Psychological mistreatment by married children in Korea: using the contextual theory to explain mistreatment of aging parents and parents-in-law.

Guided by the contextual theory of elder mistreatment, this study examined the psychological mistreatment (PM) of aging parents and parents-in-law by their married children and compared the risk factors of PM. We used nationally representative data on the adverse experiences of Korean adults in 2017 (n=2,974). Results showed similarities and differences in the PM of aging parents and parents-in-law. Common risk factors included children's sex, greater victimization experiences, and co-residence. Daughters and daughters-in-law were more likely than their male counterparts to psychologically mistreat parents and parents-in-law. While parents' PM was more frequent when children had a temporary work status and when parents were younger, PM of parents-in-law occurred more often when children had a full-time job, poor self-rated health, and a negative perception of family relations. These findings provide insights into policy intervention against PM, suggesting the need for complex prevention strategies for PM of aging parents and parents-in-law.

Discovery and optimization of ATX inhibitors via modeling, synthesis and biological evaluation.

Autotaxin (ATX) is a potential target for the treatment of various cancers. A new series of ATX inhibitors was rationally designed and synthesized based on our previous study. Biological evaluation and structure-activity relationship (SAR) of this series are discussed. Among fourteen synthesized derivatives, six compounds (2, 3, 4, 12, 13 and 14) exhibited enhanced ATX inhibitory activities with IC50 values in the low nanomolar range. Molecular interactions of all the synthesized compounds within the active site of ATX were studied through molecular docking studies. Herein, we describe our lead optimization efforts that resulted in the identification of a potent ATX inhibitor (compound 4 with IC50 = 1.23 nM, FS-3 and 2.18 nM, bis-pNPP). Furthermore, pharmacokinetic properties of this most promising compound are profiled.

Design, synthesis, docking and biological evaluation of 4-phenyl-thiazole derivatives as autotaxin (ATX) inhibitors.

The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is involved in several human diseases such as cancer, autoimmune diseases, inflammatory diseases neurodegenerative diseases and fibrotic diseases. Herein, a series of 4-phenyl-thiazole based compounds was designed and synthesized. Compounds were evaluated for their ATX inhibitory activity using FS-3 and human plasma assays. In the FS-3 assay, compounds 20 and 21 significantly inhibited the ATX at low nanomolar level (IC50=2.99 and 2.19nM, respectively). Inhibitory activity of 21 was found to be slightly better than PF-8380 (IC50=2.80nM), which is one of the most potent ATX inhibitors reported till date. Furthermore, 21 displayed higher potency (IC50=14.99nM) than the first clinical ATX inhibitor, GLPG1690 (IC50=242.00nM) in the human plasma assay. Molecular docking studies were carried out to explore the binding pattern of newly synthesized compounds within active site of ATX. Docking studies suggested the putative binding mode of the novel compounds. Good ATX inhibitory activity of 21 was attributed to the hydrogen bonding interactions with Asn230, Trp275 and active site water molecules; electrostatic interaction with catalytic zinc ion and hydrophobic interactions with amino acids of the hydrophobic pocket.

Household food insecurity during childhood and subsequent health status: the early childhood longitudinal study--kindergarten cohort.

OBJECTIVES: We examined long-term patterns of household food insecurity in children from kindergarten through eighth grade and the association between those patterns and children's proxy-reported health status in eighth grade. METHODS: We obtained data from the Early Childhood Longitudinal Study-Kindergarten Cohort, a study that followed a nationally representative sample of students from kindergarten entry in 1998-1999 through eighth grade. We classified food insecurity according to the number of years of reported household food insecurity over 4 observation years. We estimated logistic regression models to estimate the association between cumulative food insecurity exposure and health outcomes. RESULTS: Food insecurity was generally a transient rather than a persistent condition. Persistent food insecurity over the 9-year period was associated with lower health status in eighth grade, whereas more transient food insecurity was not significantly associated with health outcomes in most models. CONCLUSIONS: Single-year estimates substantially underestimate the share of children whose households experienced food insecurity at some point during their childhood years. Persistent food insecurity is an important public health issue for children. Policy interventions to alleviate children's persistent food insecurity may promote child health.

Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells.

Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.