Autophagy assuages myocardial infarction through Nrf2 signaling activation-mediated reactive oxygen species clear.

OBJECTIVE: The activation of autophagy was shown to shrink infarct size and mitigate cardiac dysfunction caused by myocardial infarction (MI). However, the underlying mechanisms remain largely unknown. As excessive generation of reactive oxygen species (ROS) deteriorates MI process and Nrf2 signaling exerts an antioxidant role, we explored whether autophagy assuaged MI through Nrf2 signaling activation-mediated ROS clear. MATERIALS AND METHODS: MI models were induced by ligation of the left descending coronary artery (LAD) in C57BL/6J mice or Nrf2 knockout mice (Nrf2-KO). Rapamycin and 3-methyladenine (3-MA) were used to activate and repress autophagy in MI mice, respectively. Aspirin, a cardioprotective drug was given to MI mice to evaluate its effects on autophagy. RESULTS: Compared with the MI group, rapamycin treatment remarkably decreased the infarct size, cell apoptosis and blood troponin I level, accompanied by reduced redox potential (Eh), ROS, malondialdehyde (MDA) and cytochrome C levels, and increased reduced glutathione (GSH) level. Also, rapamycin treatment increased the expressions of bcl-2, bcl-xL, HSP70, and HSP90. In addition, rapamycin treatment promoted the nuclear accumulation of Nrf2 protein. However, Nrf2 downregulation significantly impaired the effects of rapamycin on the reductions of infarct size, cell apoptosis, troponin I and ROS levels. Similarly, to rapamycin roles, aspirin treatment also remarkably reduced infarct size, cell apoptosis and troponin I in mice with MI surgery, as well as increased the expression level of LC3II/LC3I. CONCLUSIONS: This study demonstrated that autophagy enhancement contributed to the improvement of MI through Nrf2 signaling activation-mediated ROS clear.

[Expression of long-chain non-coding RNA LINC00152 in laryngeal squamous cell carcinoma and its clinical significance].

Objective:The aim of this study is to explore the relative expression level of LINC00152 in laryngeal squamous cell carcinoma（LSCC） and its clinical significance. Method:The relative expression levels of LINC00152 in LSCC cell lines and 36 paired LSCC specimens were measured by qRT-PCR method. And the correlations between the expression level of LINC00152 and the clinical features derived from LSCC patients were analyzed and compared through the independent sample t-test. Result:The relative expression level of LINC00152 was over-expressed in LSCC cell lines and cancerous tissues than that in paired adjacent normal tissues, and the difference was statistically significant（P=0.006）. Even the associations between LINC00152 expression level and clinicopathological features（P=0.044 for clinical stage, P=0.032 for pathological differentiation degree） were significantly. Conclusion:LINC00152 is highly expressed in LSCC and it may become a new tumor marker for the diagnosis and prognosis of LSCC.

GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury via upregulating LAS1 expression.

OBJECTIVE: This study aims at investigating whether GAS5 (grow arrest-specific 5) could promote cardiomyocyte apoptosis by upregulating LAS1 expression, thereby participating in the development of myocardial ischemia-reperfusion injury. MATERIALS AND METHODS: The expression level of GAS5 in H9c2 cells after hypoxia/reoxygenation (H/R) treatment was detected by quantitative Real time-polymerase chain reaction (qRT-PCR). Myocardial injury markers in H9c2 cells were evaluated using relative commercial kits, including activities of LDH (lactate dehydrogenase), MDA (malondialdehyde), SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The protein expressions of apoptosis-related genes and p38/MAPK pathway-related genes were detected by Western blot. The regulatory effects of GAS5 on the p38/MAPK pathway were assessed after treatment with p38/MAPK pathway inhibitor in H9c2 cells. RESULTS: QRT-PCR results showed that the expression levels of GAS5 and LAS1 in H/R-treated H9c2 cells were remarkably upregulated compared to those of controls. GAS5 overexpression increased activities of LDH, MDA, SOD and GSH-PX in H/R-treated H9c2 cells. Meanwhile, GAS5 overexpression reduced cell proliferation and apoptosis of H/R-treated cells. Western blot results suggested that the pro-apoptosis genes Bax and cytochrome C were upregulated, whereas the anti-apoptosis gene Bcl-2 was downregulated after GAS5 overexpression. The overexpression of LAS1 in H9c2 cells obtained the same results as GAS5 overexpression. Furthermore, the expressions of p-p38 and p-ERK were upregulated by GAS5 overexpression. SB203580, the p38/MAPK pathway inhibitor, could reverse the inhibited proliferation and increase apoptosis induced by overexpression of GAS5. CONCLUSIONS: GAS5 promotes myocardial apoptosis in myocardial ischemia-reperfusion injury by upregulating LAS1 expression via p38/MAPK pathway. GAS5 may be a potential therapeutic target for myocardial ischemia-reperfusion injury.

[Epigenetic regulations in laryngeal squamous cell carcinoma].

Laryngeal cancer, which is mainly consisted of laryngeal squamous cell carcinoma(LSCC), is one of the common neoplasms in head and neck. In spite the advantages in diagnose and treatment, the mortality of LSCC is still high in the past 20 years. Epigenetic regulations play a important role in LSCC. The aim of this review is to provide an update on the epigenetic regulations in LSCC, such as the methylation of chromatin, the pre- and post-regulation of transcription by microRNAs and/or long noncoding RNAs. The gene methylation can represses the expression of genes, and some histone and DNA methylation are associated with LSCC. Histone deacetylases also play a role in LSCC. MicroRNAs are about 22 nt in length, which inhibit or facilite the occurrence and development of LSCC by different mechanisms.Long noncoding RNAs(lncRNAs) , more than 200 nt in length, can modulate the LSCC in different levels, such as gene methylation modification, microRNA regulation. Based on the differences of epigenetic regulation, some characteristics may serve as markers of diagnose, and even facilitate the treatment of LSCC.

Totally thoracoscopic surgery for atrial myxomas resection and atrial septal defect repair.

OBJECTIVE: The purpose of this study is to compare the effectiveness and safety of thoracoscopic surgery and traditional median sternotomy. PATIENTS AND METHODS: 64 patients with atrial myxoma and 114 patients with atrial septal defect were collected from Mar 2012 to Aug 2015. 40 atrial myxoma and 77 atrial septal defect (ASD) patients underwent totally thoracoscopic surgery technique, while 24 atrial myxoma and 37 ASD patients underwent traditional median sternotomy. The baseline characteristics and perioperative data were recorded and analyzed from all cases. Follow-up data were obtained from outpatient clinics. RESULTS: All patients had successful resections or repairs. Compared with the traditional median sternotomy, the patients with atrial myxoma who underwent thoracoscopic surgery had longer operation time (208.08 ± 23.98 vs. 170.00 ± 16.58 min) while shorter intensive care unit (ICU) stay time (17.67 ± 4.95 vs. 49.88 ± 3.21 h), less blood drainage (127.87 ± 48.84 vs. 275.00 ± 59.01 ml) and shorter hospitalization days (9.97 ± 3.54 vs. 15.13 ± 1.06 days). For patients underwent ASD repair, longer operation time (232.92 ± 61.02 vs. 183.40 ± 54.63 min), shorter mechanical assistant ventilation time (4.82 ± 2.10 vs. 6.02 ± 2.50 h) and shorter ICU stay time (18.54 ± 5.80 vs. 39.68 ± 18.44 h) were detected in the thoracoscopic surgery group. There was no postoperative embolism events or death in all participated patients. Neither residual shunt nor atrioventricular blocks were detected in all ASD patients. CONCLUSIONS: Totally thoracoscopic surgery for atrial myxomas and atrial septal defect repair is more effective and safer. It provides another option to treat the patients with atrial myxoma and atrial septal defect.