Abstract
5-Methylcytosine (m5C) plays an extremely important role in the basic biochemical process. With the great increase of identified m5C sites in a wide variety of organisms, their epigenetic ...roles become largely unknown. Hence, accurate identification of m5C site is a key step in understanding its biological functions. Over the past several years, more attentions have been paid on the identification of m5C sites in multiple species. In this work, we firstly summarized the current progresses in computational prediction of m5C sites and then constructed a more powerful and reliable model for identifying m5C sites. To train the model, we collected experimentally confirmed m5C data from Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Arabidopsis thaliana, and compared the performances of different feature extraction methods and classification algorithms for optimizing prediction model. Based on the optimal model, a novel predictor called iRNA-m5C was developed for the recognition of m5C sites. Finally, we critically evaluated the performance of iRNA-m5C and compared it with existing methods. The result showed that iRNA-m5C could produce the best prediction performance. We hope that this paper could provide a guide on the computational identification of m5C site and also anticipate that the proposed iRNA-m5C will become a powerful tool for large scale identification of m5C sites.
Regulatory T (Treg) cells are crucial for peripheral immune tolerance and prevention of autoimmunity and tissue damage. Treg cells are inherently defined by the expression of the transcription factor ...Foxp3, which enforces lineage development and immune suppressive function of these cells. Under various conditions as observed in autoimmunity, cancer and non-lymphoid tissues, a proportion of Treg cells respond to specific environmental signals and display altered stability, plasticity and tissue-specific heterogeneity, which further shape their context-dependent suppressive functions. Recent studies have revealed that metabolic programs play pivotal roles in controlling these processes in Treg cells, thereby considerably expanding our understanding of Treg cell biology. Here we summarize these recent advances that highlight how cell-extrinsic factors, such as nutrients, vitamins and metabolites, and cell-intrinsic metabolic programs, orchestrate Treg cell stability, plasticity, and tissue-specific heterogeneity. Understanding metabolic regulation of Treg cells should provide new insight into immune homeostasis and disease, with important therapeutic implications for autoimmunity, cancer, and other immune-mediated disorders.
Scope
A growing number of studies have reported the effects of eicosapentaenoic acid (EPA) and terrestrial phospholipids on ameliorating mood disorders. Marine‐derived EPA‐enriched phospholipids ...(EPA‐PL) exhibit the structural characteristics of EPA and phospholipids. However, the effect of dietary EPA‐PL, and the differences between amphiphilic EPA‐PL and lyophobic EPA on mood disorders had not been studied.
Methods and Results
A comparative investigation to determine the effects of dietary EPA‐enriched ethyl ester (EPA‐EE) and EPA‐PL on improving depression‐ and anxiety‐like behavior in a mouse model is performed, induced by 4 week chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge. It is found that dietary 4 week 0.6% (w/w) EPA‐PL rescued depression‐ and anxiety‐like behavior to a greater extent than did EPA‐EE. Moreover, dietary EPA‐PL significantly reduced the immobility time by 56.6%, close to the normal level, in forced swimming test, which revealed a reversal of depression‐like behavior. Further studies revealed that dietary EPA‐PL regulated immunity, monoamine systems, and the hypothalamic–pituitary–adrenal (HPA) axis by multi‐target interactions, including inhibition of neuroinflammation and apoptosis.
Conclusion
EPA‐PL exerted superior effects to EPA‐EE in alleviating depression‐ and anxiety‐like behavior. The data suggest potential novel candidate or targeted dietary patterns to prevent and treat mood disorder.
Comparatively investigated the effects of dietary EPA‐EE and EPA‐PL on improving depression‐ and anxiety‐like behavior in a mouse model, induced by chronic unpredictable mild stress (CUMS) couple with LPS challenge. The results reveal that EPA‐PL exerts superior effects to EPA‐EE in alleviating depression‐ and anxiety‐like behavior by regulating immunity and neuroinflammation, monoamine systems, and the hypothalamic–pituitary–adrenal (HPA) axis.
Alterations in circular RNA (circRNA) expression have a vital impact on the biological processes in cancer. Moreover, the expression pattern and roles of circRNAs in hepatocellular cancer (HCC) ...remain unclear. This study performed qRT-PCR to determine the regulated circRNAs in HCC tissues and cell lines. CCK8, 5-ethynyl-2′-deoxyuridine (EdU) assay, colony formation, cell cycle assay, apoptotic assay, transwell, and wound healing assay were conducted to assess the function of hsa_circ_0091570 or miR-1307 on cell proliferation, apoptosis, and migration in vitro. Mouse xenograft models were used to measure the functions of hsa_circ_0091570 in vivo. The decreased expression of hsa_circ_0091570 was associated with the pathological staging of HCC patients. Furthermore, inhibition of hsa_circ_0091570 promoted cell proliferation and migration, blocked cell apoptosis in HCC cell lines, and promoted tumor growth in the mouse xenograft model. RNA immunoprecipitation assay verified the interaction of hsa_circ_0091570 and miR-1307. The miR-1307 inhibitor inhibited the function induced by hsa_circ_0091570 siRNA. Overall, hsa_circ_0091570 sponge miR-1307 as a ceRNA and regulate ISM1 expression by exerting functional roles in HCC.
•Expression of hsa_circ_0091570 is associated with the pathological stage of patients with hepatocellular cancer (HCC).•hsa_circ_0091570 inhibits cell proliferation and migration in HCC cell lines.•hsa_circ_0091570 acts as a competing endogenous RNA to suppress HCC progression by sponging miR-1307.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of ...lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.
We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.
We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.
Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.
Helium (He) bubbles are typical radiation defects in structural materials in nuclear reactors after high dose energetic particle irradiation. In the past decades, extensive studies have been ...conducted to explore the dynamic evolution of He bubbles under various conditions and to investigate He-induced hardening and embrittlement. In this review, we summarize the current understanding of the behavior of He bubbles in metals; overview the mechanisms of He bubble nucleation, growth, and coarsening; introduce the latest methods of He control by using interfaces in nanocrystalline metals and metallic multilayers; analyze the effects of He bubbles on strength and ductility of metals; and point out some remaining questions related to He bubbles that are crucial for design of advanced radiation-tolerant materials.
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