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101.
102.
Chaoming Liu Song Liu Lijiao Xiong Limei Zhang Xiao Li Xingling Cao Jinhua Xue Liangdong Li Cheng Huang Zhihua Huang 《International journal of biological sciences》2021,17(4):1088
Microglial M1 depolarization mediated prolonged inflammation contributing to brain injury in ischemic stroke. Our previous study revealed that Genistein-3′-sodium sulfonate (GSS) exerted neuroprotective effects in ischemic stroke. This study aimed to explore whether GSS protected against brain injury in ischemic stroke by regulating microglial M1 depolarization and its underlying mechanisms. We established transient middle cerebral artery occlusion and reperfusion (tMCAO) model in rats and used lipopolysaccharide (LPS)-stimulated BV2 microglial cells as in vitro model. Our results showed that GSS treatment significantly reduced the brain infarcted volume and improved the neurological function in tMCAO rats. Meanwhile, GSS treatment also dramatically reduced microglia M1 depolarization and IL-1β level, reversed α7nAChR expression, and inhibited the activation of NF-κB signaling in the ischemic penumbra brain regions. These effects of GSS were further verified in LPS-induced M1 depolarization of BV2 cells. Furthermore, pretreatment of α7nAChR inhibitor (α-BTX) significantly restrained the neuroprotective effect of GSS treatment in tMCAO rats. α-BTX also blunted the regulating effects of GSS on neuroinflammation, M1 depolarization and NF-κB signaling activation. This study demonstrates that GSS protects against brain injury in ischemic stroke by reducing microglia M1 depolarization to suppress neuroinflammation in peri-infarcted brain regions through upregulating α7nAChR and thereby inhibition of NF-κB signaling. Our findings uncover a potential molecular mechanism for GSS treatment in ischemic stroke. 相似文献
103.
Senwen Feng Junhao Liu Li Hailiang Jianfan Wen Yujun Zhao Xiaofeng Li Guankun Lu Peng Gao Xiancheng Zeng 《Translational oncology》2021,14(8)
Liver cancer was reported to be the sixth most frequently diagnosed cancer, and hepatocellular carcinoma (HCC) accounts for 75%-85% of primary liver cancer. Nevertheless, the concrete molecular mechanisms of HCC progression remain obscure, which is essential to elucidate. The expression profile of RAD54B in HCC was measured using qPCR and western blotting. Moreover, the levels of RAD54B in paraffin-embedded samples were evaluated using immunohistochemistry (IHC). The effect of RAD54B on HCC progression was testified by in vitro experiments, and in vivo orthotopic xenograft tumor experiments. The mechanisms of RAD54B promoting HCC progression were investigated through molecular and function experiments. Herein, RAD54B are dramatically upregulated in HCC tissues and cell lines both on mRNA and protein levels, and RAD54B can servers as an independent prognostic parameter of 5-year overall survival and 5-year disease-free survival for patients with HCC. Moreover, up-regulation of RAD54B dramatically increases the capacity for in vitro cell viability and motility, and in vivo intrahepatic metastasis of HCC cells. Mechanistically, RAD54B promotes the HCC progression through modulating the wnt/β-catenin signaling. Notably, blocking the wnt/β-catenin signaling axis can counteract the activating effects of RAD54B on motility of HCC cells. Besides, further analysis illustrates that DNA amplification is one of the mechanisms leading to mRNA overexpression of RAD54B in HCC. Our findings indicate that RAD54B might be a promising potential prognostic marker and a candidate therapeutic target to therapy HCC. 相似文献
104.
105.
RGMb/DRAGON为RGM家族成员之一,在许多组织和器官中存在并表达.最初它作为粘附分子在神经系统中调节轴突排斥被发现.近来研究发现,它还是BMP的辅助受体,与BMP配体和受体结合,通过调控BMP信号通路在繁殖、肾脏机能的维持以及免疫疾病等生理和病理条件下发挥重要作用.本文评述了RGMb的基因及蛋白结构特征、表达定位及其在神经系统中的作用,并重点介绍了其在BMP信号通路中的作用机制和生物学研究进展. 相似文献
106.
Phytochromes are plant photoreceptors that perceive red and far-red light. Upon the perception of light in Arabidopsis, light-activated phytochromes enter the nucleus and act on a set of interacting proteins, modulating their activities and thereby altering the expression levels of ~10% of the organism’s entire gene complement. Phytochromeinteracting factors (PIFs) belonging to Arabidopsis basic helix-loop-helix (bHLH) subgroup 15 are key interacting proteins that play negative roles in light responses. Their activities are post-translationally countered by light-activated phytochromes, which promote the degradation of PIFs and directly or indirectly inhibit their binding to DNA. The PIFs share a high degree of similarity, but examinations of pif single and multiple mutants have indicated that they have shared and distinct functions in various developmental and physiological processes. These are believed to stem from differences in both intrinsic protein properties and their gene expression patterns. In an effort to clarify the basis of these shared and distinct functions, we compared recently published genome-wide ChIP data, developmental gene expression maps, and responses to various stimuli for the various PIFs. Based on our observations, we propose that the biological roles of PIFs stem from their shared and distinct DNA binding targets and specific gene expression patterns. 相似文献
107.
Alexander G. Cheroske Thomas W. Cronin Mary F. Durham Roy L. Caldwell 《Marine and Freshwater Behaviour and Physiology》2013,45(4):219-232
Stomatopod crustaceans (mantis shrimp) are aggressive benthic marine predators with extraordinary color vision. When communicating with conspecifics, many stomatopods display conspicuously colored body areas, often in combination with other types of signals such as motion and chemical cues. Some species occupy wide depth ranges (>30 m), where changing light conditions can influence color perception. To test the potential effects of differing ambient lights on signaling behavior, stomatopods (Gonodactylus smithii) interacted with conspecifics in aquaria, under full-spectrum, high intensity light or light restricted in either spectrum or intensity. During intrasexual and intersexual trials in full-spectrum, high intensity light, animals performed more aggressive acts using colored body parts (meral spread, lunge, strike). Stomatopods used significantly more antennular flicking, and performed aggressive acts at reduced distances under restricted light conditions. To compare the use of antennules in visual and chemical communication, additional experiments showed more antennular flicking in response to chemical stimuli from food or conspecifics compared to seawater controls. This response ceased immediately after ablation of antennular chemoreceptors but returned to pre-treatment levels after 5 days of recovery. These findings suggest that stomatopods can vary their use of signals during conspecific interactions under different photic conditions. These inducible, plastic behavioral responses can potentially improve signal transfer in varying light environments. 相似文献
108.
Antonio Díaz-Cruz Raquel Guinzberg Ruy Guerra Magdalena Vilchis Daniel Carrasco Francisco J. García-vázquez 《Free radical research》2013,47(6):663-672
It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose. These membranes showed catalytic activity of Nox isoforms, probably Nox 2 based on its complete inhibition with specific antibodies. NADPH was oxidized to convert O2 into superoxide radical, later transformed into H2O2. This enzymatic activity requires previous activation with either 3 mM Mn2+ or guanosine 5′-0-(3-thiotriphosphate) (GTPγS) plus adrenaline. Experimental conditions for activation and catalytic steps were set up: ATP was not required; S0.5 for NADPH was 44 μM; S0.5 for FAD was 8 μM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was inhibitory. Activation with GTPγS plus adrenaline was dose- and Ca2+-dependent and proceeded through α1-adrenergic receptors (AR), whereas β-AR stimulation resulted in inhibition of Nox activity. These results lead us to propose H2O2 as additional transduction signal for adrenaline response in hepatic cells. 相似文献
109.
《Free radical research》2013,47(5):422-431
AbstractHomocysteine (Hcy) at elevated levels is a putative risk factor for many cardiovascular disorders including atherosclerosis. In the present study, we investigated the effect of Hcy on the expression of cyclooxygenase (COX)-2 in murine macrophages and the mechanisms involved. Hcy increased the expression of COX-2 mRNA and protein in dose- and time-dependent manners, but did not affect COX-1 expression. Hcy-induced COX-2 expression was attenuated not only by the calcium chelators, EGTA and BAPTA-AM, but also by an antioxidant, N-acetylcysteine. Calcium chelators also attenuated Hcy-induced reactive oxygen species (ROS) production in macrophages, indicating that Hcy-induced COX-2 expression might be mediated through ROS generated by calcium-dependent signaling pathways. In another series of experiments, Hcy increased the intracellular concentration of calcium in a dose-dependent manner, which was attenuated by MK-801, an N-methyl-D-aspartate (NMDA) receptor inhibitor, but not by bicuculline, a gamma-aminobutyric acid receptor inhibitor. Molecular inhibition of NMDA receptor using small interfering RNA also attenuated Hcy-induced increases in intracellular calcium. Furthermore, both ROS production and Hcy-induced COX-2 expression were also inhibited by MK-801 as well as by molecular inhibition of NMDA receptor. Taken together, these findings suggest that Hcy enhances COX-2 expression in murine macrophages by ROS generated via NMDA receptor-mediated calcium signaling pathways. 相似文献
110.
《Free radical research》2013,47(9):1085-1094
AbstractMitochondrial superoxide flash (mitoflash) reflects quantal and bursting superoxide production and concurrent membrane depolarization triggered by transient mitochondrial permeability transition in many types of cells, at the level of single mitochondria. Here we investigate reactive oxygen species (ROS)-mediated modulation of mitoflash activity in cardiac myocytes and report a surprising finding that hypochlorite ions potently and preferentially triggered mitoflashes in the subsarcolemmal mitochondria (SSM), whereas hydrogen peroxide (H2O2) elicited mitoflash activity uniformly among SSM and interfibrillar mitochondria (IFM). The striking SSM mitoflash response to hypochlorite stimulation remained intact in cardiac myocytes from NOX2-deficient mice, excluding local NOX2-mediated ROS as the major player. Furthermore, it occurred concomitantly with SSM Ca2+ accumulation and local Ca2+ and CaMKII signaling played an important modulatory role by altering frequency and unitary properties of SSM mitoflashes. These findings underscore the functional heterogeneity of SSM and IFM and the oxidant-specific responsiveness of mitochondria to ROS, and may bear important ramifications in devising therapeutic strategies for the treatment of oxidative stress-related heart diseases. 相似文献