Composite Membrane Based on Melamine Sponge and Boehmite Manufactured by Simple and Economical Dip-Coating Method for Fluoride Ion Removal.

The wastewater generated from the semiconductor production process contains a wide range and a large number of harmful substances at high concentrations. Excessive exposure to fluoride can lead to life-threatening effects such as skin necrosis and respiratory damage. Accordingly, a guideline value of fluoride ions in drinking water was 1.5 mg L-1 recommended by the World Health Organization (WHO). Polyvinylidene fluoride (PVDF) has the characteristics of excellent chemical and thermal stability. Boehmite (AlOOH) is a mineral and has been widely used as an adsorbent due to its high surface area and strong adsorption capacity for fluoride ions. It can be densely coated on negatively charged surfaces through electrostatic interaction due to its positively charged surface. In this study, a composite membrane was fabricated by a simple and economical dip coating of a commercial melamine sponge (MS) with PVDF and boehmite to remove fluoride ions from semiconductor wastewater. The prepared MS-PVDF-Boehmite composite membrane showed a high removal efficiency for fluoride ions in both incubation and filtration. By the incubation process, the removal efficiency of fluoride ions was 55% within 10 min and reached 80% after 24 h. In the case of filtration, the removal efficiency was 95.5% by 4 cycles of filtering with a flow rate of 70 mL h-1. In addition, the removal mechanism of fluoride ions on MS-PVDF-Boehmite was also explored by using Langmuir and Freundlich isotherms and kinetic analysis. (R2-1) From the physical, chemical, thermal, morphological, and mechanical analyses of present materials, this study provides an MS-PVDF-Boehmite composite filter material that is suitable for fluoride removal applications due to its simple fabrication process, cost-effectiveness, and high performance.

Early Enriched Environment Prevents Epigenetic p11 Gene Changes Induced by Adulthood Stress in Mice.

Positive experiences in early life may improve the capacity to cope with adulthood stress through epigenetic modification. We investigated whether an enriched environment (EE) in the postnatal period affected epigenetic changes in the p11 gene induced by chronic unpredictable stress (CUS) in adult C57BL/6J mice. EE was introduced for 5 weeks during postnatal days 21-55. After EE, the mice were subjected to CUS for 4 weeks. EE prevented depression-like behavior induced by adult CUS. EE prevented a decrease in p11 mRNA and histone H3 acetylation induced by CUS, with changes in the expression of histone deacetylase 5. Moreover, EE prevented changes in trimethylation of histone H3 lysine 4 (H3K4) and H3K27 induced by CUS. Furthermore, EE had positive effects on behavior and epigenetic alterations in adult mice without CUS. These results suggest that one of the underlying mechanisms of early-life EE may involve epigenetic modification of the hippocampal p11 gene promoter.

AMPA receptor-mTORC1 signaling activation is required for neuroplastic effects of LY341495 in rat hippocampal neurons.

The group II metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist LY341495 produces antidepressant-like effects by acting on mammalian target of rapamycin complex 1 (mTORC1) signaling and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in rodent. We investigated whether LY341495 affects neuroplasticity via these mechanisms in rat primary hippocampal cultures under conditions of dexamethasone (DEX)-induced neurotoxicity. Ketamine was used for comparison. Hippocampal cultures were treated with LY341495 under conditions of DEX-induced toxicity. Changes in mTORC1-mediated proteins were determined by Western blotting analyses. Changes in dendritic outgrowth and spine density were evaluated via immunostaining. LY341495 significantly prevented DEX-induced decreases in the levels of mTORC1, 4E-BP1, and p70S6K phosphorylation as well as the levels of the synaptic proteins. These effects were blocked by pretreatment with the AMPA receptor inhibitor 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo(f)quinoxaline (NBQX) and the mTORC1 inhibitor rapamycin. LY341495 significantly attenuated DEX-induced decreases in dendritic outgrowth and spine density. Pretreatment with rapamycin and NBQX blocked these effects of LY341495. Further analyses indicted that induction of BDNF expression produced by LY341495 was blocked by pretreatment with NBQX and rapamycin. LY341495 has neuroplastic effects by acting on AMPA receptor-mTORC1 signaling under neurotoxic conditions. Therefore, activation of AMPA receptor and mTORC1 signaling, which enhance neuroplasticity, may be novel targets for new antidepressants.

Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions.

The aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexamethasone-induced toxic conditions. Western blot analyses were performed to assess changes in mTORC1-mediated proteins, brain-derived neurotrophic factor (BDNF), and various synaptic proteins (PSD-95, synapsin I, and GluA1) in rat hippocampal cultures under toxic conditions induced by dexamethasone, which causes hippocampal cell death. Hippocampal dendritic outgrowth and spine formation were measured using immunostaining procedures. Dexamethasone significantly decreased the phosphorylation levels of mTORC1 as well as its downstream proteins. However, treatment with liraglutide prevented these reductions and significantly increased BDNF expression. The increase in BDNF expression was completely blocked by rapamycin and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Liraglutide also recovered dexamethasone-induced decreases in the total length of hippocampal dendrites and reductions in spine density in a concentration-dependent manner. However, the positive effects of liraglutide on neural plasticity were abolished by the blockade of mTORC1 signaling and AMPA receptors. Furthermore, liraglutide significantly increased the expression levels of PSD-95, synapsin I, and GluA1, whereas rapamycin and NBQX blocked these effects. The present study demonstrated that liraglutide activated mTORC1 signaling and AMPA receptor activity as well as increased dendritic outgrowth, spine density, and synaptic proteins under toxic conditions in rat primary hippocampal neurons. These findings suggest that GLP-1 receptor (GLP-1R) activation by liraglutide may affect neuroplasticity through mTORC1 and AMPA receptors.

Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats.

Recent studies have shown that antipsychotic drugs have epigenetic effects. However, the effects of antipsychotic drugs on histone modification remain unclear. Therefore, we investigated the effects of antipsychotic drugs on the epigenetic modification of the BDNF gene in the rat hippocampus. Rats were subjected to chronic restraint stress (6 h/d for 21 d) and then were administered with either olanzapine (2 mg/kg) or haloperidol (1 mg/kg). The levels of histone H3 acetylation and MeCP2 binding at BDNF promoter IV were assessed with chromatin immunoprecipitation assays. The mRNA levels of total BDNF with exon IV, HDAC5, DNMT1, and DNMT3a were assessed with a quantitative RT-PCR procedure. Chronic restraint stress resulted in the downregulation of total and exon IV BDNF mRNA levels and a decrease in histone H3 acetylation and an increase in MeCP2 binding at BDNF promoter IV. Furthermore, there were robust increases in the expression of HDAC5 and DNMTs. Olanzapine administration largely prevented these changes. The administration of haloperidol had no effect. These findings suggest that the antipsychotic drug olanzapine induced histone modification of BDNF gene expression in the hippocampus and that these epigenetic alterations may represent one of the mechanisms underlying the actions of antipsychotic drugs.

Epigenetic modification of glucocorticoid receptor promoter I7 in maternally separated and restraint-stressed rats.

Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes induced by environmental influences. Early life stress (ELS) has a persistent impact on GR expression, as well as behavior, in adult rodents via epigenetic changes of GR promoter I7. Moreover, various stressors can induce histone modifications in this region during adulthood. Thus, the present study aimed to investigate whether maternally separated (MS) rats exposed to chronic restraint stress (RS) would exhibit histone modifications of GR promoter I7 in the hippocampus. Rats were subjected to MS (3h per day) on postnatal days (PND) 1-21. Then, during adulthood (PND 56-77), the rats were exposed to RS (2h per day) followed by treatment with escitalopram (10mg/kg). The MS and RS groups exhibited significant decreases in total and exon I7 GR mRNA levels and the combination of MS and RS exerted a greater effect on these mRNA levels than either MS or RS alone. Additionally, both the MS and RS groups showed significant reductions in histone H3 acetylation at GR promoter I7 and the combination of MS and RS had a greater effect than did either MS or RS alone. Chronic escitalopram treatment ameliorated these changes. The present results indicate that postnatal MS and adult RS influence GR expression through histone modification at GR promoter I7, and that the combination of the two stressors potentiates these changes. Furthermore, epigenetic mechanisms are involved in escitalopram action.

AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells.

The intestinal epithelium plays a central role in immune homeostasis in the intestine. AhR, a ligand-activated transcription factor, plays an important role in diverse physiological processes. The intestines are exposed to various exogenous and endogenous AhR ligands. Thus, AhR may regulate the intestinal homeostasis, directly acting on the development of intestinal epithelial cells (IEC). In this study, we demonstrated that 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited the in vitro development of mouse intestinal organoids. The number of Paneth cells in the small intestine and the depth of crypts of the small and large intestines were reduced in mice administrated with FICZ. Immunohistochemical and flow cytometric assays revealed that AhR was highly expressed in Lgr5(+) stem cells. FICZ inhibited Wnt signaling lowering the level of ß-catenin protein. Gene expression analyses demonstrated that FICZ increased expression of Lgr5, Math1, BMP4, and Indian Hedgehog while inhibiting that of Lgr4.

Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1.

Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and are preferentially expressed in innate immune cells. TLR-mediated activation of these cells activates the adaptive immune system. However, it has become clear that TLRs are not only expressed but also functionally active in CD4 T cells. The intestines are continuously exposed to TLR ligands, including lipopolysaccharide (LPS), a TLR4 ligand, and TLR4 is expressed higher in Th17 cells than Th1 and Th2 cells. In addition, development of Th17 cells in the gut mucosa is more dependent on gut microbiota than Th1, Th2, and Treg. Thus, we examined whether LPS directly regulates Th17 differentiation. LPS directly stimulated Th17 differentiation in vitro. In Th17 cells, LPS increased phosphorylation of NF-κB1, resulting in an increase of p50, the processed form of NF-κB1, whereas it decreased phosphorylation of RelB, leading to the up-regulation of RelB. Subcutaneous injection of LPS increased the frequency of IL-17 producing cells in inguinal lymph nodes, worsening experimental autoimmune encephalomyelitis (EAE). Additionally, expression of TLR1, TLR2, TLR4, and TLR5 was reduced upon T cell activation and LPS showed modest effect on TLR4 expression. These findings provide the first evidence that TLR4 activation directly regulate Th17 differentiation.

3,3'-Diindolylmethane Inhibits Flt3L/GM-CSF-induced-bone Marrow-derived CD103(+) Dendritic Cell Differentiation Regulating Phosphorylation of STAT3 and STAT5.

The intestinal immune system maintains oral tolerance to harmless antigens or nutrients. One mechanism of oral tolerance is mediated by regulatory T cell (Treg)s, of which differentiation is regulated by a subset of dendritic cell (DC)s, primarily CD103(+) DCs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating immunity. The intestines are exposed to various AhR ligands, including endogenous metabolites and phytochemicals. It was previously reported that AhR activation induced tolerogenic DCs in mice or in cultures of bone marrow-derived DCs. However, given the variety of tolerogenic DCs, which type of tolerogenic DCs is regulated by AhR remains unknown. In this study, we found that AhR ligand 3,3'-diindolylmethane (DIM) inhibited the development of CD103(+) DCs from mouse bone marrow cells stimulated with Flt3L and GM-CSF. DIM interfered with phosphorylation of STAT3 and STAT5 inhibiting the expression of genes, including Id2, E2-2, IDO-1, and Aldh1a2, which are associated with DC differentiation and functions. Finally, DIM suppressed the ability of CD103(+) DCs to induce Foxp3(+) Tregs.