Celiac disease-specific and inflammatory bowel disease-related antibodies in patients with recurrent aphthous stomatitis

The etiology of recurrent aphthous stomatitis (RAS) remains unknown. RAS can be presented as primary, idiopathic condition and as a secondary RAS, which is associated with a systemic disease. The aim of our study was to evaluate the presence and concentrations of antibodies specific for celiac disease (CeD) and antibodies related to inflammatory bowel diseases (IBD) in patients with RAS without gastrointestinal symptoms. Antibodies against tissue transglutaminase (anti-tTG), deaminated gliadin peptides (DGP), deaminated gliadin-analogous fragments (anti-GAF-3X) and Saccharomyces cerevisiae (ASCA) were determined by ELISA and antineutrophil cytoplasmic antibodies (ANCA) by indirect immunoflurescence (IIF) in 57 patients with RAS and 60 control subjects. The prevalence of CeD specific antibodies did not differ between RAS patients and controls. However, the concentrations of IgA anti-tTG, IgA anti-GAF-3X antibodies in patients with RAS were significantly higher compared to controls (p?=?0.002 and p?=?0.04 respectively). Histological changes consistent with CeD were confirmed by duodenal biopsy in one RAS patient with highly positive IgA anti-tTG, anti-GAF-3X and anti-DGP antibodies. Higher prevalence along with higher concentrations of IgG ASCA were found in RAS patients compared to controls (p?<?0.01). Patients with positive IgG ASCA in the absence of clinical symptoms decided not to pursue any further testing. Dysfunction of oral mucosa and the exposure to various antigens might be a reason for the loss of tolerance resulting in increased production of autoantibodies. It seems likely that antibodies are markers of aberrant immune response, rather than key effectors involved in the pathogenesis of the disease.     

慢性丙型肝炎患者氧化损伤的研究

目的 探讨慢性丙型肝炎(CHC)患者体内氧化损伤的情况.方法 52例CHC患者,按丙氨酸转氨酶(ALT)水平分为A组(ALT上升组)和B组(ALT正常组).正常对照组为20例健康志愿者.利用酶联免疫吸附法(ELISA)测定研究对象血清黄嘌呤氧化酶(XOD),丙二醛(MDA),氧化型谷胱甘肽(GSSG),谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽巯基转移酶(GST),谷胱甘肽还原酶(GR)及维生素C(Vc)水平,并作出统计分析.结果 CHC患者血清XOD,MDA,GST和GR水平较正常对照组显著升高,而GSH,GSH-Px和Vc水平则明显降低.同时,A组患者血清XOD,MDA,GSSG,GST及GR水平较B组患者显著上调,而GSH,GSH-Px和Vc水平则显著下调.在CHC患者中,血清XOD,MDA,GSSG,GST水平与ALT水平呈正相关,血清GSH,GSH-Px,Vc与ALT水平呈负相关;血清XOD,MDA,GSSG,GR,GST水平与AST水平呈正相关,血清GSH-Px水平与AST水平呈负相关;血清GR水平与GGT水平呈正相关,血清GSH水平与GGT水平呈负相关;血清MDA,GR水平与AKP水平呈正相关.在CHC组中,仅血清XOD水平与血清HCV RNA水平间存在正相关关系.结论 CHC患者体内存在一定程度的氧化损伤,随血清ALT水平的升高,机体氧化损伤程度进一步加重.     

Oxidative stress and endothelial damage in patients with asymptomatic carotid atherosclerosis

It is know that oxidative stress can be able to induce cytotoxicity of blood cells, stimulate release of inflammatory cytokines, and induce the production of growth factors. The aim of this study was to investigate oxidative stress and endothelial dysfunction in patients with asymptomatic carotid artery disease and healthy controls. Native low-density lipoproteins, oxidised low-density lipoproteins, malondialdehyde, nitrates, glutathione peroxidase activity and endothelin-1 were determined in patients without severe (range between 30% and 50%) carotid artery stenosis. Native low-density lipoproteins, oxidized low-density lipoproteins, malondialdehyde, glutathione peroxydase, and endothelin-1 concentrations were higher in patients than in health controls (P<0.001). No difference was observed in nitrate values (P<0.8). Our results revealed oxidative stress in patients without severe carotid artery stenosis and clinical symptoms. This was shown by the elevated malondialdehyde and oxidized low-density lipoprotein levels. Received: 6 July 2000 / Accepted: 2 February 2001     

Oxidative stress and overexpression of manganese superoxide dismutase in patients with Alzheimer''s disease

Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Alzheimer's disease (AD) we examined the activity of the enzyme copper-zinc superoxide dismutase (CuZnSOD) in red blood cells, the levels of the mitochondrial inducible enzyme manganese superoxide dismutase (MnSOD) mRNA in lymphocytes, and the total radical-trapping antioxidant capacity (TRAP) in plasma of AD patients and in a group of age-matched non-demented controls. We found that CuZnSOD activity (P<0.01 vs. controls) was significantly increased as well as the MnSOD mRNA levels while the total antioxidant status (P<0.001 vs. controls) was decreased in AD patients. These findings support the role of oxidative alterations in the pathogenetic mechanism underlying AD neurodegeneration.     

氧化应激与肌萎缩侧索硬化

肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一种神经组织退化紊乱的疾病,以运动神经元受累为特点,通常在症状发现后2～3年死亡.ALS的明确病因尚不清楚,疾病的发展过程也十分多变且复杂.大量证据表明,氧化应激是该疾病发生的一个重要机制.约20％的家族型ALS是由超氧化物歧化酶1(superoxide dismutase 1,SOD1)引起的,同时,在ALS患者的脊髓及脑脊液中均发现氧化应激的标记物升高.本文简要介绍了ALS发病机制中氧化应激的重要作用及氧化应激的主要来源.     

Oxidative stress in ulcerative colitis-associated carcinogenesis

Oxidative stress is defined as an imbalance between generation of reactive oxygen species (ROS) and decreased antioxidant defense systems. Oxidative stress develops particularly in inflammatory reactions because the inflammatory cells, neutrophils, and macrophages produce large amounts of ROS. It has been known for a long time that oxidative stress in inflamed tissue can pave the way for malignant tumors, and that it is a major pathogenetic factor for the well-established correlation between inflammatory diseases and cancer. Oxidative stress has long been associated with the pathogenesis of chronic inflammatory bowel disease (IBD)-related colorectal cancer. This article provides an overview of the pathology of ROS and presents recent advances concerning the role of ROS in IBD-related colorectal carcinogenesis (Fig. 1).     

Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes

Pancreatic -cell dysfunction and insulin resistance are observed in type 2 diabetes. Under diabetic conditions, oxidative stress and ER stress are induced in various tissues, leading to activation of the JNK pathway. This JNK activation suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy.     

甲基乙二醛对Jurkat细胞氧化应激及分泌细胞因子的影响

目的:探讨甲基乙二醛(MGO)对Jurkat细胞氧化应激及分泌细胞因子的影响。方法:不同浓度MGO作用PHA预刺激的Jurkat细胞,MTT检测细胞生长,流式细胞检测细胞内活性氧(ROS),Western blot检测p38 MAPK、JNK磷酸化水平,ELISA检测TNF-α、IFN-γ。结果:15~60μmol/L MGO对Jurkat细胞生长无影响,但能使ROS呈浓度依赖性升高;N-乙酰-L-半胱氨酸(NAC)和氨基胍(AG)能明显抑制此作用。MGO作用30分钟,pp38/p38、pJNK/JNK明显升高。MGO诱导Jurkat细胞分泌TNF-α、IFN-γ;P38、JNK抑制剂及NAC能降低TNF-α、IFN-γ的分泌。结论:MGO能诱导Jurkat分泌TNF-α、IFN-γ;其机制可能通过氧化应激、P38、JNK信号通路。     

Oxidative stress in viral hepatitis and AIDS

Dominant types of viral hepatitis are presently A, B, and C with prophylactic immunization available only for A and B. Hepatitis B and C and human immunodeficiency virus (HIV) infection constitute a worldwide scourge and treatment is far from satisfactory. Each produces severe oxidative stress (OS) and secondary cellular damage of varying severity and, as in toxic hepatitis, progression and regression are dependent on redox balance between oxidation and antioxidation. Experimental and clinical studies suggest that xenobiotics and co-infections exert cumulative, detrimental effects on their pathogeneses and further deplete antioxidants. It is proposed therefore that in the clinical management of these infections and especially in their early stages, considerable benefit should accrue from antioxidant repletion at dosages substantially above recommended daily allowances (RDAs) in conjunction with a nutritious high protein diet. Because plasma zinc and selenium concentrations are very low, their replenishment by high dosages is urgent and mandatory particularly in advanced HIV infections bordering on acrodermatitis enteropathica. Also recommended is their long-term continuance at high normal levels.     

PM2.5对血管内皮细胞氧化应激和凋亡的影响及机制

目的:从大气细颗粒物PM2.5对血管内皮细胞氧化应激和凋亡的影响,研究PM2.5对血管内皮细胞的毒性。方法:体外培养血管内皮细胞株EA.hy926,用不同浓度的PM2.5染毒24 h后,用CCK-8法测细胞的活性,用DCFH-DA荧光标记法检测细胞内氧自由基生成情况,用流式细胞术检测细胞凋亡率,然后用Western blot法检测凋亡相关蛋白细胞色素C、cleaved caspase-9和cleaved caspase-3的表达变化。结果:CCK-8法结果显示PM2.5对血管内皮细胞有明显的毒性,在浓度大于25 mg/L时可使EA.hy926细胞活性显著下降;PM2.5染毒24 h后可见DCFH-DA荧光染色增强,说明细胞内有大量的氧自由基形成;流式细胞术和Western blot检测证实PM2.5可以通过上调细胞色素C表达和活化cleaved caspase-9和cleaved caspase-3而诱导EA.hy926细胞凋亡。此外,用N-乙酰半胱氨酸抑制氧自由基生成可以抑制血管内皮细胞凋亡,提示PM2.5引起的细胞凋亡与氧化应激有关。结论:PM2.5可导致血管内皮细胞氧化应激水平增强和凋亡增加,这可能是其影响心血管系统功能的机制之一。     

氧化应激损伤线粒体参与癫痫病理过程

癫痫是由脑内神经元异常放电所致,严重危害健康和影响生存质量,其致病机制主要包括:苔藓纤维芽生假说;Ca2 内流引发的细胞毒性;谷氨酸和γ-氨基丁酸及其受体结构和功能异常;氧化应激(oxidative stress,OS)损伤等.氧化应激是指活性氧(reactive oxygen species,ROS)和活性氮(reactive nitrogen species,RNS)造成的氧化损伤;即当自由基的产生过多或体内抗氧化系统出现故障,体内氧自由基代谢就会出现失衡,自由基蓄积过多,攻击机体,导致可能的损害[1].     

Oxidative stress in normal hematopoietic stem cells and leukemia

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000–2017) of English‐language literature using the terms ‘oxidative stress,’ ‘reactive oxygen species,’ ‘hematopoietic stem cell,’ and ‘leukemia.’ The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long‐term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject.     

氧化应激诱导HepG2肝癌细胞凋亡的研究(英)

目的：直接暴露细胞于活性氧能诱导发生凋亡，本文研究氧化应激诱导HepG2肝癌细胞的死亡及其机制。方法：暴露细胞于2 mmol/L过氧化氢产生氧化应激，用DNA凝胶电泳检测细胞凋亡，用荧光染色法检测细胞线粒体膜电位变化，Western blotting检测细胞浆中细胞色素c变化，fluorometric assay kit检测caspase活性变化。结果：氧化应激作用于HepG2细胞后12 h开始发生凋亡；氧化应激作用后4 h，细胞线粒体膜电位明显下降；胞浆中细胞色素c浓度呈时间依赖性增高；氧化应激作用8 h、12 h后细胞内caspase-3、caspase-9活性分别升高6.7及3.6倍，但caspase-8活性无变化。结论：氧化应激能诱导HepG2肝癌细胞发生凋亡，其途径与线粒体通路及caspase激活有关。     

Oxidative damage and HSP70 expression in masseter muscle induced by psychological stress in rats

Psychological stressors are generally associated with masseter muscle dysfunction and disorders in emotional response. In addition, oxidative states and HSP70 expression, which are involved in the physical and pathological changes of the masseter muscle, could be altered in the stressed tissues and organs. However, the link between psychological stress and the redox homeostasis or the expression of HSP70 in masseter muscles in rats has not been examined. Therefore, we used a communication box paradigm to induce psychological stress in rats. The successful establishment of the animal model was evidenced by an increase in plasma corticosterone and adrenocorticotropic hormone (ACTH). Meanwhile, the stressed rats showed a decrease in the number of entries on open arms, percentage of time spent in open arms, and distance moved in the elevated plus-maze test. The stressed rats also displayed a decrease in the time spent in the center zone, active velocity, and the distance moved in the open-field test. These results demonstrate affective-like behavioral changes in the stressed rats. Moreover, compared with the control rats, a decrease in SOD, GSH-Px and catalase activities and an increase in MDA content were observed in the masseter muscles in stressed rats after 3 weeks and 5 weeks, and the HSP70 expression was elevated in muscles in the rats exposed to stress for 5 weeks. These results indicate that psychological stress induces oxidative damage and up-regulates the expression of HSP70 in masseter muscles in rats, which are associated with behavior resembling anxiety.     

Social stress in male mice impairs long-term antiviral immunity selectively in wounded subjects

An important property of the antiviral immune response is its time-dependent character. Beginning with a few antigen-specific cells upon infection, it evolves to a stage where there is an abundance of antigen-specific cells and antibodies that are needed to clear the pathogen, and ends with circulating antibodies and a population of virus-specific memory cells to protect the animal from reinfection. Short-term effects of stress on the immune system have been investigated extensively, showing that stress acutely changes many aspects of immunity. However, relatively little is known about the consequences of stress for the quality and quantity of long-term immunological memory. In the present study, we have investigated the effect of social stress, applied in mice at Days 1, 2 and 3 after inoculation with a herpes virus, on long-term antibody and memory cytokine responses to the virus. Male mice were subjected to three 5-min confrontations with an aggressive conspecific. Approximately half of the mice was wounded by bites of the aggressor during this stress procedure, and these mice were analyzed separately from nonwounded mice. It appeared that wounded mice showed suppressed protective antibody responses and impaired memory for virus-specific IL-4 and IL-10 production, whereas mice that were not wounded showed intact long-term immune responses and memory. It is concluded that the combination of wounds and the social stress of repeated confrontations is associated with impaired protective immunity as a consequence of suppressed antibody levels and impairment of some aspects of antiviral immunological memory.     

女性经前期复发性阿弗他溃疡患者血清IL-6、IL-8、TNF-α和sICAM-1的含量变化及其意义

目的:研究女性经前期复发性阿弗他溃疡(经前期RAU)患者血清中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和可溶性细胞间粘附分子-1(sICAM-1)的变化状况, 并探讨经前期RAU的发病机制。方法:用酶联免疫吸附双抗体夹心法(ELISA)检测女性经前期RAU患者外周血中IL-6、IL-8、TNF-α、sICAM-1的水平, 与正常对照组和无经前发作规律的女性RAU对照组相比。结果:经前期RAU患者的血清IL-6、IL-8、TNF-α水平不仅显著高于正常对照组(P＜0.01), 而且高于女性RAU对照组(P＜0.01)。而sICAM-1无明显变化。女性RAU患者血清中TNF-α亦高于正常对照组(P＜0.05)。结论:经前期RAU患者体内存在IL-6、IL-8、TNF-α介导的免疫功能异常, 可能对RAU局部损害起作用。     

Oxidative stress is associated with atopic indices in relation to childhood rhinitis and asthma

BackgroundThe association between oxidative stress and atopic diseases is uncertain. Several risk factors for atopic diseases have been identified, however, a comprehensive investigation of the relationship between oxidative stress markers and atopic indices related to atopic diseases is currently lacking.MethodsWe investigated 132 children who completed a 7-years follow-up in a birth cohort. Oxidative stress markers including plasma glutathione peroxidase (GPx), myeloperoxidase (MPO), total anti-oxidant capacity (TAC), and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured. Allergen-specific IgE levels, FeNO levels, and pulmonary function tests were also obtained.ResultsThe activity of GPx and levels of MPO were inversely correlated to food (shrimp and crab) and house dust mite sensitization respectively. The 8-OHdG levels were strongly negatively correlated with FeNO levels (p < 0.01). A significant positive correlation was found between TAC levels and pre-and post-bronchodilator FVC % and FEV1% predicted (p < 0.05). All oxidative stress markers were not associated with the risk of atopic diseases. However, GPx-related crab sensitization and 8-OHdG related FeNO levels were significantly associated with increased risk of allergic rhinitis, while MPO-related mite sensitization and TAC-related pulmonary function parameters were strongly associated with risk of asthma (p < 0.01).ConclusionOxidative stress is strongly correlated with allergic indices, potentially playing a role in the modulation of allergic responses contributing to atopic diseases.     

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During thelast decade, global consumption grew more than 4-fold. However, molecular mechanismselicited by morphine are not totally understood. Thus, a growing literature indicatesthat there are additional actions to the analgesic effect. Previous studies aboutmorphine and oxidative stress are controversial and used concentrations outside therange of clinical practice. Therefore, in this study, we hypothesized that atherapeutic concentration of morphine (1 μM) would show a protective effect in atraditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogenperoxide (H₂O₂) and/or morphine for 24 h and evaluated cellviability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of theredox state of the cell). Morphine did not prevent the decrease in cell viabilityprovoked by H₂O₂ but partially prevented lipid peroxidationcaused by 0.0025% H₂O₂ (a concentration allowing more than 90%cell viability). Interestingly, this opioid did not alter the increased levels ofsulfhydryl groups produced by exposure to 0.0025% H₂O₂, openingthe possibility that alternative molecular mechanisms (a direct scavenging activityor the inhibition of NAPDH oxidase) may explain the protective effect registered inthe lipid peroxidation assay. Our results demonstrate, for the first time, thatmorphine in usual analgesic doses may contribute to minimizing oxidative stress incells of glial origin. This study supports the importance of employing concentrationssimilar to those used in clinical practice for a better approximation betweenexperimental models and the clinical setting.