Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases. Author summaryBRD4 has been well investigated in tumorigenesis for its contribution to chromatin remodeling and gene transcription. BRD4 inhibitors are used as promising chemotherapeutic drugs for cancer therapy. Here, we show a unique mechanism through which BRD4 inhibition broadly inhibits attachment of DNA and RNA viruses through DNA damage-dependent antiviral innate immune activation via the cGAS-STING pathway, in both cell culture and an animal model. STING-associated innate immune signaling has been considered to be a new possibility for cancer therapy, and STING agonists have been tested in early clinical trials. Our data identify BRD4 inhibitors as a potent therapy not only for viral infection but also for cancer immunotherapy. PLOS PATHOGENSPLOS Pathogens | https://doi.

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Ovarian cancer (OC) is one of the most common malignant tumors in female reproductive system and most OC cases are diagnosed at an advanced stage with the overall 5-year survival rate below 40%. The function of CD247 enhances T-cell antigen receptor (TCR) signaling cascade and it is necessary for assembling of the TCR/CD3 complex on the surface of T lymphocytes. It is well established that defective CD247 function leads to impaired activation of T cells upon engagement of the TCR. Flow cytometry was used to examine the difference of CD247+ T lymphocyte between the OC and ovarian cyst, immunohistochemistry analysis was used to investigate the correlation between CD247 expression and clinicopathologic features of epithelial OC patients. Our study showed that the expression of CD247 in peripheral blood lymphocytes from patients with OC is decreased compared with ovarian cyst patients and the expression of CD247 in tumor infiltrating lymphocytes with cancer tissue is decreased compared with adjacent tissues. We showed that abnormal expression of CD247 was related with differentiation and classification in OC. Our findings suggested that CD247-targeted treatment could be used as a potential therapeutic strategy for OC.

Non-alcoholic fatty liver disease (NAFLD) is the most common type of liver disease worldwide. Recent studies have reported that oxymatrine (OMT), an active monomer isolated from Sophora flavescens Ait. (kushen), ameliorates NAFLD in rats. In order to explore the possible molecular mechanism involved, we used an NAFLD rat model with hyperlipidemia, which had been established by feeding a high‑fructose diet (HFD) for eight weeks, and the model rats were subsequently treated with OMT (80 mg/kg/day) for a further four weeks. We evaluated the expression of genes and proteins regulating fatty acid oxidation and lipid export in the liver using quantitative (q)PCR and western blot analysis. The NAFLD model rats developed dyslipidaemia, hepatic steatosis and insulin resistance (IR). OMT administration for four weeks reduced body weight gain and visceral fat weight, decreased serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) and fasting serum insulin (FinS) levels and lowered liver TG contents. It also increased the glucose infusion rate (GIR), indicative of a reduction in IR. Moreover, OMT treatment markedly increased the mRNA and protein levels of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase 1A (CPT1A) and microsomal triglyceride transfer protein (MTTP). The beneficial effects of OMT were further confirmed by the observation of a decrease in lipid accumulation in the histology of the liver. Our results indicate that OMT may be used to treat NAFLD.