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Targeted ablation of cardiac sympathetic neuron attenuates sympathetic remodelling and improves ventricular electrical remodelling in the chronic phase of MI. These data suggest that TACSN may be a novel approach to treating ventricular arrhythmias.

Myeloid differentiation 1 (MD‐1) is a secreted protein that regulates the immune response of B cell through interacting with radioprotective 105 (RP105). Disrupted immune response may contribute to the development of cardiac diseases, while the roles of MD‐1 remain elusive. Our studies aimed to explore the functions and molecular mechanisms of MD‐1 in obesity‐induced cardiomyopathy. H9C2 myocardial cells were treated with free fatty acid (FFA) containing palmitic acid and oleic acid to challenge high‐fat stimulation and adenoviruses harbouring human MD‐1 coding sequences or shRNA for MD‐1 overexpression or knockdown in vitro. MD‐1 overexpression or knockdown transgenic mice were generated to assess the effects of MD‐1 on high‐fat diet (HD) induced cardiomyopathy in vivo. Our results showed that MD‐1 was down‐regulated in H9C2 cells exposed to FFA stimulation for 48 hours and in obesity mice induced by HD for 20 weeks. Both in vivo and in vitro , silencing of MD‐1 accelerated myocardial function injury induced by HD stimulation through increased cardiac hypertrophy and fibrosis, while overexpression of MD‐1 alleviated the effects of HD by inhibiting the process of cardiac remodelling. Moreover, the MAPK and NF‐κB pathways were overactivated in MD‐1 deficient mice and H9C2 cells after high‐fat treatment. Inhibition of MAPK and NF‐κB pathways played a cardioprotective role against the adverse effects of MD‐1 silencing on high‐fat stimulation induced pathological remodelling. In conclusion, MD‐1 protected myocardial function against high‐fat stimulation induced cardiac pathological remodelling through negative regulation for MAPK/NF‐κB signalling pathways, providing feasible strategies for obesity cardiomyopathy.

Objective: Today, more and more evidence suggests that Foxk proteins (Foxk1 and Foxk2) work as transcriptional repressors in different kinds of cancer, but whether Foxk1 has a role in mediating tumorigenesis in breast cancer, the evidence is rare. Methods: MCF-7 cells transfected with shFoxk1 displayed a mesenchymal morphology and reduced the expression of E-cadherin, and increased the expression of N-cadherin. Transwell invasion assay and living imaging assay show that the overexpression of Foxk1 could inhibit metastasis in vitro and in vivo. Ribonucleic acid sequencing revealed that the knockdown of Foxk1 resulted in the up-regulation of different oncogenes, which was implicated in metastasis and tumor angiopoiesis. Quantitative chromatin immunoprecipitation, chromatin immunoprecipitation and Luciferase reporter assays suggested that Foxk1 could bind to the promoter of epithelial-mesenchymal transition inducer Twist and vascular endothelial growth factor, VEGF. Mass Spectrometry, co-immunoprecipitation assays and glutathione-S-transferase pull-down assay detected that Foxk1 was physically associated with Ten-eleven translocation 1, TET1, in vivo and in vitro. Results: We reported that the mean expression level of Foxk1 in breast cancer was significantly lower than the adjacent noncarcinoma tissue. The higher Foxk1 expression was associated with better prognosis. Endothelial tube formation assays indicated that Foxk1 might regulate breast cancer angiogenesis through transcriptional repression of vascular endothelial growth factor. Furthermore, in vivo magnetic resonance imaging revealed the overexpression of Foxk1 could enhance the detection of the tumors. Further, a strong negative correlation was observed between Foxk1 and Twsit or between Foxk1 and vascular endothelial growth factor, and the higher Foxk1 expression is correlated with better over all survivals and better relapse-free survivals. Conclusions: Together, our data indicated the function of Foxk1 as a tumor suppressor in facilitating angiogenesis and metastasis in breast cancer.

Aim-Oxidative stress and the inflammatory response contribute to the progression of cardiovascular disease. The present study aimed to investigate whether the mitochondrial-derived peptide MOTS-c could alleviate H 2 O 2 -induced oxidative stress and inflammatory status in H9c2 cells through activation of nuclear factor erythroid 2-related Factor 2 (Nrf2)/antioxidative response element (ARE) and inhibition of the NF-jB pathway. Methods-Rat H9c2 cardiomyocytes were obtained, and 10, 20 or 50 lM MOTS-c was pretreated for 24 h before treatment with H 2 O 2. Then, the cell was treated with 100 lM H 2 O 2 for 1 h to induce oxidative stress. An inhibition model of sh-Nrf2 was constructed via a lentivirus expression system, and an activation model of NF-jB was achieved using phorbol 12-myristate-13-acetate (PMA). Cell viability was determined using a Cell Counting kit-8 assay. Relative measurement of relative protein and mRNA expression used western blotting and qRT-PCR, respectively. Intracellular reactive oxygen species (ROS) levels were detected using dichlorodihydrofluorescein diacetate, and malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined via commercial kits. The protein expression and distribution in the cells were visualized by immunofluorescence analysis. Enzyme-linked immunosorbent assay was used to detect the levels of inflammatory cytokines, including TNF-a, IL-6 and IL-1b. Results-We found that H 2 O 2 treatment significantly decreased cell viability and the level of SOD, increased the levels of ROS and MDA, and upregulated the expression of inflammatory cytokines, including TNF-a, IL-6 and IL-1b, in H9c2 cells. The expression levels of Nrf2, HO-1 and NQO-1 were significantly downregulated in the H 2 O 2 , while the phosphorylation of NF-jBp65 was promoted by H 2 O 2 . However, pretreatment with MOTS-c significantly reversed H 2 O 2 -induced damage in H9c2 cells. Moreover, both inhibition of the Nrf2/ARE pathway and activation of the NF-jB pathway significantly decreased the effects of MOTS-c, suggesting that MOTS-c might play a role in alleviating oxidative damage via the Nrf2/ARE and NF-jB pathways. Conclusions-Our investigation indicated that MOTS-c could protect against H 2 O 2 -induced inflammation and oxidative stress in H9c2 cells by inhibiting NF-jB and activating the Nrf2/ARE pathways.