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Oxidative stress and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) influence atherosclerosis formation and development. Oxidative stress significantly influences the abnormal proliferation and migration of VSMCs, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a major antioxidant factor. However, the precise function of Nrf2 in the regulation of abnormal proliferation and migration of VSMCs and atherosclerosis is unclear. We investigated the proliferation and migration of VSMCs in atherosclerosis in male Apoe −/− and Apoe −/− Nrf2 −/− mice fed a high-fat diet for 12 weeks. In cultured mouse VSMCs, we studied the effect of Nrf2 on ox-LDL-stimulated proliferation and migration by using siRNA treatment to silence Nrf2. We then performed dual luciferase reporter and immunoprecipitation assays to study the interaction between Nrf2 and the promoter sequence of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Our results demonstrate that Nrf2 expression levels were increased in the aorta and VSMCs of mice in the atherosclerosis model group compared with the control group. We also provide evidence that Nrf2 deficiency attenuated atherosclerotic plaque burden, diminished proliferation, and migration of VSMCs but enhanced VSMC-specific marker gene expression in vitro and in vivo. This is related to Nrf2 binding to the promoter sequence of LOX-1. Furthermore, Nrf2 downregulation contributes to restrain both transcriptional and translational activities of LOX-1. Together, our data indicate that Nrf2 insufficiency is linked to attenuation of atherosclerosis, and could diminish the pathological process by blunting LOX-1-mediated proliferation and migration of VSMCs. [Display omitted] • Nrf2 drives atherosclerotic plaque formation. • Ox-LDL augments the expression of Nrf2 in mouse vascular smooth muscle cells (VSMCs). • Nrf2 induces proliferation and migration of VSMCs in Apoe −/− mice and in vitro. • Nrf2 deficiency diminishes LOX-1 activity and the oxidative stress level of VSMCs in vitro and in vivo. • Nrf2 binds LOX-1 promoter and increases its expression. [ABSTRACT FROM AUTHOR]

Highlights • Mice with remote fear memory are sensitive to original and novel reconditioning. • Reconditioning in an original fearful context causes remote fear memory resistance. • Reconditioning in a novel context produces more fear reactions in mice with remote fear memory. • Stress sensitivity of remote fear may be induced by fear memory system consolidation over time. Abstract Exposure of some individuals to recurring traumatic events from the same perpetrator or situation, such as during child abuse or domestic violence, is quite prevalent. Studies have shown that the number of traumatic events experienced is positively related to the severity of post-traumatic stress disorder and other mental disorders. Using a contextual fear conditioning (Cond1) and reconditioning (Cond2) paradigm, which were separated by either 1 or 35 days, we examined fear responses to immediate extinction and retrieval-extinction procedures after repeated fear conditioning stress. Based on the time interval between Cond1 and Cond2, the animals were divided into recent and remote fear memory groups. We observed that when Cond2 was performed in the original conditioning context in which Cond1 was performed, the reconditioned remote fear memory was resistant to the disruptive effect of immediate extinction and retrieval-extinction paradigms. Furthermore, the resistance to disruptive effects could be induced by very low shock intensities, which cannot even induce any fear response in naive animals. When Cond2 was performed in a novel context, animals with remote fear memory acquired a significantly higher fear response to the novel context. Our findings suggest that remote fear memory may be more sensitive to reconditioning and resistant to post-reconditioning disruption. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported. In this study, we established a photothrombotic mouse PSCI model and showed that after EE intervention, mice with PSCI had significantly improved water maze performance, better induction of hippocampal long-term potentiation (LTP), enhanced function of the basal forebrain-hippocampus cholinergic circuits of contralateral side of stroke and relatively balanced acetylation homeostasis compared to those of PSCI mice in standard environments (SE). In addition, PSCI mice in EE expressed much higher levels of p-CREB and CBP than in SE, and the chromatins bound to M-type promoter of ChAT gene were more acetylated. These results demonstrate that EE plays an important role in the improvement of PSCI and the underlying mechanism may involve in the acetylation of histones bound to the ChAT gene promoter in cholinergic circuits. [ABSTRACT FROM AUTHOR]

Tectochrysin, a flavonoid compound, can be isolated from propolis, Alpinia oxyphylla Miq , and Lychnophora markgravii. This study evaluated the efficacy of tectochrysin in the treatment of shrimp tropomyosin (ST)-induced mouse asthma. Mice were sensitized with intraperitoneal (i.p.) injection of ST together with aluminum hydroxide as an adjuvant to establish a mouse model of asthma. Mice were i.p.-treated daily with tectochrysin. IgE levels in plasma, Th2 cytokines from both bronchoalveolar lavage (BAL) fluid and splenocytes, and CD200R on basophils in peripheral blood were measured. Histological analyses of lung tissues and accumulation of leukocytes in BAL fluid were performed. Lung eosinophil peroxidase, catalase and glutathione peroxidase activities were examined. ST was found to markedly increase eosinophilic inflammation and Th2 response in mice. Tectochrysin treatment reduced the level of IgE in plasma, the percentage of eosinophils in total white blood cells in peripheral blood, the total number of cells in BAL fluid, and eosinophil peroxidase activity in lung tissues. Tectochrysin attenuated ST-induced infiltration of eosinophils and epithelial mucus secretion in lung tissues and suppressed the overproduction of Th2 cytokines (IL-4 and IL-5) in BAL fluid. Tectochrysin also attenuated Th2 cytokine (IL-4 and IL-5) production from antigen-stimulated murine splenocytes in vitro , decreased the expression of CD200R on basophils in peripheral blood of asthmatic mice and inhibited IL-4 secretion from IgE-sensitized RBL-2H3 cells. In addition, tectochrysin enhanced catalase and glutathione peroxidase activities in lung tissues. Our findings demonstrate that TEC ameliorates allergic airway inflammation by suppressing Th2 response and oxidative stress. [ABSTRACT FROM AUTHOR]

• Shrimp tropomyosin (ST) induces more intense immunological and histopathological changes than ovalbumin in mice. • ST-induced allergy without adjuvants exhibits several hallmarks of mouse asthma. • ST-induce model in mice is a suitable model of allergic asthma that offers significant advantages over OVA-induced model due to the availability of inexpensive, reliable, and easy-to-establish method. Allergic asthma remains an important worldwide health issue. Animal models are valuable for understanding the pathophysiological mechanisms of asthma and the development of effective therapeutics. This study aims to develop an alternative murine model induced by shrimp tropomyosin (ST) instead of ovalbumin (OVA). To investigate responses to short-term exposure to antigens, mice were sensitized with intraperitoneal injections of ST or ST plus aluminum adjuvant on days 0, 7, 14 followed by an intranasal challenge with ST for seven consecutive days. We reveal that sensitization with ST alone or ST plus aluminum induces significant levels of serum total IgE and ST-specific IgE in mice. Challenge results show that ST causes severe eosinophilic airway inflammation. Histology analysis of the lung tissues demonstrates airway inflammation and mucus hypersecretion within the bronchi in mice exposed to ST. Analysis of the cell composition in bronchoalveolar lavage fluid (BALF) shows a significant increase in eosinophil count in ST alone and ST plus aluminum groups. We also detect increased CD4+ T lymphocytes in lung tissues and production of helper T cell type 2-associated cytokines (IL-4 and IL-5) in BALF. In addition, airway hyperresponsiveness to methacholine in ST alone and ST plus aluminum groups is much higher than that in control groups. For the chronic model, mice were sensitized by ST or ST plus aluminum adjuvant for 3 weeks and challenged with ST for 6 weeks. We find severe structural changes in animals upon prolonged exposure to ST, including goblet cell hyperplasia, collagen deposition, and smooth muscle thickening. In conclusion, ST-induced asthma is a simple murine model for studying pathogenesis of asthma and evaluating new therapeutic drugs. [ABSTRACT FROM AUTHOR]