2,606 research outputs found

    P-coumaric acid reverses depression-like behavior and memory deficit via inhibiting AGE-RAGE-Mediated neuroinflammation

    Get PDF
    Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1β and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression

    Scientific layout and integrative development of urban and rural health and family planning resources under the background of the new urbanization

    Get PDF
    新型城镇化是中国现代化的必由之路,是扩大内需、促进区域协调发展的重要抓手。新型城镇化建设客观上要求城乡卫生计生资源配置逐步破除城乡二元体制,科学布局,均衡发展。基于当前S省城乡卫生计生资源在整合方面的滞后性、配置方面的非均衡性、布局与发展方面的不适应性等问题,以及对S省城乡卫生计生资源整合的挑战与机遇分析,本研究提出在新型城镇化进程中应该正确认识城乡卫生计生资源整合的必要性和发展的持续性,厘清整合后卫生和计生部门之间的关系,实现S省城乡卫生计生资源科学布局与融合发展,保障城乡居民的医疗卫生服务需求,推进新型城镇化建设的质量和速度。New type of urbanization is the only way for China's modernization and the key to expanding domestic demand and promoting regional coordinated development. The new urbanization objectively requires the urban and rural health planning resources to gradually get rid of the urban-rural dual structure, scientific layout, balanced development. Based on the hysteretic integration, imbalance allocation, and the analysis of health family and planning resources integration between urban and rural areas in our province, this paper argues that in the new urbanization, we should correctly understand the necessity of health and family planning resources integration and the  sustainability of development. In addition, it is very important to clarify the relationship between health and family planning department after integration. Only in this way, our province can realize the scientific layout and integrative development of urban and rural health and family planning resources, ensure the health service demand of urban and rural residents, and promote the quality and speed of the new type of urbanization construction

    滨螺卓越的耐高温能力,温度耐受上限竟高达55℃——潮间带 Echinolittorina 属滨螺细胞质苹果酸脱氢酶高温耐受机制的研究

    Get PDF
    研究团队以分布于高潮间带,具有高耐热性的两种滨螺为研究对象,通过生理生化学实验及计算机模拟手段,发现耐热的软体动物通过增强代谢关键酶的作用,避免了在高温条件下的解链;研究团队还提出,局部柔性的增长使得酶在低温条件下能够发挥其催化功能,同时能在极端高温条件下,起到稳定蛋白质的作用,确保了蛋白质功能的维持。这些发现对于查明环境温度对生物分布的影响及其机制,预测气候变暖的生态学效应将具有重要意义。 滨螺广泛分布于潮间带高潮区,是潮间带垂直分布区划分的标志性物种。塔结节滨螺(Echinolittorina malaccana)和粒结节滨螺(E. radiata)是我国岩相潮间带高潮区常见物种,其温度耐受上限高达 55-60°C。董云伟教授团队与美国斯坦福大学 George Somero 教授,以及华侨大学张光亚教授团队合作,进行了一系列研究,探索了高热耐受性滨螺在极端高温条件下,仍旧保持体内蛋白质微结构的完整、功能的维持的奥妙所在。【Abstract】Snails of the genus Echinolittorina are among the most heat-tolerant animals; they experience average body temperatures near 41–44℃ in summer and withstand temperatures up to at least 55℃. Here, we demonstrate that heat stability of function (indexed by the Michaelis–Menten constant of the cofactor NADH, KMNADH) and structure (indexed by rate of denaturation) of cytosolic malate dehydrogenases (cMDHs) of two congeners (E. malaccana and E. radiata) exceeds values previously found for orthologs of this protein from less thermophilic species. The ortholog of E. malaccana is more heat stable than that of E. radiata, in keeping with the congeners' thermal environments. Only two inter-congener differences in amino acid sequence in these 332 residue proteins were identified. In both cases (positions 48 and 114), a glycine in the E. malaccana ortholog is replaced by a serine in the E. radiata protein. To explore the relationship between structure and function and to characterize how amino acid substitutions alter stability of different regions of the enzyme, we used molecular dynamics simulation methods. These computational methods allow determination of thermal effects on fine-scale movements of protein components, for example, by estimating the root mean square deviation in atom position over time and the root mean square fluctuation for individual residues. The minor changes in amino acid sequence favor temperature-adaptive change in flexibility of regions in and around the active sites. Interspecific differences in effects of temperature on fine-scale protein movements are consistent with the differences in thermal effects on binding and rates of heat denaturation.This research was substantially supported by grants from National Natural Science Foundation of China (41476115), Program for New Century Excellent Talents of Ministry of Education, China, Nature Science Foundation for Distinguished Young Scholars of Fujian Province (2017J07003), China and the State Key Laboratory of Marine Environmental Science Internal Program, Xiamen University (MELRI1501)

    The role of spinal GABAB receptors in cancer-induced bone pain in rats

    Get PDF
    Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats. Our behavioral results show that both acute and chronic intrathecal treatment with baclofen, a GABABR agonist, significantly attenuated CIBP-induced mechanical allodynia and ambulatory pain. The expression levels of GABABRs were significantly decreased in a time-dependent manner and colocalized mostly with neuron and a minority with astrocyte and microglia. Chronic treatment with baclofen restored the expression of GABABRs and markedly inhibited the activation of cAMP-dependent protein kinase (PKA) and the cAMP-response element-binding protein (CREB) signaling pathway

    Developmental changes in the role of different metalinguistic awareness skills in Chinese reading acquisition from preschool to third grade

    Get PDF
    Copyright @ 2014 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The present study investigated the relationship between Chinese reading skills and metalinguistic awareness skills such as phonological, morphological, and orthographic awareness for 101 Preschool, 94 Grade-1, 98 Grade-2, and 98 Grade-3 children from two primary schools in Mainland China. The aim of the study was to examine how each of these metalinguistic awareness skills would exert their influence on the success of reading in Chinese with age. The results showed that all three metalinguistic awareness skills significantly predicted reading success. It further revealed that orthographic awareness played a dominant role in the early stages of reading acquisition, and its influence decreased with age, while the opposite was true for the contribution of morphological awareness. The results were in stark contrast with studies in English, where phonological awareness is typically shown as the single most potent metalinguistic awareness factor in literacy acquisition. In order to account for the current data, a three-stage model of reading acquisition in Chinese is discussed.National Natural Science Foundation of China and Knowledge Innovation Program of the Chinese Academy of Sciences
    corecore