LncRNA SLC8A1-AS1 protects against myocardial damage through activation of cGMP-PKG signaling pathway by inhibiting SLC8A1 in mice models of myocardial infarction.

Extensive investigations into long noncoding RNAs (lncRNAs) in various diseases and cancers, including acute myocardial infarction (AMI) have been conducted. The current study aimed to investigate the role of lncRNA solute carrier family 8 member A1 antisense RNA 1 (SLC8A1-AS1) in myocardial damage by targeting solute carrier family 8 member A1 (SLC8A1) via cyclic guanosine 3',5'-monophosphate-protein kinase G (cGMP-PKG) signaling pathway in AMI mouse models. Differentially expressed lncRNA in AMI were initially screened and target relationship between lncRNA SLC8A1-AS1 and SLC8A1 was then verified. Infarct size, levels of inflammatory factors, biochemical indicators, and the positive expression of the SLC8A1 protein in AMI were subsequently determined. The expression of SLC8A1-AS1, SLC8A1, PKG1, PKG2, atrial natriuretic peptide, and brain natriuretic peptide was detected to assess the effect of SLC8A1-AS1 on SLC8A1 and cGMP-PKG. The respective contents of superoxide dismutase, lactate dehydrogenase (LDH), and malondialdehyde (MDA) were detected accordingly. Microarray data GSE66360 provided evidence indicating that SLC8A1-AS1 was poorly expressed in AMI. SLC8A1 was verified to be a target gene of lncRNA SLC8A1-AS1. SLC8A1-AS1 upregulation decreased levels of left ventricular end-systolic diameter, -dp/ dt max , interleukin 1ß (IL-1ß), IL-6, transforming growth factor α, nitric oxide, inducible nitric-oxide synthase, endothelial nitric-oxide synthase, infarct size, LDH activity and MDA content, and increased IL-10, left ventricular end-diastolic pressure and + dp/ dt max . Furthermore, the overexpression of SLC8A1-AS1 was noted to elicit an inhibitory effect on the cGMP-PKG signaling pathway via SLC8A1. In conclusion, lncRNA SLC8A1-AS1, by downregulating SLC8A1 and activating the cGMP-PKG signaling pathway, was observed to alleviate myocardial damage, inhibit the release of proinflammatory factors and reduce infarct size, ultimately protecting against myocardial damage.

Downregulated microRNA-224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF-ß/Smad pathway.

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR-224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF-ß/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR-224 inhibitor was prepared for investigating the effect of downregulated miR-224 on the contents of nitric oxide (NO) and endothelin-1 (ET-1), blood lipid levels and inflammatory factor levels in serum as well as the TGF-ß/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high-density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET-1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM-1 and MMP-2 protein expression, TGF-ß, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF-ß/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR-224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF-ß/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.

Tumour necrosis factor-α gene -308 G > A and -238 G > A polymorphisms are associated with susceptibility to irritable bowel syndrome and drug efficacy in children.

WHAT IS KNOWN AND OBJECTIVE: An imbalance in the genetically controlled pro- and anti-inflammatory cytokine production could potentially promote ongoing low-grade inflammation following an episode of acute gastroenteritis and, subsequently, could result in irritable bowel syndrome (IBS; post-infectious IBS, PI-IBS). Since there is very little known on the impact of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) on IBS, we conducted the present study with aims of determining the correlation between TNF-α gene polymorphisms (-308 G > A and -238 G > A) and susceptibility to IBS and drug efficacy in children. METHODS: Diarrhoea-predominant IBS patients and healthy subjects were recruited for DNA extraction. The genotypes were tested using polymerase chain reaction-restriction fragment length polymorphism. In addition to conventional symptomatic treatments, Live Combined Bifidobacterium, Lactobacillus and Enterococcus Powder and Montmorillonite Powder were administered to all the patients participating in the study for consecutive 4 weeks. The efficacy was evaluated 2 weeks after the withdrawal of the drugs. The association between gene polymorphism and drug efficacy was analysed by means of binary logistic regression analysis. RESULTS: Patients in the IBS group were susceptible to IBS with GA genotype and A allele of -308 G > A so were those with AA genotype and A allele of -238 G > A. The symptoms were also alleviated following treatment. The cure rate of patients with GA genotype of -308 G > A and AA genotype of -238 G > A was low. These findings suggested that the haplotype AA could potentially be associated with the cure rate of IBS patients. GA genotype of -308 G > A, AA genotype of -238 G > A, enterobacteria and 5-hydroxytryptamine in serum may act adversely, whereas bifidobacterial may be beneficial to the efficacy of IBS treatment. WHAT IS NEW AND CONCLUSION: The above findings evidently suggest that the frequency of TNF-α gene -308 G > A carrying GA genotype and A allele and -238 G > A carrying AA genotype and A allele is higher in children with IBS. Additionally, GA genotype of -308 G > A and AA genotype of -238 G > A may act adversely to the efficacy of IBS treatment, which may be a reference index for predicting the curative effect of IBS.

Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR.

BACKGROUND/AIMS: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. METHODS: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. RESULTS: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. CONCLUSIONS: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139.

BACKGROUND/AIMS: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. METHODS: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. RESULTS: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. CONCLUSION: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

Elevated serum levels of ghrelin and TNF-α in patients with cyanotic and acyanotic congenital heart disease.

BACKGROUND: The levels of ghrelin and tumor necrosis factor alpha (TNF-α) are considered biological markers of congenital heart diseases (CHD). The present meta-analysis was conducted to investigate the clinical significance of serum levels of ghrelin and TNF-α in children with (CHD). METHODS: Chinese and English scientific literature databases were searched to retrieve published studies relevant to ghrelin, TNF-α and CHD. Manual search was additionally employed to identify other relevant studies from cross-references. The retrieved studies were screened on the basis of our stringent inclusion and exclusion criteria to select high quality case-control studies for meta-analysis. RESULTS: We initially retrieved 108 published studies (20 in Chinese and 88 in English) from database searches. Finally, 6 case-control studies (5 in English and 1 in Chinese) were enrolled in our meta-analysis, and contained a total of 160 cyanotic congenital heart disease (CCHD) patients and 215 acyanotic congenital heart disease (ACHD) patients, along with 162 healthy controls. The results of meta-analysis showed that serum levels of ghrelin and TNF-α in CCHD or ACHD children were significantly higher than those in healthy controls. CONCLUSIONS: Our meta-analysis results showed that serum levels of ghrelin and TNF-α are elevated in children with CHD, and could be used as effective biologic markers in early diagnosis of CHD.

The complete mitochondrial genome of Leizhou goat Capra hircus (Bovidae; Caprinae).

Leizhou goat (Capra hircus) is one of the famous native goat breed in China. In this study, the 16,651 bp complete nucleotide sequence of Leizhou goat mitochondrial genome was sequenced for the first time. It contained 22 tRNA genes, 2 ribosomal RNA genes, 13 protein-coding genes.

Cardioprotective Effect of MicroRNA-21 in Murine Myocardial Infarction.

INTRODUCTION: To investigate the cardioprotective effect of MicroRNA-21 (miR-21) in murine myocardial infarction (MI). METHODS: Forty C57BL/6 male mice were divided into sham group, MI group, LV-GFP group, and miR-21 group. Mice in the MI group, LV-GFP group, and miR-21 group were subjected to MI by left anterior descending artery (LAD) ligation, while chest was opened/closed without ligation in sham group. In MI group, expression of miR-21 in the MI area and its surrounding areas was detected at 1st, 2nd, and 4th week after experiment. Subsequently, lentivirus expressing miR-21 and lentivirus that did not express miR-21 were transfected into mice left ventricular cavity of miR-21 group and LV-GFP group, respectively. Cardiac function, MI size, miR-21 expression, collagen I level, fibronectin content, number of α-SMA-positive cells, number of apoptotic cells, apoptosis-related factors were compared between the three groups. RESULTS: Compared with sham group, miR-21 levels in MI group were significantly decreased in the 1st week and 2nd week, but were almost the same in the 4th week. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in the miR-21 group improved compared to the LV-GFP group. In miR-21 group, myocardial infarct size reduced by 36.9% in comparison with LV-GFP group. Compared to sham group, miR-21 expression in the miR-21 group and LV-GFP group decreased significantly. In the miR-21 group, collagen I level, fibronectin content and number of α-SMA-positive cells of miR-21 decreased significantly compared to the LV-GFP group. The number of apoptotic cells in the MI areas of the miR-21 group was significantly less than the LV-GFP group. Compared with the LV-GFP group, Bcl-2 level and the ratio of Bcl-2 to Bax were significantly increased, and the levels of Bax and Caspase-3 decreased. CONCLUSIONS: Our results suggest miR-21 is an important regulatory molecule in the pathophysiology of MI.

Serum fetuin-A levels in patients with cardiovascular disease: a meta-analysis.

BACKGROUND: Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. METHOD: Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. RESULTS: Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD=1.36, 95%CI: 0.37-2.36, P=0.007). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD=1.73, 95%CI: 0.20-3.26, P=0.026), but not in Asians (SMD=1.04, 95%CI: -0.33-2.40, P=0.138). CONCLUSION: The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs.