Epigenetic control of transposable elements and cell fate decision.

Transposable elements (TEs) are the most prevalent elements in mammalian genomes. Although potential risks for genome stability, they are a pool of potential regulatory sequences, chromatin control elements, protein-coding genes, and substrates for evolutionary processes. Consequently, a delicate balance is maintained between the potential benefits and deleterious aspects of TEs, and this balance is mediated by the epigenetic regulatory system. In this review, we introduce the role of heterochromatin associated epigentic modifications such as histone 3 lysine 9 trimethylation (H3K9me3) and DNA methylation in the silencing of TEs as well as epigenetic modifications such as histone 3 lysine 4 monomethylation (H3K4me1) and histone 3 lysine 27 acetylation (H3K27ac) in activation of TEs. Further, we elaborate the functions of TEs as binding sites of transcription factors and as anchors of chromosomal conformation in regulation of gene expression. We introduce the impact of TEs on the process of cell fate determination including natural embryonic development in vivo and artificial cell fate transition in vitro. We discuss the main challenges associated with computational TEs analysis and TEs functions exploration, as well as the different experimental and computational strategies in studying these processes. In all, this article provides a comprehensive review of the research advances and existing problems in study of transposable elements in epigenetic regulatory mechanisms, gene transcriptional regulation, and cell fate determination, thereby providing some references for researchers in the fields.

Upper gastrointestinal hemorrhage and thoracic aortic aneurysm rupture as presenting signs of Behçet disease: A case report.

INTRODUCTION: Behçet disease (BD) is an autoimmune disorder characterized by oral aphthosis, genital aphthosis, ocular lesions, and arthritis. However, other fatal complications are often misdiagnosed, which implies that the early diagnosis of the disease is important for a good prognosis. PATIENT CONCERNS: A 51-year-old man complained of hematemesis for 5 hours and syncope once. DIAGNOSIS: BD as demonstrated by esophageal ulcer and aortic aneurysm rupture. INTERVENTIONS: Surgeries were conducted to repair the thoracic aortic aneurysm, proton-pump inhibitor was used to reduce acid secretion, antibiotics were applied for anti-infective therapy, and immunosuppressor was administered to control the injuries of BD. OUTCOMES: The patient was discharged and his medication dosage was reduced gradually until the minimum maintenance dose. In the follow-ups, the gastric ulcer and vascular aneurysm were not found. CONCLUSION: We presented a rare case of BD with the concurrence of huge esophageal ulcer and thoracic aortic aneurysms rupture, which helped us to diagnose BD at the early stage, while confronting atypical manifestations.

Ufm1 inhibits LPS-induced endothelial cell inflammatory responses through the NF-κB signaling pathway.

Endothelial cell dysfunction and inflammatory responses are important early contributors to the occurrence and development of atherosclerosis (AS), which still remains to be decoded. Ubiquitin-fold modifier 1 (Ufm1) is a new member of the ubiquitin-like protein family, and its biological function remains largely unknown, particularly in endothelial cell injury and inflammatory responses. In the present study, we showed that Ufm1 was highly expressed in both the nucleus and cytoplasm of human umbilical vein endothelial cells (HUVECs). We also demonstrated that the Ufm1 expression level was increased following lipopolysaccharide (LPS)­induced inflammation in HUVECs. Moreover, overexpression of Ufm1 in HUVECs alleviated the inflammatory responses induced by LPS treatment. Additionally, we found that Ufm1 overexpression inhibited the nuclear translocation of nuclear factor-κB (NF-κB) after LPS treatment, suggesting its implication in the LPS/Toll-like receptor 4 (TLR4)/NF-κB pathway. Taken together, in addition to decoding its expression pattern in endothelial cells, we showed for the first time that Ufm1 is upregulated in LPS-induced inflammation and Ufm1 plays an inhibitory role in inflammatory responses by targeting NF-κB nuclear translocation. Thus, Ufm1 may be a novel gene that protects against inflammatory responses.

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway.

AIM: Macrophage foam cell formation is the most prominent characteristic of the early stages of atherosclerosis. Ubiquitin Fold Modifier 1 (UFM1) is a new member of the ubiquitin-like protein family, and its underlying mechanism of action in macrophage foam cell formation is poorly understood. Our current study focuses on UFM1 and investigates its role in macrophage foam cell formation. METHODS: Using real-time quantitative PCR (qRT-PCR) and western blot analysis, we first analyzed the UFM1 expression in mouse peritoneal macrophages (MPMs) from ApoE－/－ mice in vivo and in human macrophages treated with oxLDL in vitro. Subsequently, the effects of UFM1 on macrophages foam cell formation were determined by Nile Red staining and direct lipid analysis. We then examined whether UFM1 affects the process of lipid metabolism in macrophages. Lastly, with the method of small interfering RNA (siRNA), we delineated the mechanism of UFM1 to attenuate lipid accumulation in THP-1 macrophages. RESULTS: UFM1 is dramatically upregulated under atherosclerosis conditions both in vivo and in vitro. Moreover, UFM1 markedly decreased macrophage foam cell formation. Mechanistic studies revealed that UFM1 increased the macrophage cholesterol efflux, which was due to the increased expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1). Furthermore, the upregulation of ABCA1 and ABCG1 by UFM1 resulted from liver X receptor α (LXRα) activation, which was confirmed by the observation that LXRα siRNA prevented the expression of ABCA1 and ABCG1. Consistent with this, the UFM1-mediated attenuation of lipid accumulation was abolished by such inhibition. CONCLUSIONS: Taken together, our results showed that UFM1 could suppress foam cell formation via the LXRα-dependent pathway.

Factors associated with efficacy of pegylated interferon-α plus ribavirin for chronic hepatitis C after renal transplantation.

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease after renal transplantation (RT), which reduces both graft and patient survival. After RT, the most widely used approach is interferon (IFN)-based therapy of hepatitis C which may be unsatisfactory with both poor efficacy and an increasing risk of allograft rejection. Thus, it is not recommended unless patients develop fibrosing cholestatic hepatitis. Several recent studies, however, suggest that treatment was possible with preservation of both renal and liver functions. From the limited studies on HCV infection after RT, several factors have been identified as important tools for the management of therapy in these patients. Infection with HCV genotypes 2 and 3, low baseline viral load and absence of advanced fibrosis/cirrhosis in the liver are associated with a sustained virologic response (SVR). After initiation of treatment, initial viral decline with undetectable HCV-RNA at week 4 of therapy (RVR) is the best predictor of SVR independent of HCV genotype. Furthermore, some factors must be taken into consideration in order to avoid allograft rejection, such as the time between transplantation and therapy for HCV, the dose and duration of regimen and renal function. Careful evaluation of predictions of stable renal function and SVR for those patients helps to reduce inefficient treatment regimes and to increase the cure rate in addition to reducing the possible risk. In this review, the latest information was collected and we focus on the discussion of the factors influencing the attainment of SVR after RT.