ABSTRACT
ObjectiveTo investigate the effect and underlying molecular mechanism of astragaloside-Ⅳ （AS-Ⅳ） on autophagy and apoptosis of nasopharyngeal carcinoma cells. MethodIn experiments in vitro， the effect of AS-Ⅳ on the autophagy of nasopharyngeal carcinoma cells was observed by monodansylcadaverine （MDC） staining and transmission electron microscopy （TEM）. In experiments in vivo， immunofluorescence （IF） and Western blot were used to detect the changes in autophagy and apoptosis and the expression of key proteins in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway after the establishment of a xenograft tumor model in nude mice. ResultAfter 5-8F cells were treated with AS-Ⅳ of different doses （5， 10， 20 μmol·L-1）， the fluorescence intensity of autophagy in AS-Ⅳ groups significantly increased as compared with that in the blank group. The fluorescence expression of autophagy in AS-Ⅳ groups was the strongest after intervention for 24 hours， and the fluorescence expression in the 10 μmol·L-1 AS-Ⅳ group was the most obvious. The autophagy activator rapamycin （RAPA） induced more autophagosomes in 5-8F cells under the transmission electron microscope， and 3-methyladenine （3-MA）， an autophagy inhibitor， did not induce autophagosome formation in 5-8F cells under the transmission electron microscope as compared with the results in the blank group. In the 10 μmol·L-1 AS-Ⅳ group， the intracellular structure and cell membrane were intact and clear， and autophagosome formation was observed. Compared with the blank group， the AS-Ⅳ groups showed inhibited tumor volume （P<0.05， P<0.01）， potentiated fluorescence signals of microtubule-associated protein l light chain 3 type Ⅱ/microtubule-associated protein l light chain 3 type Ⅰ （LC3 Ⅱ/Ⅰ） and cleaved Caspase-3 （P<0.05， P<0.01）， increased expression levels of the mammalian homolog of yeast ATG6 （Beclin-1）， LC3 Ⅱ/Ⅰ， cleaved Caspase-3， and cleaved PARP （P<0.05， P<0.01）， down-regulated expression of ubiquitin-binding protein （p62） （P<0.05， P<0.01）， and reduced protein expression levels of phosphorylated PI3K （p-PI3K）， phosphorylated Akt （p-Akt）， and phosphorylated mTOR （p-mTOR） （P<0.05， P<0.01）. ConclusionAS-Ⅳ can induce autophagy and apoptosis of nasopharyngeal carcinoma cells， and the mechanism is presumably attributed to the activation of the PI3K/Akt/mTOR signaling pathway.
ABSTRACT
Cisplatin is a broad-spectrum and highly effective chemotherapeutic agent, with a dose-dependent therapeutic effect.Unfortunately, high-does therapy is limited by ototoxicity, nephrotoxicity and neurotoxicity.Ototoxicity is a common and serious complication after cisplatin chemotherapy, which has greatly debilitating effect on patients′ quality of life.Currently, there are no FDA-approved drugs available to prevent cisplatin-induced hearing loss.In recent years, domestic and international studies on cisplatin-induced ototoxicity have revealed many new mechanisms and therapeutic targets.Many candidate agents have shown good hearing protection.Moreover, local drug delivery methods are being optimized, promising for further translations to clinical applications.
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Objective:To evaluate the mid-term follow-up results of arteriovenous graft(AVG) for patients on maintenance hemodialysis.Methods:The clinical data of 131 patients who implanted AVG from Jan 2014 to Dec 2016 at Department of Vascular Surgery, Nanfang Hospital, Southern Medical University were retrospectively analyzed.Results:The mean follow-up time was 22.8 months (ranging from 2 to 61 months). The average primary patency time after AVG was (22.20±1.97) months, and the primary patency rates at 1 year, 2 years, 3 years were 61.5%, 36.6% and 23.2%, respectively. The average secondary patency time after AVG was (38.30±2.30) months, and the secondary patency rates after 1 year, 2 years, 3 years were 85.6%, 68.6%, and 55.8%, respectively. Sixty five (49.6%) patients had thrombosis after operations, 50(38.2%) had access stenosis, 13(9.9%) had graft infections, and 2(1.5%) had pseudoaneurysm, 2(1.5%) had hemodialysis access-induced distal ischemia, 2(1.5%) had seroma.Conclusions:Though the primary patency rate of AVG is worse than that of arteriovenous fistula (AVF), a satisfactory secondary patency rate can be achieved through repair treatments. Regular follow-up, early detection of stenotic lesions and treatments are vital for long-term patency of AVG.
ABSTRACT
[Summary] To investigate the effect of microRNA126 on glucose metabolism in the normal liver cell lines. In vitro, the chang liver cell lines were cultured. Under the most effective transfection conditions ascertained above, microRNA126 mimic, microRNA126 inhibitor, and relative negative control were transfected into the cultured normal liver cells. And the transfection efficiency was tested by realtime fluorescent quantitative PCR. After 48 hours, the cells were stimulated with synthetic insulin ( 100 nmol/L ) and respective substrates for 2 hours. Then the glycogenesis, gluconeogenesis, and glycolysis in cells were measured. The level of microRNA126 of the microRNA126 mimic group was higher than the other groups, and the difference was statistically significant ( P<0. 05 ). MicroRNA126 mimic group significantly decreased glucose utilization, reduced glycogen synthesis, effectively increased the account of gluconeogenesis, reduced lactate production, and pyruvate kinase activity ( all P<0. 05). The over-expressing microRNA126 in hepatocytes may reverse the function of glucose metabolism, and enhance output of hepatic glucose.