PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury

FK506 binding protein 12 (FK506BP) is a small peptide with a single FK506BP domain that is involved in suppression of immune response and reactive oxygen species. FK506BP has emerged as a potential drug target for several inflammatory diseases. Here, we examined the protective effects of directly applied cell permeable FK506BP (PEP-1-FK506BP) on corneal alkali burn injury (CAI). In the cornea, there was a significant decrease in the number of cells expressing pro-inflammation, apoptotic, and angiogenic factors such as TNF-α, COX-2, and VEGF. Both corneal opacity and corneal neovascularization (CNV) were significantly decreased in the PEP-1-FK506BP treated group. Our results showed that PEP-1-FK506BP can significantly inhibit alkali burn-induced corneal inflammation in rats, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors and inflammatory cytokines. These results suggest that PEP-1-FK506BP may be a potential therapeutic agent for CAI. [BMB Reports 2015; 48(11): 618-623]     

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of blood vessels in the hippocampus 6 h after LPS treatment, judging from double immunofluorescence study with platelet-derived endothelial cell adhesion molecule-1 (PECAM-1, a marker for endothelial cells): it decreased 12 h and disappeared 24 h after LPS treatment. In addition, the ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive (⁺) microglia were morphologically activated in the mouse hippocampus after LPS treatment. At 24 h after LPS treatment, Iba-1⁺ microglia of activated forms were abundant in the hippocampus. However, NeuN (a neuron-specific soluble nuclear antigen)⁺ neurons were not significantly changed in the hippocampus after LPS treatment. Fluoro-jade B (a marker for neuronal degeneration)⁺ cells were not detected in the hippocampus at any time after LPS treatment. In addition, there were no significant differences in permeability of blood–brain barriers at any time points after LPS treatment. In brief, our results indicate that intraperitoneal administration of 1 mg/kg LPS effectively induces LPS receptor (TLR4) expression in the hippocampus, and the treatment increases corticosterone levels, inflammation in the blood vessels, and microglial activation in the hippocampus without any neuronal damage.     

Examining Impacts of Allergic Diseases on Psychological Problems and Tobacco Use in Korean Adolescents: The 2008–2011 Korean National Health and Nutrition Examination Survey

Purpose

Asthma during adolescence can induce social, psychological, and behavioral problems. We examined the impact of asthma and other allergic diseases on psychological symptoms and health risk behaviors among South Korean adolescents.

Methods

In this population-based cross-sectional study, 3192 adolescents (10–18 years of age) participating in the 2008–2011 Korean National Health and Nutrition Examination Survey were enrolled. Psychological problems associated with clinically diagnosed asthma, allergic rhinitis, and atopic dermatitis were assessed using questionnaires and surveys. Data was analyzed using logistic regression to determine the association of depression with allergic disease while controlling for age, sex, body mass index, smoking experience, and alcohol use.

Results

Asthma and atopic dermatitis were associated with a higher prevalence of depression (17.2% and 13%, respectively). After adjusting for the covariates, asthma patients were approximately two times as likely to have depression as non-allergic participants (odds ratio, 1.81; 95% confidence interval, 1.22–2.68). Psychosocial stress significantly increased in the following order: no allergy, any allergy without asthma, asthma only, and asthma with any allergy (p for linear trend = 0.01). The asthma without other allergies group showed the highest prevalence of cigarette smoking (p = 0.007).

Conclusions

In this study, asthma with or without other allergies was significantly related to increases in depression, psychosocial stress, and smoking experience. Thus, care should be taken to adjust treatment to account for the psychological symptoms and health risk behaviors common among asthmatic adolescents.     

Associations between interleukin-23 receptor polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether interleukin-23 receptor (IL-23R) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-23R rs1343151, rs10489629, rs7517847, rs11209026, rs1004819, and rs2201841 polymorphisms and RA using (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 13 studies from eight articles involving 10,016 RA patients and 11,967 controls were considered in the meta-analysis. Meta-analysis identified a significant association between RA and the A allele of the rs1343151 polymorphism in the overall population (OR?=?1.110, 95?% CI?=?1.056–1.168, p?=?4.7?×?10^?6). Stratification by ethnicity identified a significant association between this polymorphism and RA in Europeans (OR?=?1.105, 95?% CI?=?1.049–1.163, p?=?1.4?×?10^?5). An association was also found between RA and the A allele carrier of the rs1343151 polymorphism in Europeans (OR?=?1.135, 95?% CI?=?1.058–1.217, p?=?4.0?×?10^?5). Meta-analysis revealed a significant association between RA and the A allele of the rs10489629 polymorphism in the overall population (OR?=?1.079, 95?% CI?=?1.029–1.131, p?=?0.002) and in Europeans (OR?=?1.092, 95?% CI?=?1.038–1.149, p?=?0.001). Meta-analyses of recessive, dominant, and additive models showed the same pattern as the meta-analysis of the A allele of the rs10489629 polymorphism, that is, a significant association with RA in Europeans. However, no association was found between the IL-23R rs7517847, rs11209026, rs1004819, and rs2201841 polymorphisms and RA susceptibility. This meta-analysis shows that the IL-23R rs1343151 and rs10489629 polymorphisms are associated with the development of RA in Europeans. These findings suggest that the IL-23R genes confer susceptibility to RA in the European population, but further study of this association is required in other ethnic groups.     

Coexposure to environmental tobacco smoke increases levels of allergen-induced airway remodeling in mice

Environmental tobacco smoke (ETS) can increase asthma symptoms and the frequency of asthma attacks. However, the contribution of ETS to airway remodeling in asthma is at present unknown. In this study, we have used a mouse model of allergen-induced airway remodeling to determine whether the combination of chronic exposure to ETS and chronic exposure to OVA allergen induces greater levels of airway remodeling than exposure to either chronic ETS or chronic OVA allergen alone. Mice exposed to chronic ETS alone did not develop significant eosinophilic airway inflammation, airway remodeling, or increased airway hyperreactivity to methacholine. In contrast, mice exposed to chronic OVA allergen had significantly increased levels of peribronchial fibrosis, increased thickening of the smooth muscle layer, increased mucus, and increased airway hyperreactivity which was significantly enhanced by coexposure to the combination of chronic ETS and chronic OVA allergen. Mice coexposed to chronic ETS and chronic OVA allergen had significantly increased levels of eotaxin-1 expression in airway epithelium which was associated with increased numbers of peribronchial eosinophils, as well as increased numbers of peribronchial cells expressing TGF-beta1. These studies suggest that chronic coexposure to ETS significantly increases levels of allergen-induced airway remodeling (in particular smooth muscle thickness) and airway responsiveness by up-regulating expression of chemokines such as eotaxin-1 in airway epithelium with resultant recruitment of cells expressing TGF-beta1 to the airway and enhanced airway remodeling.     

Synthesis, in vitro assay, and molecular modeling of new piperidine derivatives having dual inhibitory potency against acetylcholinesterase and Abeta1-42 aggregation for Alzheimer's disease therapeutics

With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized new piperidine derivatives having dual action of acetylcholinesterase (AChE) and beta-amyloid peptide (Abeta) aggregation inhibition. For binding with the catalytic site of AChE, an ester with aromatic group was designed, and for the peripheral site, another aromatic group was considered. And for intercalating amyloid-beta oligomerization, long and linear conformation with a lipophilic group was considered. The synthetic methods employed for the structure with dual action depended on alcohols with an aromatic ring and the substituted benzoic acids, which are esterificated in the last step of the synthetic pathway. We screened these new derivatives through inhibition tests of acetylcholinesterase, butyrylcholinesterase (BChE), and Abeta(1-42) peptide aggregation, AChE-induced Abeta(1-42) aggregation. Our results displayed that compound 12 showed the best inhibitory potency and selectivity of AChE, and 29 showed the highest selectivity of BChE inhibition. Compounds 15 and 12 had inhibitory activities against Abeta(1-42) aggregation and AChE-induced Abeta aggregation. In the docking model, we confirmed that 4-chlorobenzene of 12 plays the parallel pi-pi stacking against the indole ring of Trp84 in the bottom gorge of AChE. Because the benzyhydryl moiety of 12 covered the peripheral site of AChE in a funnel-like shape, 12 showed good inhibitory potency against AChE and could inhibit AChE-induced Abeta(1-42) peptide aggregation.     

Biodegradable molecularly imprinted polymers based on poly(ε-caprolactone)

Novel biodegradable molecularly imprinted polymers (MIPs) based on poly(ε-caprolactone) (PCL) were prepared by combining two important properties required of ideal biomaterials, biodegradability (with biocompatibility) and molecular recognition properties. Acrylate or methacrylate end-capped PCL macromers were synthesized through the reaction of PCL diol or triol with acryloyl or methacryloyl chloride. The synthesis of acrylate or methacrylate end-capped macromers was confirmed using FT-IR and H NMR spectroscopic techniques. These macromers were used to prepare biodegradable crosslinked networks by photopolymerization with functional monomer (acrylic acid) and a model template (theophylline). The theophylline-imprinted polymer showed higher binding capacity for theophylline compared with non-imprinted polymer (NIP), and also showed selectivity for theophylline over caffeine (similar structure molecules). PCL-based MIP degraded 8% of the initial weight in 30 days in phosphate-buffered saline (PBS) solution (pH 7.4) and over 90% of the initial weight within 24 h in 1 N NaOH at 37°C.     

Current theories for mechanism of stomatal opening: Influence of blue light; mesophyll cells,and sucrose

Since the late 1960s, researchers have observed that starch in the chloroplasts of the guard cells breaks down during the day and accumulates in the dark. Based on this, carbohydrates have historically been regarded as the primary osmotica modulating stomatal opening. However, the discovery of an important role for potassium uptake has led to the replacement of that starch-sugar hypothesis. Current research now focuses mainly on how K⁺ is transported in and out of cells when the stomata open or close. However, questions remain concerning photoreceptors, and the functioning of guard cell chloroplasts is still disputed. Coincidentally, some recent study results have again suggested that sucrose may play a major role in guard cell osmoregulation, thus supporting the original theory of starch-sugar involvement.