Objective: Although the safety and efficacy of desvenlafaxine have been demonstrated, long-term evidence in Asians is lacking. We examined the safety and effectiveness of desvenlafaxine for up to 6 months in routine clinical practice in Korea. Methods: This multicenter, open-label, prospective observational study was conducted from February 2014 to February 2020 as a postmarketing surveillance study of desvenlafaxine (ClinicalTrials.gov identifier: NCT02548949). Adult patients with major depressive disorder (MDD) were observed from the initiation of treatment for 8 weeks (acute treatment phase) and then up to 6 months (continuation treatment phase) in a subsample. Safety was evaluated by incidence of adverse events (AE) and adverse drug reactions. Treatment response was assessed using the Clinical Global ImpressionImprovement (CGI-I) scale. Results: We included 700 and 236 study subjects in the analysis of acute and continuation treatment phase, respectively. In acute treatment phase, AE incidence was 9.86%, with nausea being most common (2.00%). In continuation treatment phase, AE incidence was 2.97%, with tremor occurring most frequently. After acute treatment (n = 464), the treatment response rate according to the CGI-I score at week 8 was 28.9%. In long-term users (n = 213), the response rate at month 6 was 45.5%. During the study period, no clinically relevant changes in BP were found regardless of concomitant use of antihypertensive drugs. Conclusion This study provides evidence on the safety and effectiveness of desvenlafaxine in adults with MDD, with a low incidence of AE, consistent AE profile with previous studies, and improved response after long-term treatment.

Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes.
Cardiovascular Diseases ; Cause of Death ; Cell Survival ; Cyclin E ; Cyclins ; Diabetic Cardiomyopathies ; Down-Regulation ; Glucose* ; Humans* ; Hyperglycemia ; Mitochondria ; Mitochondrial Dynamics* ; Stem Cells*

Endothelial progenitor cells (EPCs) are known to play an important role in the repair of damaged blood vessels. We used an endothelial progenitor cell colony-forming assay (EPC-CFA) to determine whether EPC numbers could be increased in healthy individuals through regular exercise training. The number of functional EPCs obtained from human peripheral blood-derived AC133 stem cells was measured after a 28-day regular exercise training program. The number of total endothelial progenitor cell colony-forming units (EPC-CFU) was significantly increased compared to that in the control group (p=0.02, n=5). In addition, we observed a significant decrease in homocysteine levels followed by an increase in the number of EPC-CFUs (p=0.04, n=5), indicating that the 28-day regular exercise training could increase the number of EPC colonies and decrease homocysteine levels. Moreover, an inverse correlation was observed between small-endothelial progenitor cell colony-forming units (small-EPC-CFUs) and plasma homocysteine levels in healthy men (r=-0.8125, p=0.047). We found that regular exercise training could increase the number of EPC-CFUs and decrease homocysteine levels, thus decreasing the cardiovascular disease risk in men.
Blood Vessels ; Cardiovascular Diseases ; Education ; Homocysteine* ; Humans ; Male ; Plasma ; Stem Cells*

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.
Anoxia ; Cell Movement ; Endothelial Cells ; Endothelial Progenitor Cells* ; Mitochondrial Dynamics* ; Oxygen ; RNA, Small Interfering