Upregulated expression of a TOR2A gene product-salusin-ß in the paraventricular nucleus enhances sympathetic activity and cardiac sympathetic afferent reflex in rats with chronic heart failure induced by coronary artery ligation.

AIM: Enhanced cardiac sympathetic afferent reflex (CSAR) promotes sympathetic hyperactivation in chronic heart failure (CHF). Salusin-ß is a torsin family 2 member A (TOR2A) gene product and a cardiovascular active peptide closely associated with cardiovascular diseases. We aimed to determine the roles of salusin-ß in the paraventricular nucleus (PVN) in modulating enhanced CSAR and sympathetic hyperactivation in rats with CHF induced by coronary artery ligation and elucidate the underlying molecular mechanisms. METHODS: CSAR was evaluated based on the responses of mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) to the epicardial administration of capsaicin in rats under anesthesia. RESULTS: Salusin-ß protein expression was upregulated in the PVN of the CHF compared with sham-operated rats. Salusin-ß microinjection into the PVN dose-dependently increased MAP and RSNA and enhanced CSAR, while anti-salusin-ß IgG exerted opposite effects. The effect of salusin-ß was inhibited by reactive oxygen species (ROS) scavenger or NAD(P)H oxidase inhibitor but promoted by superoxide dismutase inhibitor. The effect of anti-salusin-ß IgG was interdicted by nitric oxide (NO) synthase inhibitor. Furthermore, chronic salusin-ß gene knockdown in PVN attenuated CSAR, reduced sympathetic output, improved myocardial remodeling and cardiac function, decreased NAD(P)H oxidase activity and ROS levels, and increased NO levels in the CHF rats. CONCLUSION: Increased salusin-ß activity in the PVN contributes to sympathetic hyperactivation and CSAR in CHF by inhibiting NO release and stimulating NAD(P)H oxidase-ROS production. Reducing endogenous central salusin-ß expression might be a novel strategy for preventing and treating CHF in the future.

Effects of Amifostine Pre-treatment on MIRNA, LNCRNA, and MRNA Profiles in the Hypothalamus of Mice Exposed to 60Co Gamma Radiation.

There is increasing evidence that the expression of non-coding RNA and mRNA (messenger RNA) is significantly altered following high-dose ionizing radiation (IR), and their expression may play a critical role in cellular responses to IR. However, the role of non-coding RNA and mRNA in radiation protection, especially in the nervous system, remains unknown. In this study, microarray profiles were used to determine microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA expression in the hypothalamus of mice that were pretreated with amifostine and subsequently exposed to high-dose IR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. We found that fewer miRNAs, lncRNAs, and mRNAs were induced by amifostine pre-treatment in exposed mice, which exhibited antagonistic effects compared to IR, indicating that amifostine attenuated the IR-induced effects on RNA profiles. GO and KEGG pathway analyses showed changes in a variety of signaling pathways involved in inflammatory responses during radioprotection following amifostine pre-treatment in exposed mice. Taken together, our study revealed that amifostine treatment altered or attenuated miRNA, lncRNA, and mRNA expression in the hypothalamus of exposed mice. These data provide a resource to further elucidate the mechanisms underlying amifostine-mediated radioprotection in the hypothalamus.

Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer.

Purpose: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the overall biological roles and clinical significance of most lncRNAs in gastric carcinogenesis are not fully understood. We investigated the clinical significance, biological function, and mechanism of LINC01234 in gastric cancer.Experimental Design: First, we analyzed LINC01234 alterations in gastric cancerous and noncancerous tissues through an analysis of sequencing data obtained from The Cancer Genome Atlas. Next, we evaluated the effect of LINC01234 on the gastric cancer cell proliferation and apoptosis, and its regulation of miR-204-5p by acting as a competing endogenous RNA (ceRNA). The animal model was used to support the in vitro experimental findings.Results: We found that LINC01234 expression was significantly upregulated in gastric cancer tissues and was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and shorter survival time. Furthermore, knockdown of LINC01234-induced apoptosis and growth arrest in vitro and inhibited tumorigenesis in mouse xenografts. Mechanistic investigations indicated that LINC01234 functioned as a ceRNA for miR-204-5p, thereby leading to the derepression of its endogenous target core-binding factor ß (CBFB).Conclusions: LINC01234 is significantly overexpressed in gastric cancer, and LINC01234-miR-204-5p-CBFB axis plays a critical role in gastric cancer tumorigenesis. Our findings may provide a potential new target for gastric cancer diagnosis and therapy. Clin Cancer Res; 24(8); 2002-14. ©2018 AACR.

Cholecystectomy does not significantly increase the risk of fatty liver disease.

AIM: To investigate the relationship between cholecystectomy and fatty liver disease (FLD) in a Chinese population. METHODS: A total of 32428 subjects who had voluntarily undergone annual health checkups in the Second Affiliated Hospital of Nanjing Medical University from January 2011 to May 2013 were included in this study. Basic data collection, physical examination, laboratory examination, and abdominal ultrasound examination were performed. RESULTS: Subjects undergoing cholecystectomy were associated with greater age, female sex, higher body mass index, and higher levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglycerides. However, no significant differences were found in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, albumin, and serum uric acid. The overall prevalence of FLD diagnosed by ultrasonography was high at 38.4%. The prevalence of FLD was significantly higher for subjects who had undergone cholecystectomy (46.9%) than those who had not undergone cholecystectomy (38.1%; χ(2) test, P < 0.001). Cholecystectomy was positively associated with FLD (OR = 1.433, 95%CI: 1.259-1.631). However, after adjusting for possible factors associated with FLD, multivariate regression analysis showed that the association between cholecystectomy and FLD was not statistically significant (OR = 1.096; 95%CI: 0.939-1.279). CONCLUSION: According to our study results, cholecystectomy may not be a significant risk factor for FLD.