整合应激反应在中枢神经系统疾病中的研究进展

整合应激反应是真核细胞受到细胞内外刺激后产生的适应性反应。整合应激反应激活后会抑制大部分蛋白的翻译,但会促进某些特定蛋白的翻译,以应对复杂的细胞微环境变化。大量研究发现,在多种神经系统疾病中,整合应激反应可以被疾病相关细胞应激信号所激活,并通过学习和记忆巩固、髓鞘再生、突触可塑性等过程参与疾病的发生与发展。本文总结了整合应激反应在中枢神经系统疾病中的作用、机制和可能的药物靶点,探讨了药理学手段调节整合应激反应在治疗中枢神经系统疾病的潜力,以期能够对中枢神经系统疾病的病理研究和药物开发提供参考。

浅谈短跑中的心理训练

随着竞技运动的不断发展,姑且不论短跑运动员天赋的差异,就其技术水平而言,差距在逐渐缩小。但比赛场上的胜利除了运动员的天赋使然,也有后天不懈训练的毅力锤炼,当然其中更离不开运动员稳定的心理素质。在某些时候,心理素质的高低决胜甚至会超越竞技技术在比赛中的作用。因此,笔者认为,运动员的心理训练是确有必要,它可以增强运动员在竞技中的信心,以更完美的状态进入比赛。本文就心理训练在短跑运动中的重要功能及技巧运用浅析论之。

γ-氨基丁酸的生理作用及应用

γ-氨基丁酸(gamma-aminobutyric acid ,GABA)是生物应激反应体系的重要氨基酸,广泛分布于自然界中。长久的进化使得生物可以通过GABA的H +和Ca 2+依赖方式响应于内外界应激。可以通过腐胺途径和GABA分流途径干涉生物内能量代谢、碳氮代谢的方式缓解生物体内压力。GABA在生物体内组织发育和形成、生物内和生物间的信号交流中扮演着重要角色。作为癫痫等疾病的特效药,可降解尼龙的前体物质GABA有着长足的发展空间。分析了GABA的生理机制,综述了谷氨酸脱羧酶及其基因定点突变的研究,最后对GABA的制备方法与应用进行了介绍。

吐法的机制和应用探讨

对吐法的特点进行分析,认为从祛邪或攻邪来认识吐法的作用机制有局限性,应注意吐法与中医气机调节的关系,并从现代反射理论和应激反应调节理论来深入探讨吐法的作用机制,说明吐法的特长是治疗急症和慢性顽固性疾病,但其应用范围可以被拓展。

Astragalus mongholicus polysaccharide inhibits lipopolysaccharide-induced production of TNF-α and interleukin-8

AIM： To explore the effect of Astraga/us mongholicus polysaccharide （APS） on gene expression and mitogenactivated protein kinase （MAPK） transcriptional activity in intestinal epithelial cells （IEC）. METHODS： IEC were divided into control group, lipopolysaccharide （LPS） group, LPS＋ 50 μg/mL APS group, LPS＋ 100 μg/mL APS group, LPS＋ 200 μg/mL APS group, and LPS＋ 500 μg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor （TNF）-α and interleukin （IL）-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS： The levels of TNF-α and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-α and IL-8 genes. APS did not block the activation of extracellular signal- regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-α and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway.CONCLUSION： APS-modulated bacterial productmediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation.

p28^GANK inhibits endoplasmic reticulum stress-induced cell death via enhancement of the endoplasmic reticulum adaptive capacity

It has been shown that oncoprotein p28GANK, which is consistently overexpressed in human hepatocellular carcinoma （HCC）, plays a critical role in tumorigenesis of HCC. However, the underlying mechanism remains unclear. Here, we demonstrated that p28GANK inhibits apoptosis in HCC cells induced by the endoplasmic reticulum （ER） stress. During ER stress, p28GANK enhances the unfolded protein response, promotes ER recovery from translational repression, and thereby facilitates cell＇s ability to cope with the stress conditions. Furthermore, p28GANK upregulates glucose-regulated protein 78 （GRP78）, a key ER chaperone protein, which subsequently enhances the ER folding capacity and promotes recovery from ER stress. We also demonstrated that p28GANK increases p38 mitogen-activated protein kinase and Akt phosphorylation, and inhibits nuclear factor kappa B （NF-κB） activation under ER stress, which in turn contributes to GRP78 upregulation. Taken together, our results indicate that p28GANK inhibits ER stress-induced apoptosis in HCC cells, at least in part, by enhancing the adaptive response and GRP78 expression. We propose that p28GANK has potential implications for HCC progression under the ER stress conditions.

单增李斯特菌DegU直接调控CtsR介导的温度适应

在食品加工过程中温和的热处理方式难以完全消灭耐热性强的食源性单增李斯特菌,该菌对食品安全构成显著风险。团队前期发现李斯特菌孤儿反应调节因子DegU与细菌的耐热应激密切相关,为进一步探索DegU参与温度适应调控的分子机制,本研究以单增李斯特菌EGD-e为参考菌株,利用同源重组方法构建单增李斯特菌基因缺失株ΔdegU和回补株CΔdegU,在前期基础上挖掘DegU调控单增李斯特菌适应环境温度的相关分子机制。研究结果显示:荧光定量PCR试验发现单增李斯特菌缺失degU后导致基因ctsR(编码应激调节因子CtsR)的转录水平显著降低;凝胶迁移阻滞试验首次证明DegU能与基因ctsR的启动子区结合,表明DegU以直接方式调控ctsR。综上,本研究发现DegU通过直接调控应激调节因子CtsR的表达适应环境温度变化,为进一步深入理解单增李斯特菌等重要人兽共患病原菌适应环境应激过程中的调控机制奠定了研究基础,具有重要的公共卫生学意义。

Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats

Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.

提高老年人着装品质的几个关键词

当今社会老龄化程度在进一步加深。由于老年人须发容貌、皮肤、身高体重等外表会发生退行性改变，感官及内脏器官新陈代谢功能会下降，视、听、嗅、触觉及应激调节反应会减退，记忆力和认知功能会减弱乃至格性上会发生变化，因此关爱老年人，并在衣、食、住、行、养、乐、医等方面不断提高老年人生活品质就显得特别重要。本文仅从服装专业视角出发，结合老年人特有的生理及心理变化，谈一些提高老年人着装品质的看法。

The inhibitory activities of Urtica fissa to BPH

In the present study, the BPH inhibitory activities of Urtica fissa were systematically investigated. Firstly, inhibitory activities of 5α reductase of the alcoholic extracts from different parts(root, stem, leaf, flower and fruit) were evaluated. The results indicated that the root possessed the most significant action. Subsequently, U. fissa root(UFR) was subjected to further pharmacological evaluation using the benign prostate hyperplasia(BPH) model rats induced by testosterone propionate. The results revealed that UFR could significantly decrease the prostate index, alter the hyperplasia tissue morphology, suppress the prostatic growth factors of VEGF, EGF, bF GF and KGF, decrease the inflammation factor levels of TNF-α, IL-1β and IL-6, improve the activities of GSH-Px, CAT and SOD and decrease the MDA level in the prostate of the model rats. Moreover, UFR also significantly suppressed the hormone levels of testosterone and dihydrotestosterone. These results indicated that the possible BPH inhibitory mechanisms of UFR were growth factor suppression, hormone level modulation, anti-inflammation, and anti-oxidative stress.

Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in the hippocampi of perimenopausal rats induced by immobilization stress

OBJECTIVE: We wished to study the impact of Chaihushugan San(CSS) on the behavior of perimenopausal rats with liver-Qi stagnation(LQS) and to investigate the effect of CSS on signal transduction of the Raf/mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK) cascade in the hippocampi of rats induced by immobilization.METHODS: Twenty 52-week-old female rats were divided into two groups by the random number table method: model control group(MCG) and CSS group(CSSG), with 10 rats in each group.Ten-week-old female rats were used as the normal control group(NCG). CSS effects were assessed using rats exposed to immobilization stress by measuring body weight and sucrose consumption, serum hormone levels, and observing performance in the open field test(OFT). Molecular mechanisms were examined by measuring the effect of CSS on expression of Raf1, MEK1/2 and ERK1/2 m RNA in hippocampi using quantitative real-time polymerase chain reaction and by measuring levels of these proteins and related phospho-proteins using Western blotting.RESULTS: Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose consumption; and increased serum levels of corticotropin releasing hormone(CRH) and corticosterone(CORT). Activation of hippocampal Raf/MEK/ERK cascade was suppressed significantly in the MCG,and activation was increased after 21 days of CSS treatment.CONCLUSION: CSS has significant effects upon relief of the symptoms of LQS in immobilization-induced rats. The mechanism underlying this action might(at least in part) be mediated by reversal of disruption of the Raf/MEK/ERK pathway.