Effect of dexamethasone on nitric oxide synthase and Caspase-3 gene expressions in endotoxemia in neonate rat brain

INTRODUCTION Fifty percent to seventy percent of the patientsare complicated with brain damage at various degreesduring endotoxemia, which is characterized bydamage to the neurons, microvascular injury,increased endothelial permeability, and neutrophilinfiltration and accumulation in the brain. It has beenrecognized that bacterial endotoxin (lipopolysaccharideLPS) plays important roles in this pathophysiologicalprocess, but the mechanism and approach toprevention of brain damage during en…     

Potential association of lead exposure during early development of mice with alteration of hippocampus nitric oxide levels and learning memory

Objective Chronic lead （Pb） exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains. Methods Sixty Balb/c mice aged l0 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05% 0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay. Results Compared with control groups, （1） the weight of 0.075% group was significantly reduced （P〈0.05）; （2） The number of times in mice attaining the required standards in T-water maze test was lower in 0.075% group （P〈0.01）. No significant difference was found between experimental and control groups in open field test （P〉0.05）; （3） NO level of mouse hippocampus tissue was decreased in 0.075% group （P〈0.01）. Conclusions The findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.     

Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems

Background

Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats.

The association between inflammatory markers (iNOS,HO-1, IL-33, MIP-1β) and depression with and without posttraumatic stress disorder

Background

Both major depression and posttraumatic stress disorder (PTSD) are characterized by inflammation, increased concentration levels of proinflammatory cytokines, decreased neurogenesis followed by neuroprogression, as well as mitochondrial and the hypothalamic-pituitary-adrenal axis dysfunction. Elevated levels of oxidative stress caused by an increased activity of prooxidants over antioxidants are also observed. Based on several reports, depressive episodes can lead to the sensitization of immune-inflammatory pathways. Thus, depression, PTSD, and depression comorbid with PTSD are associated with immune-inflammatory markers. The study aimed at evaluating concentration levels of iNOS, HO-1, IL-33, and MIP-1β in depression with and without PTSD.

Short-term inhalation study of graphene oxide nanoplates

Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague–Dawley rats. A total of four groups (15 rats per group) were exposed: (1) control (fresh air), (2) low concentration (0.76?±?0.16?mg/m³), (3) moderate concentration (2.60?±?0.19?mg/m³), and (4) high concentration (9.78?±?0.29?mg/m³). The rats were exposed to graphene oxide for 6?h/day for 5 days, followed by recovery for 1, 3, and 21 days. No significant body or organ weight changes were noted after the short-term exposure or during the recovery period. Similarly, no significant systemic effects of toxicological importance were noted in the hematological assays, bronchoalveolar lavage fluid (BAL) inflammatory markers, BAL fluid cytokines, or blood biochemical assays following the graphene oxide exposure or during the post-exposure observation period. Moreover, no significant differences were observed in the BAL cell differentials, such as lymphocytes, macrophages, or polymorphonuclear cells. Graphene oxide-ingested alveolar macrophages as a spontaneous clearance reaction were observed in the lungs of all the concentration groups from post 1?day to post 21 days. Histopathological examination of the liver and kidneys did not reveal any significant test-article-relevant histopathological lesions. Importantly, similar to previously reported graphene inhalation data, this short-term nose-only inhalation study found only minimal or unnoticeable graphene oxide toxicity in the lungs and other organs.     

Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions

To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH₂), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications.     

注射用鼠神经生长因子对急性脑梗死患者血清神经元特异性烯醇化酶和一氧化氮合酶活性的影响

目的 探讨注射用鼠神经生长因子（NGF）对急性脑梗死患者血清神经元特异性烯醇化酶（NSE）和一氧化氮合酶（NOS）活性的影响。方法 选择2015年3月—2017年7月住院治疗的急性脑梗死患者92例,随机分为常规组（n=46）和mNGF组（n=46）。常规组按常规方法给予抗血小板聚集、降颅压、降脂稳定斑块、控制血压血糖、抗感染、维持水电平衡等,根据患者个体情况应用脱水剂及加强营养;mNGF组在常规治疗基础上加用鼠NGF肌肉注射治疗,30 μg/次,1次/d,共治疗28 d。对比两组治疗后总有效率,观察并比较两组治疗前后NIHSS评分、Barthel指数及血清NSE、一氧化氮（NO）、NOS水平。结果 mNGF组治疗后总有效率（89.13%）明显高于常规组（67.39%）,两组治疗后总有效率比较差异有统计学意义（P<0.05）。与治疗前比较,两组治疗28 d后NIHSS评分明显下降（P<0.05）、Barthel指数明显增高,同组治疗前后比较差异均有统计学意义（P<0.05）;但mNGF组变化程度大于常规组,组间差异有统计学意义（P<0.05）。两组治疗前NSE、NO及NOS水平无统计学差异;两组治疗14 d、28 d后NSE、NO及NOS水平明显下降,同组治疗前后比较差异有统计学意义（P<0.05）;但mNGF组下降幅度明显大于常规组,组间差异有统计学意义（P<0.05）。结论 注射用鼠NGF治疗能有效降低急性脑梗死患者血清NSE和NOS活性,从而发挥对缺血脑损伤的保护作用,促进神经功能的恢复。     

Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson's disease is mediated by a reduction of inducible nitric oxide synthase

Objective: Parkinson's disease (PD) is characterized by deterioration of the nigrostriatal system and associated with chronic neuroinflammation. Glial activation has been associated with regulating the survival of dopaminergic neurons and is thought to contribute to PD through the release of proinflammatory and neurotoxic factors, such as reactive nitric oxide (NO) that triggers or exacerbates neurodegeneration in PD. Polyunsaturated fatty acids (PUFAs) exert protective effects, including antiinflammatory, antiapoptotic, and antioxidant activity, and may be promising for delaying or preventing PD by attenuating neuroinflammation and preserving dopaminergic neurons. The present study investigated the effects of fish oil supplementation that was rich in PUFAs on dopaminergic neuron loss, the density of inducible nitric oxide synthase (iNOS)-immunoreactive cells, and microglia and astrocyte reactivity in the substantia nigra pars compacta (SNpc) and striatal dopaminergic fibers.

Methods: The animals were supplemented with fish oil for 50 days and subjected to unilateral intrastriatal 6-hydroxydopamine (6-OHDA)-induced lesions as a model of PD.

Results: Fish oil mitigated the loss of SNpc neurons and nerve terminals in the striatum that was caused by 6-OHDA. This protective effect was associated with reductions of the density of iNOS-immunoreactive cells and microglia and astrocyte reactivity.

Discussion: These results suggest that the antioxidant and antiinflammatory properties of fish oil supplementation are closely related to a decrease in dopaminergic damage that is caused by the 6-OHDA model of PD.     

银杏蜜环口服溶液作用p38 MAPK调节eNOS/NO信号途径保护人脐静脉内皮细胞缺氧复氧损伤

目的:评估银杏蜜环口服溶液对缺氧复氧损伤人脐静脉内皮细胞(HUVECs)的保护作用;从p38丝裂原活化蛋白激酶(p38 MAPK)及内皮型一氧化氮合酶(e NOS)/一氧化氮(NO)信号途径探讨银杏蜜环口服溶液保护受损HUVECs的药效机制。方法:缺氧缺糖/复氧复糖法建立体外HUVECs缺血再灌注损伤模型。分为正常组、模型组、银杏蜜环口服溶液高质量浓度组(75 mg·L-1,简称银蜜高),低质量浓度组(36 mg·L-1,简称银蜜低),p38 MAPK抑制剂SB203580组,银蜜高+SB203580组,e NOS抑制剂亚硝基左旋精氨酸甲酯(L-NAME)组,银蜜高+L-NAME组。细胞增殖-毒性检测试剂盒(CCK-8)及微量酶标法检测细胞活力及细胞损伤;蛋白免疫印迹法(Western blot)检测磷酸化p38 MAPK(p-p38 MAPK)/p38 MAPK和磷酸化e NOS(p-e NOS)/e NOS蛋白表达;酶联免疫吸附法(ELISA)检测肿瘤坏死因子-α(TNF-α),可溶性细胞间黏附分子-1(s ICAM-1),半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)含量;硝酸盐还原酶法检测NO含量。结果:银蜜高、银蜜低组可显著提高缺氧复氧损伤HUVECs活力、降低细胞乳酸脱氢酶(LDH)漏出量(P0.05,P0.01);抑制受损细胞p38的磷酸化(P0.05),降低细胞培养上清中TNF-α,s ICAM-1含量(P0.05,P0.01)。在给予银蜜高或(和)SB203580后,受抑制的e NOS磷酸化表达水平显著升高(P0.05);银蜜高可显著提高受损细胞NO含量,在加入e NOS抑制剂L-NAME后,银蜜高可拮抗L-NAME降低细胞NO生成和升高Caspase-3的作用(P0.05)。结论:银杏蜜环口服溶液可提高氧复氧损伤HUVEs活力,具有抗炎、调节内皮系统、抑制细胞凋亡的作用,机制与其作用于p38 MAPK进而调节e NOS-NO信号途径相关。     

稀土氧化物着色钇稳定四方多晶氧化锆陶瓷与饰面瓷匹配性的研究

目的:探讨通过添加稀土氧化物着色剂而制备的钇稳定四方多晶氧化锆陶瓷与饰面瓷的匹配性。方法:以稀土氧化物(Pr6O11,CeO2,Er2O3)和过渡元素氧化物(MnO2)为着色剂,采用粉体掺杂方法,在四方多晶氧化锆陶瓷粉体中添加不同质量分数的着色剂,制备出6组钇稳定四方多晶氧化锆陶瓷,测定其与Vita VM9饰面瓷的抗热震性能及界面结合强度。采用SAS6.12软件包对数据进行单因素方差分析。结果:6组钇稳定四方多晶氧化锆陶瓷与Vita-VM9饰面瓷烧结后,各组在60℃～240℃测试过程未发现径向或层间开裂或裂纹现象,加热温度>240℃。6组钇稳定四方多晶氧化锆陶瓷与VitaVM9饰面瓷界面的抗剪切强度值为(36.03±3.82)～(37.98±4.89)MPa,均高于纯四方氧化锆陶瓷组的剪切强度值,但各组与纯四方氧化锆陶瓷的抗剪切强度值无显著差异(P>0.05)。结论:稀土氧化物着色钇稳定四方多晶氧化锆陶瓷与饰面瓷的匹配性达到临床应用水平。