Peroxisome proliferator-activated receptor-δ-mediated upregulation of catalase helps to reduce ultraviolet B-induced cellular injury in dermal fibroblasts.

Background: Previous studies suggested that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-δ plays an essential role in cellular responses against oxidative stress.

Objective: To investigate how PPAR-δ elicits cellular responses against oxidative stress in primary human dermal fibroblasts (HDFs) exposed to ultraviolet B (UVB).

Methods: The present study was undertaken in HDFs by performing real-time polymerase chain reaction, gene silencing, cytotoxicity and reporter gene assay, analyses for catalase and reactive oxygen species, and immunoblot analyses.

Cost-effectiveness of a national immunization program with the 13-valent pneumococcal conjugate vaccine compared with the 10-valent pneumococcal conjugate vaccine in South Korea.

Introduction: Globally, pneumococcal disease represents a significant burden. South Korea implemented the 7-valent pneumococcal conjugate vaccine (PCV7) in 2003, replaced with the 10-valent (PCV10) and 13-valent (PCV13) vaccine in 2010. In 2014, both vaccines were introduced in the national immunization program (NIP) for infants with 3 primary doses and one booster dose We performed a cost-effectiveness evaluation to elucidate which vaccine may be expected to provide greater impact if included in a NIP.

Duck Oil-loaded Nanoemulsion Inhibits Senescence of Angiotensin II-treated Vascular Smooth Muscle Cells by Upregulating SIRT1.

Cellular senescence is associated with age-related vascular disorders and has been implicated in vascular dysfunctions. Here, we show that duck oil-loaded nanoemulsion (DO-NE) attenuates premature senescence of vascular smooth muscle cells (VSMCs) triggered by angiotensin II (Ang II). Compared with control nanoemulsion (NE), DO-NE significantly inhibited the activity of senescence-associated β-galactosidase, which is a biomarker of cellular senescence, in Ang II-treated VSMCs.

Comparative effects of nanoemulsions loaded with duck oil and lard oil on palmitate-induced lipotoxicity.

The effects of duck oil and lard oil on lipotoxicity induced by saturated long-chain fatty acids were evaluated in HepG2 cells. Lipotoxicity triggered by palmitate, a saturated fatty acid, was inhibited more by duck oil-loaded nanoemulsion (DO-NE) than by lard oil-loaded nanoemulsion (LO-NE) and control nanoemulsion (NE) in HepG2 cells. Accumulation of reactive oxygen species and lipid vacuoles in HepG2 cells induced by palmitate treatment was inhibited by DO-NE but not by LO-NE.

Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS.

We investigated the effect of peroxisome proliferator-activated receptor δ (PPARδ) on angiotensin II (Ang II)-triggered hypertrophy of vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand of PPARδ, significantly inhibited Ang II-stimulated protein synthesis in a concentration-dependent manner, as determined by [3H]-leucine incorporation. GW501516-activated PPARδ also suppressed Ang II-induced generation of reactive oxygen species (ROS) in VSMCs.

Nanoemulsions improve the efficacy of turmeric in palmitate- and high fat diet-induced cellular and animal models.

Turmeric is a well-known functional food exhibiting multiple biological activities in health and disease. However, low aqueous solubility and poor bioavailability limit its therapeutic potential. Herein, we investigated the utility of nanoemulsions as a carrier to improve the efficacy of turmeric.

Formononetin inhibits lipopolysaccharide-induced release of high mobility group box 1 by upregulating SIRT1 in a PPARδ-dependent manner.

Background: The release of high mobility group box 1 (HMGB1) induced by inflammatory signals acts as a cellular alarmin to trigger a chain of inflammatory responses. Although the inflammatory actions of HMGB1 are well studied, less is known about the therapeutic agents that can impede its release. This study investigated whether the isoflavonoid formononetin can modulate HMGB1 release in cellular inflammatory responses.

The viability of primary hepatocytes is maintained under a low cysteine-glutathione redox state with a marked elevation in ophthalmic acid production.

Extracellular cystine, the oxidized form of cysteine (Cys), is taken up by cells via the cystine transporter xCT. xCT is not expressed in the liver but is induced in primary hepatocytes under conventional cultured conditions. However, compared to wild-type hepatocytes those from the xCT-knockout mouse showed no evidence of an abnormality and the levels of both Cys and glutathione (GSH) remained unchanged.

xCT deficiency aggravates acetaminophen-induced hepatotoxicity under inhibition of the transsulfuration pathway.

Cystine, an oxidized form of cysteine (Cys), is imported into cells via the protein xCT, which is also associated with the export of glutamate as the counter amino acid. In the current study, we attempted to rationalize roles of xCT in the livers of male mice. While xCT was not expressed in the livers of ordinary mice, it was induced under conditions of glutathione depletion, caused by the administration of acetaminophen (AAP).

Ascorbic acid prevents acetaminophen-induced hepatotoxicity in mice by ameliorating glutathione recovery and autophagy.

Aldehyde reductase (AKR1A) plays a role in the biosynthesis of ascorbic acid (AsA), and AKR1A-deficient mice produce about 10-15% of the AsA that is produced by wild-type mice. We found that acetaminophen (AAP) hepatotoxicity was aggravated in AKR1A-deficient mice. The pre-administration of AsA in the drinking water markedly ameliorated the AAP hepatotoxicity in the AKR1A-deficient mice.

SOD1 deficiency decreases proteasomal function, leading to the accumulation of ubiquitinated proteins in erythrocytes.

We previously demonstrated that elevated levels of ROS in red blood cells (RBCs) are responsible for anemia in SOD1-deficient mice, suggesting that the oxidative stress-induced massive destruction of RBCs is an underlying mechanism for autoimmune hemolytic anemia. In the current study, we examined the issue of how elevated ROS are involved in the destruction of RBCs and the onset of anemia from the view point of the proteolytic removal of oxidatively-damaged proteins. We found that poly-ubiquitinated proteins had accumulated and had undergone aggregation in RBCs from SOD1-deficient mice and from phenylhydrazine-induced anemic mice.

Oxidative stress triggers lipid droplet accumulation in primary cultured hepatocytes by activating fatty acid synthesis.

Despite the impaired intestinal lipid absorption and low level of visceral fat, the Sod1-deficient mouse is susceptible to developing liver steatosis. To gain insights into the mechanism responsible for this abnormal lipid metabolism, we analyzed primary cultured hepatocytes obtained from Sod1-deficient and wild-type mice. Lipid droplets began to accumulate in the cultured hepatocytes and was further increased by a Sod1 deficiency.

SOD1 deficiency induces the systemic hyperoxidation of peroxiredoxin in the mouse.

A deficiency of superoxide dismutase 1 (SOD1) or peroxiredoxin (Prx) 2 causes anemia in mice due to elevated oxidative stress. In the current study, we investigated whether intrinsic oxidative stress caused by a SOD1 deficiency affected the redox status of Prx2 and other isoforms in red blood cells (RBCs) and several organs of mice. We observed a marked elevation in hyperoxidized Prx2 levels in RBCs from SOD1-deficient mice.

Dalbergia odorifera Extract Ameliorates UVB-Induced Wrinkle Formation by Modulating Expression of Extracellular Matrix Proteins.

Preclinical Research Emerging evidence suggests that Dalbergia odorifera T. Chen (Leguminosae), an indigenous medicinal herb, has therapeutic potential. This study examined the antiwrinkle effects of ethanol extracts of D.

From lignocellulosic biomass to furans via 5-acetoxymethylfurfural as an alternative to 5-hydroxymethylfurfural.

A facile pathway to furan derivatives from lignocellulosic biomass via 5-acetoxymethylfurfural (AMF) was developed. AMF possesses advantageous properties due to its less-hydrophilic acetoxymethyl group relative to the hydroxymethyl group of 5-hydroxymethylfurfural (HMF). The hydrophobicity and chemical stability of AMF allowed practical isolation and purification to afford a highly pure product of up to 99.

Ethanol extract of Dalbergia odorifera protects skin keratinocytes against ultraviolet B-induced photoaging by suppressing production of reactive oxygen species.

Dalbergia odorifera T. Chen (Leguminosae), an indigenous medicinal herb, has been widely used in northern and eastern Asia to treat diverse diseases. Here, we investigated the anti-senescent effects of ethanolic extracts of Dalbergia odorifera (EEDO) in ultraviolet (UV) B-irradiated skin cells.

Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression.

Peroxisome proliferator-activated receptor (PPAR) δ is implicated in the carcinogenesis of several types of cancer. However, the therapeutic efficacy of PPARδ ligands against cancer progression is unclear. Here, we showed that PPARδ modulates the migration and invasion of melanoma cells by up-regulating Snail expression.

Peroxisome proliferator-activated receptor δ modulates MMP-2 secretion and elastin expression in human dermal fibroblasts exposed to ultraviolet B radiation.

Background: Changes in skin connective tissues mediated by ultraviolet (UV) radiation have been suggested to cause the skin wrinkling normally associated with premature aging of the skin. Recent investigations have shown that peroxisome proliferator-activated receptor (PPAR) δ plays multiple biological roles in skin homeostasis.

Objective: We attempted to investigate whether PPARδ modulates elastin protein levels and secretion of matrix metalloproteinase (MMP)-2 in UVB-irradiated human dermal fibroblasts (HDFs) and mouse skin.

Activation of peroxisome proliferator-activated receptor δ inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells.

We investigated the role of peroxisome proliferator-activated receptor (PPAR) δ on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARδ by GW501516, a specific ligand for PPARδ, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II.

PPARδ reduces abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice by regulating extracellular matrix homeostasis and inflammatory responses.

Background: Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by a localized degradation of connective tissue and apoptosis of vascular smooth muscle cells. This study examined whether the ligand-activated peroxisome proliferator-activated receptor (PPAR) δ can directly antagonize angiotensin II (Ang II)-induced AAA formation in apoE-deficient mice.

Methods And Results: Six-month-old male apoE-deficient mice were infused with Ang II and/or GW501516 (1.

Activation of peroxisome proliferator-activated receptor γ by rosiglitazone inhibits lipopolysaccharide-induced release of high mobility group box 1.

Peroxisome proliferator-activated receptors (PPARs) are shown to modulate the pathological status of sepsis by regulating the release of high mobility group box 1 (HMGB1), a well-known late proinflammatory mediator of sepsis. Ligand-activated PPARs markedly inhibited lipopolysaccharide- (LPS) induced release of HMGB1 in RAW 264.7 cells.

The PPARδ-mediated inhibition of angiotensin II-induced premature senescence in human endothelial cells is SIRT1-dependent.

Cellular senescence has been implicated in endothelial dysfunctions affecting vascular tone and regeneration. The molecular mechanisms of vascular senescence are poorly understood. The present study demonstrates that upregulation of SIRT1 by peroxisome proliferator-activated receptor (PPAR) δ attenuates premature senescence in angiotensin (Ang) II-treated human coronary artery endothelial cells (HCAECs).

Antioxidative effects of Alisma orientale extract in palmitate-induced cellular injury.

Context: Alisma orientale (Sam.) Juzepczuk (Alismataceae) is an indigenous medicinal herb that has been traditionally used for diuretic, hypolipidemic, anti-inflammatory, and antidiabetic proposes in northern and eastern Asia.

Objective: This study examined the mechanisms underlying the cytoprotective effect of an aqueous extract of A.

Activation of PPARδ counteracts angiotensin II-induced ROS generation by inhibiting rac1 translocation in vascular smooth muscle cells.

Angiotensin II (Ang II)-mediated modification of the redox milieu of vascular smooth muscle cells (VSMCs) has been implicated in several pathophysiological processes, including cell proliferation, migration and differentiation. In this study, we demonstrate that the peroxisome proliferator-activated receptor (PPAR) δ counteracts Ang II-induced production of reactive oxygen species (ROS) in VSMCs. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly reduced Ang II-induced ROS generation in VSMCs.