Selective PPARδ Agonist GW501516 Protects Against LPS-Induced Macrophage Inflammation and Acute Liver Failure in Mice via Suppressing Inflammatory Mediators.

Inflammation is critical in the development of acute liver failure (ALF). Peroxisome proliferator-activated receptor delta (PPARδ) regulates anti-inflammatory responses and is protective in several diseases such as obesity and cancer. However, the beneficial effects and underlying mechanisms of PPARδ agonist GW501516 in ALF remain unclear.

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases.

Positive Effect of Air Purifier Intervention on Baroreflex Sensitivity and Biomarkers of Oxidative Stress in Patients with Coronary Artery Disease: A Randomized Crossover Intervention Trial.

Exposure to fine particulate matter increases the risk of cardiovascular morbidity and mortality. Few studies have tested the beneficial effect of indoor air filtration intervention in patients with cardiovascular disease. The aim of this study is to investigate the effect of air filtration on mitigating cardiovascular health in patients with coronary artery disease.

Publication trends in South Korean research on particulate matter and health effects during two decades (2000-2019).

Ambient particulate matter is a serious risk factor for health outcomes associated with various diseases, including respiratory and cardiovascular diseases. South Korea is one of the Organization for Economic Cooperation and Development (OECD) countries with the highest concentration of ambient particulate matter. The purpose of this study is to identify the status of research on particulate matter and associated health effects in South Korea through bibliometric methods.

Age and Gender Effects on Genotoxicity in Diesel Exhaust Particles Exposed C57BL/6 Mice.

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM induced genomic damage. Here, we assessed the DNA damage potency of PM using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks.

Publication trends in research on particulate matter and health impact over a 10-year period: 2009-2018.

Exposure to ambient particulate matter is a major health risk factor for numerous diseases, including those of the cardiovascular and respiratory varieties. The aim of this study was to estimate the latest global research activities regarding particulate matter and health impact. We performed a bibliometric analysis of this field's scientific publication trends over a decade (2009-2018).

Coronin 1B regulates the TNFα-induced apoptosis of HUVECs by mediating the interaction between TRADD and FADD.

Coronin 1B is an actin-binding protein that plays important roles in actin-dependent cellular processes. We previously reported that coronin 1B is involved in vascular endothelial cell growth factor-induced migration of human umbilical vein endothelial cells (HUVECs). However, the role of coronin 1B in tumor necrosis factor alpha (TNFα)-induced endothelial cell apoptosis remained unknown.

Zileuton, a 5-Lipoxygenase Inhibitor, Exerts Anti-Angiogenic Effect by Inducing Apoptosis of HUVEC via BK Channel Activation.

The arachidonic acid metabolism through 5-lipoxygenase (5-LO) pathways is involved in modulating both tumorigenesis and angiogenesis. Although anti-carcinogenic activities of certain 5-LO inhibitors have been reported, the role of zileuton, a well known 5-LO inhibitor, on the endothelial cell proliferation and angiogenesis has not been fully elucidated. Here, we report that zileuton has an anti-angiogenic effect, and the underlying mechanisms involved activation of the large-conductance Ca-activated K (BK) channel.

Plasma ATG5 is increased in Alzheimer's disease.

Alzheimer's disease (AD) is a major cause of dementia. Growing evidence suggests that dysregulation of autophagy, a cellular mechanism essential for self-digestion of damaged proteins and organelles, is involved in neurological degenerative diseases including AD. Previously, we reported that autophagosomes are increased in the brains of AD mouse model.

Cigarette smoke extracts and cadmium induce COX-2 expression through γ-secretase-mediated p38 MAPK activation in C6 astroglia cells.

Exposure to cigarette smoke has been implicated in the progression of cerebrovascular and neurological disorders like stroke through inflammation and blood-brain barrier disruption. In this study, we investigated the signaling cascade activated by cigarette smoke extracts (CSE) and cadmium (Cd) resulting in the COX-2 induction in C6 rat astroglia cells. CSE or Cd induced Notch1 cleavage and activated p38 MAPK and CREB signaling pathways in C6 astroglia cells.

The Brain Donation Program in South Korea.

Purpose: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases.

Binding of coronin 1B to TβRI negatively regulates the TGFβ1 signaling pathway.

Coronin 1B is an actin-binding protein that regulates several actin-dependent cellular processes including migration and endocytosis. However, the role of coronin 1B in the tumor growth factor (TGF)β signaling pathway is largely unknown. Here, we investigated whether coronin 1B affects the TGFβ signaling cascade and found that coronin 1B negatively regulates the TGFβ signaling pathway.

Coronin 1B serine 2 phosphorylation by p38α is critical for vascular endothelial growth factor-induced migration of human umbilical vein endothelial cells.

Coronin 1B is an actin-binding protein that regulates various cellular processes including cell motility. However, the role of coronin 1B in vascular cell migration remains controversial. Here, we examined the function of coronin 1B in vascular endothelial growth factor (VEGF)-induced migration of human umbilical vein endothelial cells (HUVECs) and investigated the mechanism by which coronin 1B regulates this cellular process.

CaMKII-dependent myofilament Ca2+ desensitization contributes to the frequency-dependent acceleration of relaxation.

Background: Previous studies suggest that CaMKII activity is required for frequency-dependent acceleration of relaxation (FDAR) in ventricular myocytes. We propose that the underlying mechanism involves CaMKII-dependent regulation of myofilament Ca(2+) sensitivity.

Methods And Results: Cardiac function was measured in mice using murine echo machine.

Coronin 1A depletion protects endothelial cells from TNFα-induced apoptosis by modulating p38β expression and activation.

Coronins are conserved actin-binding proteins that regulate various cellular processes such as migration and endocytosis. Among coronin family members, coronin 1A is highly expressed in hematopoietic lineage cells where it regulates cell homeostasis. However, the expression and function of coronin 1A in endothelial cells have not yet been elucidated.

Stretch current-induced abnormal impulses in CaMKIIδ knockout mouse ventricular myocytes.

Background: CaMKII activation is proarrhythmic in heart failure where myocardium is stretched. However, the arrhythmogenic role of CaMKII in stretched ventricle has not been well understood.

Objective: We tested abnormal impulse inducibility by stretch current in myocytes isolated from CaMKIIδ knockout (KO) mouse left ventricle (LV) where CaMKII activity is reduced by ≈ 62%.

CaMKII inhibition in heart failure, beneficial, harmful, or both.

Calmodulin-dependent protein kinase II (CaMKII) has been proposed to be a therapeutic target for heart failure (HF). However, the cardiac effect of chronic CaMKII inhibition in HF has not been well understood. We have tested alterations of Ca(2+) handling, excitation-contraction coupling, and in vivo β-adrenergic regulation in pressure-overload HF mice with CaMKIIδ knockout (KO).

The PPARδ ligand L-165041 inhibits VEGF-induced angiogenesis, but the antiangiogenic effect is not related to PPARδ.

Peroxisome proliferator-activated receptor (PPAR)δ is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Recent studies have demonstrated that PPARδ is expressed in endothelial cells (ECs) and plays a potential role in endothelial survival and proliferation. Although PPARα and PPARγ are well recognized to play anti-inflammatory, antiproliferative, and antiangiogenic roles in ECs, the general effect of PPARδ on angiogenesis in ECs remains unclear.

HB-EGF induces cardiomyocyte hypertrophy via an ERK5-MEF2A-COX2 signaling pathway.

Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family that binds to and activates the EGF receptor. Transactivated by angiotensin II, ET-1, and various growth factors in cardiomyocytes, HB-EGF is known to induce cardiac hypertrophy via the PI3K-Akt, MAP kinase, and JAK-STAT pathways. However, little is known about the potential involvement of the ERK5 pathway in HB-EGF-induced cardiac hypertrophy.

Dynamic Kv4.3-CaMKII unit in heart: an intrinsic negative regulator for CaMKII activation.

Aims: Reduction of transient outward current (I(to)) and excessive activation of Ca(2+)/Calmodulin-dependent kinase II (CaMKII) are general features of ventricular myocytes in heart failure. We hypothesize that alterations of I(to) directly regulate CaMKII activation in cardiomyocytes.

Methods And Results: A dynamic coupling of I(to) channel subunit Kv4.

Alterations of L-type calcium current and cardiac function in CaMKII{delta} knockout mice.

Rationale: Recent studies have highlighted important roles of CaMKII in regulating Ca(2+) handling and excitation-contraction coupling. However, the cardiac effect of chronic CaMKII inhibition has not been well understood.

Objective: We have tested the alterations of L-type calcium current (I(Ca)) and cardiac function in CaMKIIdelta knockout (KO) mouse left ventricle (LV).

The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKC delta.

Zileuton has been demonstrated to act as an anti-inflammatory agent by virtue of its well-known ability to inhibit 5-lipoxygenase (5-LO). However, the effects of zileuton on cardiovascular disease and cardiomyocyte apoptosis are unclear. Here, we investigated the effects of zileuton on apoptosis of cardiac myogenic H9c2 cells and neonatal rat cardiomyocytes (NRCMs), and examined the possible role of PKC delta-mediated induction of COX-2 in these effects.

PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid accumulation and inflammation in LDLR-/- mice.

Although peroxisome proliferator-activated receptor delta (PPARdelta) has been implicated in energy metabolism and lipid oxidation process, detailed roles of PPARdelta in lipid homeostasis under pathologic conditions still remain controversial. Thus, we investigated the effect of PPARdelta ligand L-165041 on Western diet-induced fatty liver using low-density lipoprotein receptor-deficient (LDLR(-/-)) mice. LDLR(-/-) mice received either L-165041 (5mg/kg/day) or vehicle (0.