L的alpha-熊果苷组Bax/Bcl-2比值显著高于对照组(P0. 01)。同时,50μmol/L的alpha-熊果苷组Cleaved caspase-3和Cleaved caspase-9表达也显著高于对照组(P0. 01)。结论:Alpha-熊果苷可激活凋亡信号通路抑制人急性T细胞白血病细胞TIB-152细胞增殖,促进细胞凋亡。     

奥氮平对鱼藤酮诱导PC12细胞凋亡的保护作用

探讨非典型抗精神病药物奥氮平对鱼藤酮诱导神经元凋亡的可能保护作用及其机制。以NGF诱导后的PC12细胞作为细胞模型,采用鱼藤酮诱导细胞凋亡。用不同浓度奥氮平、氟哌啶醇预处理后,观察鱼藤酮对PC12细胞的作用,分别用噻唑蓝(MTT)法检测细胞活性、流式细胞仪检测细胞凋亡率、Hoechst33342染色观察细胞形态学改变,并对二者的结果进行比较。鱼藤酮以剂量依赖的方式杀死PC12细胞。鱼藤酮(6μmol/L)作用后,奥氮平(50μmol/L)组预处理48h的细胞活力显著高于对照组(无药物预处理)(P<0.05);鱼藤酮(4、6、8μmol/L)作用后,氟哌啶醇组(20、40、60μmol/L)的细胞活力均低于对照组。流式细胞仪检测结果显示,对照组、氟哌啶醇(20μmol/L)组、奥氮平(50μmol/L)组、空白对照组(无药物预处理以及鱼藤酮处理)的细胞凋亡率依次为(32.2±1.3)%、(42.1±1.0)%、(14.0±1.0)%和(1.3±0.3)%。Hoechst33342染色结果显示,对照组每个视野多见凋亡细胞,细胞核裂解为碎块,氟哌啶醇组更明显;奥氮平组凋亡细胞数量较氟哌啶醇组及对照组为少。结果提示奥氮平对鱼藤酮诱导PC12细胞的凋亡具有保护作用,这可能是奥氮平和氟哌啶醇在精神分裂症病人应用中有不同的治疗效果和副作用的部分机制。     

Smoothelin在氯化镉致16HBE细胞损伤中的作用

目的 研究氯化镉致16HBE细胞损伤后smoothelin基因mRNA表达变化,探讨SMTN在镉致细胞损伤中的作用.方法 分别用10、20、30、40 μmol/L CdCl2 处理16HBE细胞24 h,用30 μmol/L CdCl2处理16HBE细胞12、24、48和72 h,利用MTT法检测细胞存活率,qRT-PCR法检测细胞SMTN基因表达变化.结果 与CdCl2浓度为0 μmol/L对照组相比,10、20、30、40 μmol/L组细胞存活率分别为(84.2±9.7) %、(54.6±6.0) %、(30.2±2.9)%、(10.9±2.1) %,皆有显著性差异(P<0.01);而20、30、40 μmol/L组细胞SMTN mRNA相对表达分别2.943±0.212,10.602±1.330,43.782±4.571,与CdCl2浓度为0 μmol/L对照组比较有显著性差异(P<0.01),且随着CdCl2染毒剂量的上升,SMTN表达逐渐升高.与CdCl2浓度为0 μmol/L对照组比较,30 μmol/L CdCl2处理16HBE细胞12、24、48和72 h,细胞生存率分别为(76.3±7.2) %,(35.2±4.0) %,(18.8±2.1) %,(7.0±0.9) %,有显著性差异(P<0.01),12、24、48和72 h处理细胞SMTN mRNA相对表达分别为11.419±1.441,12.030±1.402,10.420±1.114,8.953±0.987,有显著性差异(P<0.01).结论 SMTN mRNA在氯化镉处理细胞中表达明显升高,有明显的剂量-反应关系,可能在镉致细胞死亡或凋亡中发挥作用.     

BMS-345541对人骨肉瘤细胞MG63凋亡及其作用机制

目的研究BMS-345541对人骨肉瘤细胞MG63凋亡的影响及其可能的机制。方法以0、2、4、6、8、10μmol/L BMS-345541处理MG63细胞24、48 h后,用CCK-8法检测细胞存活率。用0、2、4、8μmol/L药物作用细胞24 h后,以PI染色法观察细胞凋亡情况、流式细胞仪检测细胞凋亡。以同样浓度作用细胞48 h,Western-blot检测cleaved Caspase-3蛋白表达情况。结果 (4-10)μmol/L的BMS-345541均可抑制MG63细胞的增殖,其抑制效应呈剂量-时间依赖性,48 h最低存活率只有(0.412±0.024)(P0.05)。PI染色荧光显微镜观察结果发现:随药物浓度增高,相同视野下正常细胞数逐渐降低,凋亡细胞数逐渐增高。流式细胞仪分析:0、2、4、8μmol/L的作用BMS-345541 24 h后,凋亡率分别为(5.2±0.78)%、(5.82±0.82)%、(8.86±1.71)%、(11.01±2.69)%,与对照组相比,8μmol/L组差异有统计学意义(P0.05)。Western blot结果显示MG 63细胞中的cleaved caspase-3蛋白表达量上调,与对照组相比,2、4、8μmol/L组差异均有统计学意义(P0.05)。结论 BMS-345541可抑制MG63细胞增殖,并诱导其发生凋亡,其作用机制可能与cleaved caspase-3表达上调有关。     

阻断MEK1上调支气管上皮细胞谷氨酰半胱氨酸合成酶的表达

目的 探讨MEK1信号通路与支气管上皮细胞(16-HBE)谷氨酰半胱氨酸合成酶(γ-GCS)表达的关系.方法 应用MEK1抑制剂PD98059 50μmol/L分别孵育16-HBE 2、8、16及24 h.用Western印迹方法和荧光定量PCR检测细胞γ-GCS重链蛋白和mRNA的表达.用显色方法检测细胞内谷胱甘肽(GSH)的含量.用Western印迹方法检测细胞c-jun的水平.结果 经PD98059孵育4、8、16及24 h后,γ-GCS重链蛋白和mRNA的表达和细胞内GSH的含量较对照组均增加.各时间段c-jun表达较各对照组减少.结论 在支气管上皮细胞中MEK1抑制剂PD98059对16-HBE的γ-GCS和GSH有明显的上调作用.阻断激活蛋白-1(AP-1)途径不能减少γ-GCS和GSH的合成.     

土荆皮乙酸促进喉癌细胞系HEp-2凋亡

目的本文观察土荆皮乙酸(PAB)对人喉表皮样癌细胞系2(HEp-2)的增殖和凋亡的影响。方法细胞分组及处理:以0、0.5、1、2、4、8和16μmol/L的PAB分别处理细胞24、48和72 h;MTT法检测细胞活性;流式细胞仪检测细胞凋亡;Western blot和qPCR检测细胞Bcl-2、Bax和caspase-3蛋白及mRNA表达;免疫组化检测细胞PARP和c-PARP蛋白的表达。结果 PAB呈时间-浓度依赖性抑制HEp-2增殖。与对照组比较,4和8μmol/L PAB组HEp-2细胞凋亡率均显著升高(P<0.01);4和8μmol/L PAB组HEp-2细胞的Bcl-2和PARP表达均显著下降(P<0.05);Bax、caspase-3和c-PARP的表达均显著升高(P<0.05)。结论 PAB可激活线粒体凋亡途径,诱导HEp-2细胞凋亡。     

松香酸通过诱导自噬减轻AGEs诱导的心肌H9c2细胞凋亡和内质网应激反应

目的:本文旨在探索松香酸(abietic acid,AA)对晚期糖基化终末产物(advanced glycosylation end products,AGEs)诱导的心肌H9c2细胞凋亡和内质网应激的影响及其相关机制。方法:H9c2细胞分为5组:对照组加入生理盐水处理24 h;AGEs处理组加入AGEs(100 mg/L)处理24 h;AGEs+AA(10、25和50μmol/L)组同时加入AGEs(100 mg/L)和AA(10、25和50μmol/L)处理24 h。MTT法检测H9c2细胞活力。Western blot分析肌红蛋白(myoglobin,Mb)、肌酸激酶MB同工酶(creatine kinase MB isoenzyme,CK-MB)、心肌肌钙蛋白I(cardiac troponin I,c Tn I)、C/EBP同源蛋白(C/EBP homologous protein,CHOP)、cleaved caspase-12、GADD34、Bi P、LC3、P62和beclin 1的蛋白水平。ELISA检测乳酸脱氢酶(lactate dehydrogenase,LDH)活性。流式细胞术分析细胞凋亡。结果:低浓度(低于50μmol/L)的松香酸对H9c2细胞活力无明显影响,高浓度(高于50μmol/L)的松香酸会降低H9c2细胞活力。AGEs组Mb、CK-MB和c Tn I蛋白表达及LDH的水平明显高于对照组(P0.05);与AGEs组相比,AGEs+AA(10、25和50μmol/L)组Mb、CK-MB和c Tn I的蛋白表达及LDH的表达水平明显降低(P0.05)。松香酸(10、25和50μmol/L)可抑制AGEs诱导的心肌细胞凋亡、CHOP和cleaved caspase-12蛋白水平的升高及GADD34和Bi P表达的降低(P0.05)。而且,松香酸(10、25和50μmol/L)可抑制AGEs诱导的心肌细胞LC3-Ⅱ/LC3-Ⅰ比值和beclin 1表达的降低及P62表达的升高(P0.05)。自噬抑制剂3-甲基腺嘌呤可逆转松香酸对心肌细胞LC3、Mb、cleaved caspase-12和Bi P蛋白水平的影响(P0.05)。结论:松香酸通过诱导自噬减轻AGEs诱导的心肌H9c2细胞凋亡和内质网应激反应。     

肽基脯氨酰顺反异构酶抑制剂胡桃醌对宫颈鳞癌SiHa细胞凋亡的作用

目的:探讨肽基脯氨酰顺反异构酶抑制剂胡桃醌对宫颈鳞癌Si Ha细胞增殖和凋亡的影响及其促凋亡的机制。方法:选取处于对数生长期的Si Ha细胞,将其分为空白对照组和不同剂量(10、20、50、80及100μmol/L)胡桃醌给药组,共6组。采用MTT法观察胡桃醌对Si Ha细胞的抑制作用,并计算出半数抑制浓度(IC50=20.4μmol/L),依据IC50确定胡桃醌的有效浓度;选取与IC50接近的浓度(20μmol/L)通过Hoechst 33258及流式细胞术测定胡桃醌对Si Ha细胞凋亡的影响,Western blot检测凋亡相关蛋白caspase-3、8、9以及抑癌基因PTEN的蛋白水平。结果:MTT实验结果显示,与对照组比较,各给药组对细胞活力的抑制作用明显,差异有统计学意义(P0.05);Hoechst 33258检测表明,20μmol/L胡桃醌处理细胞12 h后可出现明显的细胞核典型凋亡细胞形态,流式细胞术检测结果说明胡桃醌可诱导Si Ha细胞出现早期凋亡;Western blot检测显示与正常对照组相比,20μmol/L胡桃醌处理细胞12 h后,cleaved caspase-3、8、9及PTEN的蛋白水平明显增加。结论:胡桃醌可以抑制Si Ha细胞的活力,并诱导细胞凋亡,其机制主要是通过抑制caspase途径并增加抑癌基因的表达。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.     

A comparative study of the effects of dimebon,obsidan, finoptin,and cordaron on the functional state of ischemic focus and size of necrotic zone in experimental myocardial infarction

Dimebon, an antihistamine agent, exerts a moderate antianginal effect, improving the function of ischemic focus in the myocardium and decreasing the necrotic zone in experimental myocardial infarction. Dimebon is less active than obsidan, finoptin (except for the size of the necrotic zone), and cordaron. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 12, pp. 642–644, December, 1996     

Effects of sex steroid hormones on lipid peroxidation and glutathione antioxidant system in rat skin

Effects of estradiol and testosterone on the intensity of lipid peroxidation and contents of glutathione redox system components in the dermis and epidermis of rat skin were studied. Only estradiol induced considerable dose-dependent and tissue-specific biphasic antioxidant effects on the skin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 12, pp. 663–666, December, 1999     

Adhesion and growth of CaCo2 cells on surface-modified PEEK substrata

A series of surface-functionalized poly(ether ether ketone) (PEEK) films has been prepared by selective wet-chemistry; they are hydroxylated polymer (PEEK-OH) obtained by reduction, aminated polymer (PEEK-[]-NH2) prepared by coupling a diisocyanate reagent to PEEKOH (PEEK-[]-NCO) followed by hydrolysis, and carboxylated and aminocarboxylated polymers (PEEK-[]-GABA and PEEK-Lysine) resulting from the coupling of aminoacids to PEEK-[]-NCO. The aminated and carboxylated substrata promoted the adhesion and growth of CaCo2 cells in the presence of serum. Fibronectin (FN), an extra-cellular matrix protein, has been covalently fixed and/or adsorbed on various PEEK substrata, in the presence or not of a polymeric surfactant (Pluronic F68). The performances of the FN-grafted substrata (PEEK-[]-FN(1) and PEEK-[]-FN(2)) were significantly higher than those of reference substrata simply coated with FN (PEEK-OH(+FN)(1) and (2), PEEK-[]-NH2(+FN)(1) and (2)), considering the adhesion and spreading of CaCo2 cells in the absence of serum. Moreover, the stability of the adherent cells on the FN-adsorbed substrata dramatically depended on the experimental conditions applied during the PEEK coating with FN.