Circ_0001971 regulates oral squamous cell carcinoma progression and chemosensitivity by targeting miR-194/miR-204 in vitro and in vivo.

OBJECTIVE: Circular RNAs (circRNAs) play a wide role in human cancers, including oral squamous cell carcinoma (OSCC). The purpose of this study was to investigate the biological functions of circ_0001971 and associated mechanisms in OSCC. MATERIALS AND METHODS: The expression of circ_0001971, miR-194, and miR-204 was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation and viability were assessed using cell counting kit-8 (CCK-8) assay. Cell migration and invasion were examined using the transwell assay. Cell apoptosis was monitored by flow cytometry assay. The protein levels of proliferation marker (CyclinD1), epithelial mesenchymal-transition (EMT) markers (E-cadherin (E-cad) and N-cadherin (N-cad)) and apoptosis markers (Cleaved-caspase-3 (Cleaved-cas-3) and Cleaved-caspase-9 (Cleaved-cas-9)) were measured by Western blot. The relationship between circ_0001971 and miR-194 or miR-204 was predicted by online tool starBase and verified by the Dual-Luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Tumor formation assay in nude mice was conducted to observe the role of circ_0001971 in vivo. RESULTS: The expression of circ_0001971 was significantly increased in tumor tissues and cell lines. Circ_0001971 knockdown inhibited cell proliferation, migration, and invasion but promoted cisplatin (DDP) sensitivity and cell apoptosis. It was confirmed that miR-194 and miR-204 were targets of circ_0001971, and miR-194 inhibition or miR-204 inhibition reversed the effects of circ_0001971 knockdown in OSCC cells. Moreover, circ_0001971 knockdown impeded tumorigenesis and development in vivo. CONCLUSIONS: Circ_0001971 regulates cell proliferation, migration, invasion, apoptosis, and chemosensitivity of OSCC by interacting with miR-194 and miR-204 in vitro and in vivo. We provided a theoretical basis for the action mechanism of circ_0001971 on OSCC progression and chemosensitivity.

Hepcidin protects pulmonary artery hypertension in rats by activating NF-κB/TNF-α pathway.

OBJECTIVE: The pulmonary artery hypertension (PAH) model was established in rats in this study. Therefore, we aimed to elucidate the protective role of Hepcidin in PAH rats and its underlying mechanism. MATERIALS AND METHODS: 24 male Sprague Dawley (SD) rats were randomly divided into sham group, PAH group and Hepcidin group, with 8 rats in each group. After animal procedures, hemodynamic parameters and right ventricular hypertrophy indexes were determined in rats. Cytokines in serum samples of rats were detected by enzyme-linked immunosorbent assay (ELISA). Pathological lesions in lung tissues were observed by hematoxylin and eosin (H&E) staining. Finally, Western blot was conducted to detect the protein expressions of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and monocyte chemotactic protein-1 (MCP-1) in lung tissues of rats. RESULTS: Compared with sham group, mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) were significantly elevated in rats of PAH group (p<0.05). On the contrary, mPAP and RVSP in rats of Hepcidin group were both significantly lower than PAH group (p<0.05). Hepcidin treatment attenuated PAH-induced pathological lesions in lung tissues. ELISA results elucidated that Hepcidin treatment significantly decreased serum levels of TGF-ß, TNF-α, IL-1ß, and IL-6. In addition, Western blot results demonstrated that protein levels of NF-κB, TNF-α, IL-1ß, VCAM-1, ICAM-1, and MCP-1 in Hepcidin group were remarkably lower than those of PAH group. CONCLUSIONS: Hepcidin alleviates inflammatory response in PAH rats by inhibiting NF-kB/ TNF-α pathway.

Nicotinamide pretreatment alleviates mitochondrial stress and protects hypoxic myocardial cells via AMPK pathway.

OBJECTIVE: The aim of this study was to explore the protective effect of nicotinamide on hypoxic cardiomyocytes and to investigate its possible mechanism. MATERIALS AND METHODS: Primary cardiomyocytes were used as study subjects. They were divided into three groups, including the blank group, control group and nicotinamide pretreatment group. Cell counting kit-8 (CCK-8) was used to detect cell viability. Lactate dehydrogenase (LDH) was used to detect cytotoxicity and flow cytometry was used to detect cell apoptosis. Polymerase Chain Reaction (PCR) and Western blot were used to measure the expressions of genes in adenosine monophosphate-activated protein kinase (AMPK) pathway. JC-1 detected the levels of mitochondrial membrane potential and reactive oxygen species (ROS). NAD was used for nicotinamide adenine dinucleotide (NAD)+, and NAD phosphate (NADP)+ levels. Adenosine triphosphate (ATP) assay was performed for the detection of intracellular energy metabolism. RESULTS: In the absence of oxygen, nicotinamide had a protective effect on primary cardiomyocytes. Meanwhile, nicotinamide could markedly inhibit the increase of caspase3 mRNA in cardiomyocyte apoptosis pathway, and suppress the expression of apoptotic proteins. Furthermore, it could significantly induce the increase of intracellular ATP and activate the AMPK pathway. The detection of mitochondria indicated that nicotinamide alleviated hypoxic cardiomyocytes. In addition, the mitochondrial membrane potential disrupted and inhibited mitochondrial oxidative stress levels. CONCLUSIONS: Nicotinamide pretreatment protects hypoxic cardiomyocytes and reduces intracellular mitochondrial stress. This protection may be related to the induction of the AMPK pathway and the increase of intracellular energy production.

Sonographic septation: a predictor of sequelae of tuberculous pleurisy after treatment.

BACKGROUND: Findings in the literature have been quite conflicting with respect to predicting residual pleural thickening (RPT) in tuberculous pleurisy (TP). The aim of this study was to determine which sonographic feature of TP might help in predicting the development of RPT. METHODS: Eighty-seven patients with TP were enrolled prospectively. The initial sonographic features were classified as anechoic, homogenously echogenic, complex non-septated and complex septated. The RPT level was measured 12 months after the start of antituberculosis (TB) treatment. Spirometry was performed 6 and 12 months after the start of anti-TB treatment. RESULTS: A higher odds of an RPT level >10 mm was found in patients with positive TB bacillus culture in pleural fluid (OR, 20.9; 95% CI, 2.2 to 198.0) and a complex septated sonographic pattern (OR, 145.0; 95% CI, 22.3 to 942.3). A complex septated sonographic pattern can predict RPT with a sensitivity of 80%, specificity of 96%, positive predictive value of 84% and negative predictive value of 94%. Patients with an RPT level >10 mm had a lower forced vital capacity than those without (75.4% (9.2%) predicted vs 83.2% (9.5%) predicted, p<0.01) CONCLUSION: A complex septated sonographic pattern is a useful sign to predict an RPT level >10 mm 1 year after the start of anti-TB treatment. An RPT level >10 mm is associated with a high probability of decreased lung volumes. Therefore, the initial sonographic feature is beneficial in predicting the sequelae of TP after treatment.

Pigtail drainage in the treatment of tuberculous pleural effusions: a randomised study.

BACKGROUND: Tuberculous pleurisy can result in obvious clinical symptoms, pleural fibrosis, and pleural thickening. Some studies of tuberculous pleurisy have suggested that symptomatic improvement and minimisation of sequelae can be achieved by completely draining the effusion during treatment, although the results have not been conclusive. METHODS: Sixty one patients with tuberculous pleurisy were divided into two groups; 30 patients received pigtail drainage combined with antituberculosis (TB) drug treatment and 31 received only anti-TB drugs. Outcome measurements were assessed for a period of 24 weeks after treatment and included symptom scores and the incidence of residual pleural thickening (RPT). RESULTS: Although the duration of dyspnoea was significantly shortened by the use of pigtail drainage (median 4 days (IQR 4-5) v 8 days (IQR 7-16), p<0.001), a comparison of combined mean (SD) visual analogue scale (VAS) scores showed no significant difference between the groups after one week of treatment (57.1 (33.2) v 68.5 (44.7) or at any time during the follow up period. The incidence of RPT of more than 10 mm in the group treated with pigtail drainage and anti-TB drugs was 26% compared with 28% in the group receiving drug treatment only. The incidence of RPT levels of more than 2 mm in the two groups was 50% and 51%, respectively. No statistical difference between the two groups in terms of forced vital capacity was found at the end of treatment (median (IQR) 85.5% (69-94) of predicted v 88% (78-96) of predicted). CONCLUSION: The addition of pigtail drainage to an effective anti-TB regimen is not clinically relevant and does not reduce the level of RPT.