脑出血继发损伤中沉默信息调节因子2的表达和炎症反应*

目的：探讨脑出血对酵母沉默信息调节因子2（Sirt2）和炎症的影响。方法：将胶原酶Ⅳ注入SD大鼠右侧 纹状体中建立脑出血模型，通过免疫印迹和ELISA 等方法测定大鼠脑出血后48 h 的Sirt2 的表达及炎症变化。利 用Hemin 诱导PC12 细胞损伤模拟体外脑出血模型，并检测Sirt2 及炎症变化；采用短发夹RNA（shRNA）-Sirt2 沉 默Sirt2 在PC12 细胞中的表达及对炎症的影响。结果：手术后48 h 脑出血行为学评分最低。脑出血组Sirt2 的表达 显著高于假手术组。脑出血组IL-6、IL-1β 表达显著升高。结论：脑出血可以促进Sirt2 的表达和炎症反应，降低 Sirt2 的表达可减缓炎症反应。 关键词 脑出血；沉默信息调节     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。     

Cdk13表达对神经元轴突伸长的影响

目的探讨智力障碍相关基因Cdk13对神经轴突伸长的影响。方法通过基因敲除模型、质粒细胞转染等方法,荧光共聚焦显微镜成像技术检测神经元轴突的形态,观察轴突伸长的变化。结果 Cdk12和Cdk13在神经系统中有表达,在敲除Cdk12和Cdk13后轴突长度比对照组减少,两者比较有统计学差异(P0.05),敲除Cdk12和Cdk13基因后Cdk5 mRNA水平降低。结论 Cdk13和Cdk12的表达对神经元轴突的生长至关重要,其失活会引起神经元轴突形态异常,可能是导致智力障碍的病理机制。     

Deoxynivalenol induces apoptosis in PC12 cells via the mitochondrial pathway

Deoxynivalenol (DON) has broad toxicity in animals and humans. In this study the impact of DON treatment on apoptotic pathways in PC12 cells was determined. The effects of DON were evaluated on (i) typical indicators of apoptosis, including cellular morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio in PC12 cells, and on (ii) the expression of key genes and proteins related to apoptosis, including Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3. DON treatment inhibited proliferation of PC12 cells, induced significant morphological changes and apoptosis, promoted the release of Cyt C and AIF from the mitochondria, and increased the activities of cleaved-Caspase9 and cleaved-Caspase3. Bcl-2 expression decreased with increasing DON concentrations, in contrast to Bax and Bid, which were increased with increasing DON concentration. These data demonstrate that DON induces apoptosis in PC12 cells through the mitochondrial apoptosis pathway.     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Changes in the SF-12 among Depressed Elders Six Months after Discharge from an Inpatient Geropsychiatric Unit

Using the SF-12 to measure physical and mental functioning, the authors examine the intra-individual changes in health-related quality of life (HRQOL) 6 months post-discharge for depressed older adults. In addition, they examine three sets of predictors that might influence these changes. The sample of depressed older adults was recruited from an inpatient geropsychiatry unit. Although their physical and mental health scores on the SF-12 were lower than comparable norms, the sample showed an average increase in their mental functioning but a decrease in the physical functioning over the 6 months. Negative life-events were significant predictors of people who reported no change in their mental health functioning and decreases in their physical health functioning. Interestingly, those who experienced positive life events were more likely to report declines and younger participants were more likely to report no change in their physical functioning. The findings indicate that the effects of depression on HRQOL can have enduring effects on a sample of previously hospitalized older adults. The significance of life event changes might signify the importance of taking into account non-traditional areas of medical interventions. Further, the findings indicate the usefulness of the SF-12 quantifying HRQOL outcomes.     

Leber’s hereditary optic neuropathy and vitamin B12 deficiency

Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON.Methods A case series was observed.Results Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal vitamin B12 serum level at the time of presentation.Conclusions The clinical picture of optic neuropathy associated with vitamin B12 deficiency shows similarity to that of LHON. Both involve the nerve fibres of the papillomacular bundle. The present case reports suggest that optic neuropathy in patients carrying a primary LHON mtDNA mutation may be precipitated by vitamin B12 deficiency. Therefore, known carriers should take care to have an adequate dietary intake of vitamin B12 and malabsorption syndromes like those occurring in familial pernicious anaemia or after gastric surgery should be excluded.