VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance.

Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and RhoGDI2 expression is positively correlated with VEGF-C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo. Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2-overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer.

Anti-obesity Activity of Ethanol Extract from Bitter Melon in Mice Fed High-Fat Diet.

In many cases, obesity is associated with metabolic disorders. Recently, natural compounds that may be beneficial for improving obesity have received increasing attention. Bitter melon has received attention as a diabetes treatment. NAD+-dependent deacetylase (Sirtuin 1, SIRT1) has emerged as a novel therapeutic target for metabolic diseases. In this study, ethanol extract of bitter melon (BME) suppressed adipocyte differentiation and significantly increased the expression of SIRT1 in fully differentiated 3T3-L1 cells. Moreover, it enhanced the activation of AMP-activated protein kinase (AMPK). In high-fat diet (HFD)-fed induced-obesity mice, BME suppressed HFD-induced increases in body weight and white adipose tissue (WAT) weight. BME also increased the expression of SIRT1 and suppressed peroxisome proliferator-activated receptor and sterol regulatory element binding protein 1 expressions of WAT from HFD-fed mice. These findings suggest that BME prevents obesity by activating the SIRT1 and AMPK pathway and that it may be a useful dietary supplement for preventing obesity.

Successful Conservative Management of Tracheal Injury After Forceful Coughing During Extubation: A Case Report.

A-56-year-old woman underwent carpal tunnel release surgery under general anesthesia. Thirty minutes after extubation, the patient complained of chest discomfort with dyspnea. Swelling of the neck and upper anterior chest was observed. Computed tomography of the chest showed tracheal rupture at the brachiocephalic trunk level, and bronchoscopy demonstrated a 5 cm linear tracheal defect in the posterior membranous wall, 6 cm proximal to the carina. Surgical repair of the tracheal injury was impossible due to its location. The patient was managed with intubation, mechanical ventilator care, and antibiotics. She made a full and uncomplicated recovery and was discharged 18 days after the original injury. When suspicious symptoms appear in patients receiving mechanical ventilation support, an immediate and accurate diagnostic process should be undertaken to rule out endotracheal tube-related tracheal injuries and to avoid potentially lethal complications.

Betaxolol, a beta1-adrenoceptor antagonist, protects a transient ischemic injury of the retina.

In the present study, we investigated the protective effects of the topical beta-adrenoceptor antagonist Betoptic((R)) (0.25% betaxolol) in the rat retina following the ischemic injury induced by a transient increase of intraocular pressure (IOP). Like other areas of the central nervous system, the retina is highly vulnerable to ischemic-induced injury. Ischemia was induced in the rat retina by raising the IOP above the systolic blood pressure for 60min. After an ischemia/reperfusion, the thickness of the retinal layers and the immunoreactivities of choline acetyltransferase (ChAT), gamma-amino butyric acid (GABA) and tyrosine hydroxylase (TH) were examined. After a reperfusion period of 7 days, the thickness of both the inner plexiform layer and inner nuclear layer was much decreased. After a reperfusion period of 14-28 days, the thickness of the outer nuclear layer decreased markedly. Moreover, the ChAT and TH immunoreactivity had almost completely disappeared in the retinas after 7 days, while GABA immunoreactivity remained for 28 days. These results suggest that the inner retinal layers are more susceptible to ischemic-induced injury than the outer retinal layer.Histological examination demonstrated protective effects of betaxolol on ischemic-induced retinal damage, which was more substantial in the inner retinal layer. When two drops of betaxolol, once before ischemic injury and twice daily for 28 days after ischemia, were continuously administered, the reductions in the retinal ChAT, GABA and TH immunoreactivities were significantly attenuated. The present study suggests that topically applied betaxolol is an efficient neuroprotective agent and prevents the retinal cell damage induced by ischemic injury in rats.