While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre- and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3-a histone modification typically associated with transcriptional repression-is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers but may be partially attributed to lower U2AF65 binding and weaker splicing-related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs and are enriched in lincRNAs that have been functionally characterized.

/pdf/chromatin-environment-transcriptional-regulation-and-3n4p8wz238.pdf

Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.

Studying epigenetics is expected to provide precious information on how environmental factors contribute to type 2 diabetes mellitus (T2DM) at the genomic level. With the progress of the whole-genome resequencing efforts, it is now known that 75–90% of the human genome was transcribed to generate a series of long non-coding RNAs (lncRNAs). While lncRNAs are gaining widespread attention as potential and robust biomarkers in the genesis as well as progression of several disease states, their clinical relevance and regulatory mechanisms are yet to be explored in the field of metabolic disorders including diabetes. Despite the fact that Asian Indians are highly insulin resistant and more prone to develop T2DM and associated vascular complications, there is virtually lack of data on the role of lncRNAs in the clinical diabetes setting. Therefore, we sought to evaluate a panel of lncRNAs and senescence-inflammation signatures in peripheral blood mononuclear cells (PBMCs) from patients with type 2 diabetes (T2DM; n = 30) compared to individuals with normal glucose tolerance (NGT; n = 32). Compared to control subjects, expression levels of lncRNAs in PBMCs from type 2 diabetes patients showed significantly (p < 0.05) increased levels of HOTAIR, MEG3, LET, MALAT1, MIAT, CDKN2BAS1/ANRIL, XIST, PANDA, GAS5, Linc-p21, ENST00000550337.1, PLUTO, and NBR2. In contrast, lncRNA expression patterns of THRIL and SALRNA1 were significantly (p < 0.05) decreased in patients with T2DM compared to control subjects. At the transcriptional level, senescence markers (p53, p21, p16, and β-galactosidase), proinflammatory markers (TNF-α, IL6, MCP1, and IL1-β), and epigenetic signature of histone deacetylase-3 (HDAC3) were significantly (p < 0.05) elevated in patients with type 2 diabetes compared to control subjects. Interestingly, mRNA expression of Sirt1 and telomere length were significantly (p < 0.05) decreased in patients with type 2 diabetes compared to control subjects. Majority of the altered lncRNAs were positively correlated with poor glycemic control, insulin resistance, transcriptional markers of senescence, inflammation, and HDAC3 and negatively correlated with telomere length. Logistic regression analysis revealed a significant association of altered lncRNA signatures with T2DM, but this association was lost after adjusting for insulin resistance (HOMA-IR) and senescence markers. Our study provides a clinically relevant evidence for the association of altered lncRNAs with poor glycemic control, insulin resistance, accelerated cellular senescence, and inflammation.

/pdf/linking-a-role-of-lncrnas-long-non-coding-rnas-with-insulin-47fut0ac42.pdf

Linking a role of lncRNAs (long non-coding RNAs) with insulin resistance, accelerated senescence, and inflammation in patients with type 2 diabetes.

Long Non-Coding RNAs: A Novel Paradigm for Toxicology.

An individual's risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation. This review aims to provide a general overview of lncRNA function with a focus on their role as key regulators of health and disease and as biomarkers of environmental exposure.

Environmental Health and Long Non-coding RNAs

MIAT promotes proliferation and hinders apoptosis by modulating miR-181b/STAT3 axis in ox-LDL-induced atherosclerosis cell models.

LncRNA MIAT: Myocardial infarction associated and more

Modern researches on Blood Stasis syndrome 1989-2015: A bibliometric analysis.

Objective: Extensive studies have shown that ERS may be implicated in the pathogenesis of DCM. We explored the therapeutic effects of lncRNAH19 on DCM and its effect on ERS-associated cardiomyocyte apoptosis. Methods: C57/BL-6j mice were randomly divided into 3 groups: non-DM group (controls), DM group (DCM), and lncRNAH19 overexpression group (DCM+H19 group). The effect of H19 on cardiac function was detected. The effect of H19 on cardiomyocyte apoptosis and cardiac fibrosis in DM was examined. Differentially expressed genes (DEGs) and activated pathways were examined by bioinformatics analysis. STRING database was applied to construct a PPI network using Cytoscape software. The expression of p-PERK, p-IRE1, ATF6, CHOP, cleaved caspase-3, -9, -12 and BAX proteins in cardiac tissue was used to determine the ERS-associated apoptotic indicators. We established the HG-stimulated inflammatory cell model. The expression of p-PERK and CHOP in HL-1 cells following HG was determined by immunofluorescence labeling. The effects of H19 on ERS and PI3K/AKT/mTOR pathway were also detected. Results: H19 improved left ventricular dysfunction in DM. H19 could reduce cardiomyocytes apoptosis and improve fibrosis in vivo. H19 could reduce the expression of p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX proteins in cardiac tissues. Furthermore, H19 repressed oxidative stress, ERS and apoptosis in vitro. Moreover, the effect of H19 on ERS-associated apoptosis might be rescued by LY294002 (the specific inhibitor for PI3K and AKT). Conclusion: H19 attenuates DCM in DM and ROS, ERS-induced cardiomyocyte apoptosis, which is associated with the activation of PI3K/AKT/mTOR signaling pathway.

/pdf/lncrna-h19-inhibits-er-stress-induced-apoptosis-and-improves-u1smdy3o.pdf

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis

Introduction Metformin (MET) can regulate glucose and lipid levels, and the gut microbiota may be involved in the control of metabolism. We hypothesized that MET alleviates glucolipid metabolism disorder by modulating gut microbiota and microbial metabolites. Research design and methods A total of 24 male C57BL/6 J mice were equally divided into three groups (normal control, model control (MC), and MET-treated groups). Model mice were established by feeding a high-fat diet for 6 weeks. The MET-treated group was administered MET solution (2.5 g/100 mL, 250 mg/kg). Fecal samples were collected to characterize the microbiota system using metagenomic shotgun sequencing and gas chromatography–time of flight–mass spectrometry analysis. Phenotypic and biochemical indices were obtained for further correlation analysis. Results Compared with the MC group, MET reduced the levels of weight, glucose, areas under the glucose curve in the glucose tolerance test, triglyceride (TG), and total cholesterol (TC). A decreasing abundance of bacteria, including Parabacteroides distasonis, and an increasing abundance of bacteria, including Bacteroides vulgatus, were observed in the MET-treated group. The 2-deoxytetronic acid declined after MET intervention and was positively correlated with species over-represented in the MC group and negatively correlated with species enriched in the MET-treated group. Additionally, species enriched in the MET-treated group negatively correlated with glucose, areas under the glucose curve in the glucose tolerance test, and TGs. Further, the correlation between the differential metabolites, which decreased after MET intervention, and the phenotypic indices was positive. Conclusions MET-induced restoration of intestinal homeostasis correlates with the amelioration of host glucolipid metabolism.

/pdf/metformin-modulates-the-gut-microbiome-in-a-mice-model-of-2q9ukbe3.pdf

Metformin modulates the gut microbiome in a mice model of high-fat diet-induced glycolipid metabolism disorder

Introduction Contrast-induced encephalopathy (CIE) is a complication associated with the administration of iodinated contrast, which usually happens minutes to hours after contact with contrast, and fully recovers within 72 h. The clinical manifestations of CIE are diverse, and the pathological mechanism is not explicit. Methods We report the case of a 66-year-old female who suffered from a delayed CIE following the administration of iodinated contrast agent. Symptoms were severe. Imaging examination, biochemical and etiological detection were performed timely. The course of neurological symptoms was atypical. Her complex complications of hypothyroidism and cerebrovascular abnormalities contributed to more challenges, which were also clues to the diagnosis. With prompt and active treatment, the patient recovered fully over 10 days. Discussion The diagnosis standard of CIE highly depends on the association with the contact of contrast and the exclusion of other nervous system diseases. Complicated clinical circumstances and individual specificity can lead to different clinical manifestations of CIE, making it even more difficult to diagnose and treat. Prompt and dynamic imaging examination would provide great value in the diagnosis and evaluation of CIE. Timely diagnosis and intervention may be the key to its satisfying prognosis.

/pdf/an-unusual-contrast-induced-encephalopathy-following-2ztdi8jk.pdf

Jiangquan Liao

Papers

LncRNA MIAT: Myocardial infarction associated and more

Modern researches on Blood Stasis syndrome 1989-2015: A bibliometric analysis.

LncRNA H19 inhibits ER stress induced apoptosis and improves diabetic cardiomyopathy by regulating PI3K/AKT/mTOR axis

Metformin modulates the gut microbiome in a mice model of high-fat diet-induced glycolipid metabolism disorder

An unusual contrast-induced encephalopathy following percutaneous coronary intervention in patients with cerebrovascular abnormalities: A case report