Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

Background@#We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. @*Methods@#Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. @*Results@#G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. @*Conclusion@#Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

Role of MicroRNA-34a in Anti-Apoptotic Effects of Granulocyte-Colony Stimulating Factor in Diabetic Cardiomyopathy

BACKGROUND: Recent studies have shown that microRNAs (miRNAs) are involved in the process of cardiomyocyte apoptosis. We have previously reported that granulocyte-colony stimulating factor (G-CSF) ameliorated diastolic dysfunction and attenuated cardiomyocyte apoptosis in a rat model of diabetic cardiomyopathy. In this study, we hypothesized a regulatory role of cardiac miRNAs in the mechanism of the anti-apoptotic effect of G-CSF in a diabetic cardiomyopathy rat model.METHODS: Rats were given a high-fat diet and low-dose streptozotocin injection and then randomly allocated to receive treatment with either G-CSF or saline. H9c2 rat cardiomyocytes were cultured under a high glucose (HG) condition to induce diabetic cardiomyopathy in vitro. We examined the extent of apoptosis, miRNA expression, and miRNA target genes in the myocardium and H9c2 cells.RESULTS: G-CSF treatment significantly decreased apoptosis and reduced miR-34a expression in diabetic myocardium and H9c2 cells under the HG condition. G-CSF treatment also significantly increased B-cell lymphoma 2 (Bcl-2) protein expression as a target for miR-34a. In addition, transfection with an miR-34a mimic significantly increased apoptosis and decreased Bcl-2 luciferase activity in H9c2 cells.CONCLUSION: Our results indicate that G-CSF might have an anti-apoptotic effect through down-regulation of miR-34a in a diabetic cardiomyopathy rat model.

Percutaneous radiologic gastrostomy in patients with failed percutaneous endoscopic gastrostomy

BACKGROUND: To determine the technical feasibility and success rate of percutaneous radiologic gastrostomy (PRG) after failure of percutaneous endoscopic gastrostomy (PEG). METHODS: Consecutive patients referred for PRG after failure of PEG between May 2011 and June 2016 were included in this study. The reasons for the failure of PEG, as well as the technical success and complications of PRG were noted. RESULTS: Fifteen patients (14 men, 1 woman; age, 27-93 years) were included. The most common reasons for PEG failure were esophageal stricture due to malignancies (n = 8), unfavorable abdominal wall conditions (n = 3), unstable patient condition during endoscopy (n = 2), and other miscellaneous conditions (n = 2). PRG placement was technically successful in all 15 cases. In one case, early slip-out of the gastrostomy tube occurred, which required removal and repositioning. No mortality was noted. CONCLUSION: PRG is technically feasible in patients with failed PEG insertion, and has advantages over PEG and a high overall success rate.

Signet-ring cell carcinoma of the appendix: a case report with an emphasis on sonographic findings

In this report, we present a rare case of primary signet-ring cell carcinoma of the appendix in a 51-year-old woman with right lower quadrant pain. Since non-specific concentric appendiceal wall thickening was found in a radiologic evaluation, it was misdiagnosed as non-tumorous appendicitis. An in-depth examination of the correlation between sonographic and histopathologic findings demonstrated that a single markedly thickened hypoechoic layer was well correlated with the diffuse infiltration of tumor cells in both the submucosal and muscle layers. If this sonographic finding is observed in certain clinical settings, such as potential ovarian and peritoneal metastasis, submucosal infiltrative tumors, including signet-ring cell carcinoma, should be considered in the differential diagnosis.

Supradiaphragmatic Liver Confirmed by a Hepatocyte-specific Contrast Agent (Gd-EOB-DTPA): A Case Report

Supradiaphragmatic liver is a rare condition. Establishing an accurate preoperative diagnosis is difficult. Operative exploration is necessary to differentiate this lesion from intrathoracic masses, such as a pleural based tumor, diaphragmatic tumor and peripheral lung tumor. However, with the aid of the hepatocyte-specific magnetic resonance imaging contrast agent, gadoxetic acid (Gd-EOB-DTPA), functional hepatocytes in the lesion can be identified in the hepatobiliary phase, potentially allowing an accurate and non-invasive diagnosis. We report a case of supradiaphragmatic liver diagnosed by Gd-EOB-DTPA-enhanced magnetic resonance imaging.