Clinical risk factors associated with the development of wheezing in children less than 2 years of age who required hospitalization for viral lower respiratory tract infections

PurposeWheezing following viral lower respiratory tract infections (LRTIs) in children <2 years of age is an important risk factor for the development of asthma later in life; however, not all children with viral LRTIs develop wheezing. This study investigated risk factors for the development of wheezing during viral LRTIs requiring hospitalization.MethodsThe study included 142 children <2 years of age hospitalized for LRTIs with at least one virus identified as the cause and classified them into children diagnosed with LRTIs with wheezing (n=70) and those diagnosed with LRTIs without wheezing (n=72).ResultsThere were no significant differences in the viruses detected between the two groups. Multivariate logistic regression analysis showed that, after adjusting for potentially confounding variables including sex and age, the development of wheezing was strongly associated with parental history of allergic diseases (adjusted odds ratio [aOR], 20.19; 95% confidence interval [CI], 3.22-126.48), past history of allergic diseases (aOR, 13.95; 95% CI, 1.34-145.06), past history of hospitalization for respiratory illnesses (aOR, 21.36; 95% CI, 3.77-120.88), exposure to secondhand smoke at home (aOR, 14.45; 95% CI, 4.74-44.07), and total eosinophil count (aOR, 1.01; 95% CI, 1.01-1.02).ConclusionPast and parental history of allergic diseases, past history of hospitalization for respiratory illnesses, exposure to secondhand smoke at home, and total eosinophil count were closely associated with the development of wheezing in children <2 years of age who required hospitalization for viral LRTIs. Clinicians should take these factors into consideration when treating, counseling, and monitoring young children admitted for viral LRTIs

Original Article Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells

Abstract: STAT3 has been recognized as an efficacious drug target for prostate cancer because of its constitutive activation in this fatal disease. We recently identified the root bark of Morus alba Linn. as a potential STAT3 inhibitor among 33 phytomedicines traditionally used in Korea. Morusin, an active compound isolated from the root bark of Morus alba, has shown anti-oxidant and anti-inflammatory effects. In the present study, we examined whether morusin has a potential as an anti-cancer agent in prostate cancer. We found that morusin suppressed viability of prostate cancer cells, but little effect in normal human prostate epithelial cells. Morusin also reduced STAT3 activity by inhibiting its phosphorylation, nuclear accumulation, and DNA binding activity. In addition, morusin down-regulated expression of STAT3 target genes encoding Bcl-xL, Bcl-2, Survivin, c-Myc and Cyclin D1, which are involved in regulation of apoptosis and cell cycle. Furthermore, morusin induced apoptosis in human prostate cancer cells by reducing STAT3 activity. Taken together, these results suggest that morusin could be a potentially therapeutic agent for prostate cancer by reducing STAT3 activity and inducing apoptosis

Eckol Enhances Heme Oxygenase-1 Expression through Activation of Nrf2/JNK Pathway in HepG2 Cells

Eckol isolated from Ecklonia stolonifera was previously reported to exhibit cytoprotective activity with its intrinsic antioxidant activity in in vitro studies. In this study, we characterized the mechanism underlying the eckol-mediated the expression of heme oxygenase-1 (HO-1). Eckol suppressed the production of intracellular reactive oxygen species and increased glutathione level in HepG2 cells. Eckol treatment enhanced the expression of HO-1 at the both level of protein and mRNA in HepG2 cells. Enhanced expression of HO-1 by eckol was presumed to be the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2) demonstrated by its nuclear translocation and increased transcriptional activity. c-Jun NH2-terminal kinases (JNKs) and PI3K/Akt contributed to Nrf2-mediated HO-1 expression. These results demonstrate that the eckol-mediated expression of HO-1 in HepG2 cells is regulated by Nrf2 activation via JNK and PI3K/Akt signaling pathways, suggesting that eckol may be used as a natural antioxidant and cytoprotective agent

Dieckol Ameliorates Aβ Production via PI3K/Akt/GSK-3β Regulated APP Processing in SweAPP N2a Cell

The proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase releases amyloid-β peptide (Aβ), which deposits in amyloid plaques and contributes to the initial causative events of Alzheimer’s disease (AD). In the present study, the regulatory mechanism of APP processing of three phlorotannins was elucidated in Swedish mutant APP overexpressed N2a (SweAPP N2a) cells. Among the tested compounds, dieckol exhibited the highest inhibitory effect on both intra- and extracellular Aβ accumulation. In addition, dieckol regulated the APP processing enzymes, such as α-secretase (ADAM10), β-secretase, and γ-secretase, presenilin-1 (PS1), and their proteolytic products, sAPPα and sAPPβ, implying that the compound acts on both the amyloidogenic and non-amyloidogenic pathways. In addition, dieckol increased the phosphorylation of protein kinase B (Akt) at Ser473 and GSK-3β at Ser9, suggesting dieckol induced the activation of Akt, which phosphorylated GSK-3β. The specific phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 triggered GSK-3β activation and Aβ expression. In addition, co-treatment with LY294002 noticeably blocked the effect of dieckol on Aβ production, demonstrating that dieckol promoted the PI3K/Akt signaling pathway, which in turn inactivated GSK-3β, resulting in the reduction in Aβ levels

Anti-inflammatory effect of ethanolic extract from <it>Myagropsis myagroides</it> on murine macrophages and mouse ear edema

Abstract Background This study aims to investigate anti-inflammatory effect of ethanolic extract of Myagropsis myagroides (EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms. Methods The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance. Results EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-κB by preventing degradation of inhibitor of κB-α as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6’-bieckol. Conclusions These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-κB pathway in LPS-stimulated macrophages.</p

Sargaquinoic Acid Inhibits TNF-α-Induced NF-κB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs)

Sargaquinoic acid (SQA) has been known for its antioxidant and anti-inflammatory properties. This study investigated the effects of SQA isolated from Sargassum serratifolium on the inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). SQA decreased the expression of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 as well as chemotactic cytokines such as interleukin-8 and monocyte chemoattractant protein-1 in TNF-α-treated HUVECs. As a result, SQA prevented monocyte adhesion to TNF-α-induced adhesion. SQA also inhibited TNF-α-induced nuclear factor kappa B (NF-κB) translocation into the nucleus by preventing proteolytic degradation of inhibitor κB-α. Overall, SQA protects against TNF-α-induced vascular inflammation through inhibition of the NF-κB pathway in HUVECs. These data suggest that SQA may be used as a therapeutic agent for vascular inflammatory diseases such as atherosclerosis