Intracellular sphingosine kinase 2-derived sphingosine-1-phosphate mediates epidermal growth factor-induced ezrin-radixin-moesin phosphorylation and cancer cell invasion.

The bioactive sphingolipid sphingosine-1-phosphate (S1P) mediates cellular proliferation, mitogenesis, inflammation, and angiogenesis. These biologies are mediated through S1P binding to specific GPCRs [sphingosine-1-phosphate receptor (S1PR)1-5] and some other less well-characterized intracellular targets. Ezrin-radixin-moesin (ERM) proteins, a family of adaptor molecules linking the cortical actin cytoskeleton to the plasma membrane, are emerging as critical regulators of cancer invasion via regulation of cell morphology and motility. Recently, we identified S1P as an acute ERM activator (via phosphorylation) through its action on S1PR2. In this work, we dissect the mechanism of S1P generation downstream of epidermal growth factor (EGF) leading to ERM phosphorylation and cancer invasion. Using pharmacologic inhibitors, small interfering RNA technologies, and genetic approaches, we demonstrate that sphingosine kinase (SK)2, and not SK1, is essential and sufficient in EGF-mediated ERM phosphorylation in HeLa cells. In fact, knocking down SK2 decreased ERM activation 2.5-fold. Furthermore, we provide evidence that SK2 is necessary to mediate EGF-induced invasion. In addition, overexpressing SK2 causes a 2-fold increase in HeLa cell invasion. Surprisingly, and for the first time, we find that this event, although dependent on S1PR2 activation, does not generate and does not require extracellular S1P secretion, therefore introducing a potential novel model of autocrine/intracrine action of S1P that still involves its GPCRs. These results define new mechanistic insights for EGF-mediated invasion and novel actions of SK2, therefore setting the stage for novel targets in the treatment of growth factor-driven malignancies.

Effects of Green Network Management of Urban Street Trees on Airborne Particulate Matter (PM2.5) Concentration.

Street trees are crucial for air pollutant reduction in urban areas. Herein, we used computational fluid dynamics (CFD) simulation to identify changes in airborne particulate matter (PM2.5) concentration based on wind characteristics (direction and velocity) and the green network of street trees. The green network was assessed based on composition of the green area of street trees in the central reserve area and between the motor and pedestrian roads. The PM2.5 concentration varied according to the presence or absence of major reserve planting and the planting structure of the street trees, but not according to the wind direction or velocity. The concentration was lower when the wind direction was 45° (than when the wind direction was 0°), whereas it showed a more significant decrease as the wind velocity increased. Despite variation at each measurement site, the PM2.5 reduction was generally higher when the central reserve and street trees had a multi-planting structure. Hence, to ensure an effective reduction in the PM2.5 concentration on motor roads and reduce its negative impact on pedestrians, both arbors and shrubs should be planted in the central reserve area. The study results will serve as reference for managing the green area network and linear green infrastructure in terms of improving the atmospheric environment.

Lactobacillus paracasei ATG-E1 improves particulate matter 10 plus diesel exhaust particles (PM10D)-induced airway inflammation by regulating immune responses.

Particulate matter (PM) exposure can adversely affect respiratory function. Probiotics can alleviate the inflammatory responses in respiratory diseases. We examined the protective effects of Lactobacillus paracasei ATG-E1 isolated from the feces of a newborn baby against airway inflammation in a PM10 plus diesel exhaust particle (DEP) (PM10D)-induced airway inflammation model. BALB/c mice were exposed to PM10D by intranasal injection three times at 3-day intervals for 12 days, and L. paracasei ATG-E1 was administered orally for 12 days. Analysis of immune cell population and expression of various inflammatory mediators and gut barrier-related genes were determined in bronchoalveolar lavage fluid (BALF), lung, peyer's patch, and small intestine. A histological analysis of the lungs was performed. In addition, the in vitro safety and their safety in genomic analyses were examined. L. paracasei ATG-E1 was found to be safe in vitro and by genomic analysis. L. paracasei ATG-E1 suppressed neutrophil infiltration and the number of CD4+, CD4+CD69+, CD62L-CD44+high, CD21/35+B220+, and Gr-1+CD11b+ cells, as well as the expression of inflammatory mediators, including chemokine (C-X-C motif) ligand (CXCL)-1, macrophage inflammatory protein (MIP)-2, interleukin (IL)-17a, tumor necrosis factor (TNF)-α, and IL-6 in BALF and lungs in PM10D-induced airway inflammation. It protected against histopathological damage in the lungs of mice with PM10D-induced airway inflammation. L. paracasei ATG-E1 concomitantly increased the expression levels of the gut barrier function-related genes occludin, claudin-1, and IL-10 in the small intestine, with an increased number of CD4+ and CD4+CD25+ immune cells in the peyer's patch. L. paracasei ATG-E1 suppressed immune activation and airway inflammatory responses in the airways and lungs by restoring the lung damage by PM10D. It also regulated intestinal immunity and ameliorated the gut barrier function in the ileum. These results indicate the potential of L. paracasei ATG-E1 as an protective and therapeutic agent against airway inflammation and respiratory diseases.

Morphological, Ecological, and Molecular Divergence of Conogethes pinicolalis from C. punctiferalis (Lepidoptera: Crambidae).

Conogethes pinicolalis has long been considered as a Pinaceae-feeding type of the yellow peach moth, C. punctiferalis, in Korea. In this study, the divergence of C. pinicolalis from the fruit-feeding moth C. punctiferalis was analyzed in terms of morphology, ecology, and genetics. C. pinicolalis differs from C. punctiferalis in several morphological features. Through field observation, we confirmed that pine trees are the host plants for the first generation of C. pinicolalis larvae, in contrast to fruit-feeding C. punctiferalis larvae. We successfully reared C. pinicolalis larvae to adults by providing them pine needles as a diet. From a genetic perspective, the sequences of mitochondrial COI of these two species substantially diverged by an average of 5.46%; moreover, phylogenetic analysis clearly assigned each species to an independent clade. On the other hand, nuclear EF1α showed a lower sequence divergence (2.10%) than COI. Overall, EF1α-based phylogenetic analysis confirmed each species as an independent clade, but a few haplotypes of EF1α indicated incomplete lineage sorting between these two species. In conclusion, our results demonstrate that C. pinicolalis is an independent species according to general taxonomic criteria; however, analysis of the EF1α sequence revealed a short divergence time.

Morphological and Chemical Evaluations of Leaf Surface on Particulate Matter2.5 (PM2.5) Removal in a Botanical Plant-Based Biofilter System.

Particulate matter has been increasing worldwide causing air pollution and serious health hazards. Owing to increased time spent indoors and lifestyle changes, assessing indoor air quality has become crucial. This study investigated the effect of watering and drought and illumination conditions (constant light, light/dark cycle, and constant dark) on particulate matter2.5 (PM2.5) removal and surface characterization of leaf in a botanical plant-based biofilter system. Using Ardisia japonica and Hedera helix as experimental plants in the plant-based biofilter system, PM2.5, volatile organic carbon, and CO2, as the evaluators of indoor air quality, were estimated using a sensor. Morphological and chemical changes of the leaf surface (i.e., roughness and wax) associated with PM2.5 removal were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and atomic force microscopy. The highest PM2.5 removal efficiency, stomata closure, high leaf roughness, and wax layer were observed under drought with constant light condition. Consequently, PM2.5 removal was attributed to the combined effect of leaf roughness and wax by adsorption rather than stomatal uptake. These results suggest that operating conditions of indoor plant-based biofilter system such as watering (or drought) and illumination may be applied as a potential strategy for enhancing PM2.5 removal.

Therapeutic Effect of Chung-Pae, an Experimental Herbal Formula, on Acute Lung Inflammation Is Associated with Suppression of NF- κ B and Activation of Nrf2.

Acute lung injury (ALI) is an inflammatory disease with high mortality, but therapeutics against it is unavailable. Recently, we elaborated a formula, named Chung-pae (CP), that comprises four ethnic herbs commonly prescribed against various respiratory diseases in Asian traditional medicine. CP is being administered in aerosol to relieve various respiratory symptoms of patients in our clinic. Here, we sought to examine whether CP has a therapeutic effect on ALI and to uncover the mechanism behind it. Reporter assays show that CP suppressed the transcriptional activity of proinflammatory NF- κ B and activated that of anti-inflammatory Nrf2. Similarly, CP suppressed the expression of NF- κ B dependent, proinflammatory cytokines and induced that of Nrf2 dependent genes in RAW 264.7. An aerosol intratracheal administration of CP effectively reduced neutrophilic infiltration and the expression of pro-inflammatory cytokines, hallmarks of ALI, in the lungs of mice that received a prior intraperitoneal injection of lipopolysaccharide. The intratracheal CP administration concomitantly enhanced the expression of Nrf2 dependent genes in the lung. Therefore, our results evidenced a therapeutic effect of CP on ALI, in which differential regulation of the two key inflammatory factors, NF- κ B and Nrf2, was involved. We propose that CP can be a new therapeutic formula against ALI.