Peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily, are important in whole-body energy metabolism. PPARs are classified into three isoforms, namely, PPARα, β/δ, and γ. They are collectively involved in fatty acid oxidation, as well as glucose and lipid metabolism throughout the body. Importantly, the three isoforms of PPARs have complementary and distinct metabolic activities for energy balance at a cellular and whole-body level. PPARs also act with other co-regulators to maintain energy homeostasis. When endogenous ligands bind with these receptors, they regulate the transcription of genes involved in energy homeostasis. However, the exact molecular mechanism of PPARs in energy metabolism remains unclear. In this review, we summarize the importance of PPAR signals in multiple organs and focus on the pivotal roles of PPAR signals in cellular and whole-body energy homeostasis.

Cardiovascular diseases (CVDs) are a major cause of death worldwide. Due to the prevalence of many side effects and incomplete recovery from pharmacotherapies, stem cell therapy is being targeted for the treatment of CVDs. Among the different types of stem cells, endothelial progenitor cells (EPCs) have great potential. However, cellular replicative senescence decreases the proliferation, migration, and overall function of EPCs. Sirtuin 1 (SIRT1) has been mainly studied in the mammalian aging process. MHY2233 is a potent synthetic SIRT1 activator and a novel antiaging compound. We found that MHY2233 increased the expression of SIRT1, and its deacetylase activity thereby decreased expression of the cellular senescence biomarkers, p53, p16, and p21. In addition, MHY2233 decreased senescence-associated beta-galactosidase- (SA-β-gal-) positive cells and senescence-associated secretory phenotypes (SASPs), such as the secretion of interleukin- (IL-) 6, IL-8, IL-1α, and IL-1β. MHY2233 treatment protected senescent EPCs from oxidative stress by decreasing cellular reactive oxygen species (ROS) levels, thus enhancing cell survival and function. The angiogenesis, proliferation, and migration of senescent EPCs were enhanced by MHY2233 treatment. Thus, MHY2233 reduces replicative and oxidative stress-induced senescence in EPCs. Therefore, this novel antiaging compound MHY2233 might be considered a potent therapeutic agent for the treatment of age-associated CVDs.

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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.

Diabetic cardiomyopathy (DCM) is tightly linked to heart disorders and dysfunction or death of the cardiomyocytes including resident cardiac progenitor cells (CPCs) in diabetic patients. In order to restore loss of function of resident or transplanted CPCs, much research has focused on novel therapeutic strategies including the discovery of novel function-modulating factors such as reactive oxygen species (ROS) scavengers. Here, we developed and defined a novel antioxidant, MHY-1684, for enhancing the angiogenic potential of CPCs against ROS-related DCM. Short-term treatment with MHY-1684 restored ROS-induced CPC cell death. Importantly, MHY-1684 decreased hyperglycemia-induced mitochondrial ROS generation and attenuated hyperglycemia-induced mitochondrial fragmentation. We observed that the activation process of both Drp1 (phosphorylation at the site of Ser616) and Fis-1 is drastically attenuated when exposed to high concentrations of D-glucose with MHY-1684. Interestingly, phosphorylation of Drp1 at the site of Ser637, which is an inhibitory signal for mitochondrial fusion, is restored by MHY-1684 treatment, suggesting that this antioxidant may affect the activation and inhibition of mitochondrial dynamics-related signaling and mitochondrial function in response to ROS stress. In conclusion, our finding of the novel compound, MHY-1684, as an ROS scavenger, might provide an effective therapeutic strategy for CPC-based therapy against diabetic cardiomyopathy.

Background: Avipattikar churna, a poly-herbal formulation, is one of the popular ayurvedic formulations which is used for peptic ulcer diseases but the scientific documentation with regards to its effect for the indication is lacking. Aims:This study was carried out to evaluate the anti-secretory and the anti-ulcerogenic activities of the churna and to compare its activity with that of ranitidine in a pyloric ligated model of rats. Material and methods:Four groups of rats with 6 animals in each served as the ulcer controls, churna low dose (500 mg/ kg), churna high dose (750mg/kg) and ranitidine (25mg/kg). The control group rats received only vehicle (2% (v/v) gum acacia), while the rats of the other groups received the respective dose of the churna or ranitidine which was suspended in the vehicle. The treatments were given twice a day, orally, for two days. After 1 hour of the last dose, pyloric ligations were performed and the rats were sacrificed for evaluation after four hours of the ligations. The gastric contents were collected and its volume, pH and acidity were measured. The numbers of ulcers and their lengths were measured which were used to calculate the gastric irritancy index and the curative ratio. The histological examinations of the gastric tissues were also performed.

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Zika virus is an emerging arthropod borne virus (arbovirus) transmitted by Aedes (Stegomyia) mosquitoes. The virus belongs to the genus Flavivirus, family Flaviviridae, and is closely related to other Flavi viruses such as dengue, yellow fever and West Nile viruses. Zika Virus is an RNA virus containing 10,794 nucleotides encoding 3,419 amino acids. Zika Virus was first isolated from a rhesus monkey in the Zika Forest of Uganda, in 1947. 1 Zika Virus was first isolated from humans in 1968, in Nigeria. Zika Virus has been considered as emergent since 2007.In 2007, an outbreak of Zika Virus occurred on YAP, the western state of Micronesia. There was 49 conformed and 59 probable cases of Zika identified. Roughly 73% of the 11,241 population was infected according to the CDC. In November 2013, an outbreak occurred in the islands of Western Polynesia, including Tahiti. As of January 13, 2014 the number of confirmed Zika cases was 361, while the number of suspected cases was over 35,000. In February 2014, New Caledonia reported 49 cases, 30 were cases imported from French Polynesia, some cases were confirmed to be autochthonous. 2 Clinical Manifestations: The first well-documented report of human Zika Virus disease was in 1964 when Simpson described his own occupationally acquired Zika illness at age 28. It began with mild headache. Next day, a maculopapular rash covered his face, neck, trunk, and upper arms, and spread to his palms and soles. Transient fever, malaise, and back pain developed. By the evening of the second day of illness he was a febrile, the rash was fading, and he felt better. By day three, he felt well and had only the rash, which disappeared over the next 2 days. Zika Virus was isolated from serum collected while he was febrile. 3 In 1973, laboratory-acquired Zika Virus illness in a man was reported with acute onset of fever, headache, and joint pain but no rash which was isolated from serum collected on the first day of symptoms; the man's illness resolved in 1 week. Of the 7 Zika Virus case-patients in Indonesia, all had fever, but they were detected by hospital-based surveillance for febrile illness. 4 Other manifestations included anorexia, diarrhea, constipation, abdominal pain, and dizziness. The outbreak on Yap Island was characterized by rash, conjunctivitis, and ABSTRACT Zika virus, a mosquito borne flavivirus transmitted primarily by Aedes aegypti mosquitoes is a pathogen affecting humans. These vectors also transmit dengue and chikungunya virus and are found throughout much of the world, including parts of the United States. An estimated 80% of persons infected with Zika virus are asymptomatic. Microcephaly is the greater risk for the infant born from the Zika Virus infected pregnant mother. This virus also causes neurological syndromes. Zika virus disease can often be diagnosed by performing reverse transcriptase-polymerase chain reaction (RT-PCR) on serum.