ABSTRACT
Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.
ABSTRACT
Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.
ABSTRACT
Malaria, tuberculosis, and hepatitis are common and notorious infectious diseases in Myanmar. Despite intensive efforts to control these diseases, their prevalence remains high. For malaria, which is a vector-borne disease, a remarkable success in the reduction of new cases has been achieved. However, the annual number of tuberculosis cases has increased over the last few decades, and the prevalence of chronic viral hepatitis infection has been high in Myanmar and other nearby countries. Early detection and prompt treatment are crucial to control these diseases. We have devoted our research efforts to understanding the status of these infectious diseases and working towards their eventual elimination for the last four years with the support of the Korea International Cooperation Agency. In the modern era, an infection that develops in one geographical area can spread globally because national borders do not effectively limit disease transmission. Our efforts to understand the status of infectious diseases in Myanmar will benefit not only Myanmar but also neighboring countries such as Korea.
Subject(s)
Communicable Diseases , Hepatitis , International Cooperation , Korea , Malaria , Myanmar , Prevalence , TuberculosisABSTRACT
BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine fulfilling a broad variety of immunoregulatory functions. Monocytes and macrophages play a pivotal role in inflammation and immune regulation. NF-kappaB and HIF-1 are known to increase expression of the TNF-alpha gene in a separate way. METHODS: Human monocytic leukemia, U937 cells, were transfected using the standard electroporation method for intracellular expression of NF-kappaB and HIF-1. We performed analysis using the mammalian two-hybrid assay and co-immunoprecipitation assay for detection of protein interaction of both proteins. In addition, chromatin immunoprecipitation analysis was performed for examination of NF-kappaB and HIF-1 binding on the TNF-alpha gene promoter. RESULTS: Here we show that NF-kappaB and HIF-1 cooperatively induced an increase in expression of the TNF-alpha gene dependent on promoter activity by the direct protein interaction of these two transcription factors. Hypoxia signaling induced marked enhancement of the transactivation of TNF-alpha promoter by HIF-1 and NF-kappaB. A tandem NF-kappaB/HIF-1 binding site was identified within the TNF-alpha promoter, which acted as a strong enhancer element. Physical association of the Rel domain of NF-kappaB and the N-TD domain of HIF-1 was required. Hypoxia treatment also resulted in a significant increase in the protein interaction of NF-kappaB and HIF-1 in vivo. Both transcription factors were recruited on the chromatin TNF-alpha promoter dependent on hypoxia stimuli. CONCLUSION: The results of this study indicate that a variety of extracellular signals for activation of TNF-alpha gene expression might converge on the transcriptional regulation through the NF-kappaB/HIF-1 signaling pathway.
Subject(s)
Humans , Hypoxia , Binding Sites , Chromatin , Chromatin Immunoprecipitation , Electroporation , Enhancer Elements, Genetic , Gene Expression , Immunoprecipitation , Inflammation , Leukemia , Macrophages , Monocytes , NF-kappa B , Proteins , Transcription Factors , Transcriptional Activation , Tumor Necrosis Factor-alpha , Two-Hybrid System Techniques , U937 CellsABSTRACT
No abstract available.