ORIGINAL ARTICLE: Associations of antidepressant medication with its various predictors including particulate matter: Machine learning analysis using national health insurance data.

This study uses machine learning and population-based data to analyze major determinants of antidepressant medication including the concentration of particulate matter under 2.5 µm (PM2.5). Retrospective cohort data came from Korea National Health Insurance Service claims data for 43,251 participants, who were aged 15-79 years, lived in the same districts of Seoul and had no history of antidepressant medication during 2002-2012. The dependent variable was antidepressant-free months during 2013-2015 and the 30 independent variables for 2012 were included (demographic/socioeconomic information, health information, district-level information including PM2.5). Random forest variable importance, the contribution of a variable for the performance of the model, was used for identifying major predictors of antidepressant-free months. Based on random forest variable importance, the top 15 determinants of antidepressant medication during 2013-2015 included cardiovascular disease (0.0054), age (0.0047), household income (0.0037), gender (0.0027), the district-level proportion of recipients of national basic living security program benefits (0.0019), district-level social satisfaction (0.0013), diabetes mellitus (0.0012), January 2012 PM2.5 (0.0011), district-level street ratio (0.0010), drinker (0.0009), chronic obstructive pulmonary disease (0.0008), district-level economic satisfaction (0.0006), exercise (0.0005), March 2012 PM2.5 (0.0005) and November 2012 PM2.5 (0.0004). Besides these predictors, smoker and district-level deprivation index are found to be influential most widely, given that they ranked within the top 10 most often in sub-group analysis. In conclusion, antidepressant medication has strong associations with neighborhood conditions including socioeconomic satisfaction and the seasonality of particulate matter. Strong interventions for these factors are really needed for the effective management of major depressive disorder.

Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma.

S100A8 and S100A9 are important proteins in the pathogenesis of allergy. Asthma is an allergic lung disease, characterized by bronchial inflammation due to leukocytes, bronchoconstriction, and allergen-specific IgE. In this study, we examined the role of S100A8 and S100A9 in the interaction of cytokine release from bronchial epithelial cells, with constitutive apoptosis of neutrophils. S100A8 and S100A9 induce increased secretion of neutrophil survival cytokines such as MCP-1, IL-6 and IL-8. This secretion is suppressed by TLR4 inhibitor), LY294002, AKT inhibitor, PD98059, SB202190, SP600125, and BAY-11-7085. S100A8 and S100A9 also induce the phosphorylation of AKT, ERK, p38 MAPK and JNK, and activation of NF-κB, which were blocked after exposure to TLR4i, LY294002, AKTi, PD98059, SB202190 or SP600125. Furthermore, supernatants collected from bronchial epithelial cells after S100A8 and S100A9 stimulation suppressed the apoptosis of normal and asthmatic neutrophils. These inhibitory mechanisms are involved in suppression of caspase 9 and caspase 3 activation, and BAX expression. The degradation of MCL-1 and BCL-2 was also blocked by S100A8 and S100A9 stimulation. Essentially, neutrophil apoptosis was blocked by co-culture of normal and asthmatic neutrophils with BEAS-2B cells in the presence of S100A8 and S100A9. These findings will enable elucidation of asthma pathogenesis.

Chaenomeles sinensis Koehne extract suppresses the development of atopic dermatitis-like lesions by regulating cytokine and filaggrin expression in NC/Nga mice.

Chaenomeles sinensis Koehne (CS) has been used in a traditional oriental medicine for treating throat diseases, anaphylaxis, viral infection, and inflammation. This study investigated the underlying mechanism of anti-allergic effect of CS. Leaves of CS plants were dried, powdered, and then underwent extraction with DMSO. Both ELISA and western blotting were performed to evaluate cytokine concentration and the expression and activation of filaggrin and JNK. Five-week-old female NC/Nga mice were used as an AD-like mouse model by treating them with 2,4-dinitrochlorobenzene (DNCB). The secretion of TARC, MCP-1, and IL-8 is increased by TNF-α and IFN-γ in HaCaT cells, and CS extract inhibited the increased production of TARC, MCP-1, and IL-8. TNF-α and IFN-γ suppressed filaggrin expression by activating JNK. CS extract recovered the expression of filaggrin decreased by TNF-α and IFN-γ by blocking the activation of JNK. In vivo experiment, CS administration reduced thickening of the epidermis and infiltration of inflammatory cells into the dermis as compared to DNCB treatment. Moreover, the decrease of filaggrin expression due to DNCB treatment was recovered by CS administration. The serum IgE level was decreased by CS treatment. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A, and the secretions of IL-4, IL-5, IL-13 and eotaxin were lower in the CS-treated group than in the DNCB group. These results may contribute to the development of a CS-based drug for the treatment of atopic dermatitis.

Poncirus Trifoliata (L.) Raf. Extract Inhibits the Development of Atopic Dermatitis-like Lesions in Human Keratinocytes and NC/Nga mice.

This study investigated the anti-allergic effect of Poncirus trifoliata (L.) Raf. (PT) on human keratinocytic HaCaT cells in vitro and on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like lesions in vivo. The release of TARC, MCP-1, IL-6 and IL-8 is increased by IFN-γ and TNF-α in HaCaT cells, and PT extract suppressed the increased production of TARC, MCP-1, IL-6, and IL-8. PT extract recovered the expression of filaggrin decreased by IFN-γ and TNF-α. in vivo experiment, PT administration decreased the skin severity score, thickening of the epidermis, movement of inflammatory cells into the dermis, and serum IgE level as compared to DNCB treatment. Moreover, the decrease of filaggrin and loricrin induced by DNCB treatment was recovered by PT administration. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A, and the secretions of IL-4, IL-5, IL-13 and eotaxin were lower in the PT-treated group than in the DNCB group. These findings may indicate that PT is useful in drug development for the treatment of AD.