The CD36 scavenger receptor Bez regulates lipid redistribution from fat body to ovaries in Drosophila.

Lipid distribution in an organism is mediated by the interplay between lipoprotein particles, lipoprotein receptors and class B scavenger receptors of the CD36 family. CD36 is a multifunctional protein mediating lipid uptake, mobilization and signaling at the plasma membrane and inside of the cell. The CD36 protein family has 14 members in Drosophila melanogaster, which allows for the differentiated analysis of their functions. Here, we unravel a role for the so far uncharacterized scavenger receptor Bez in lipid export from Drosophila adipocytes. Bez shares the lipid binding residue with CD36 and is expressed at the plasma membrane of the embryonic, larval and adult fat body. Bez loss of function lowers the organismal availability of storage lipids and blocks the maturation of egg chambers in ovaries. We demonstrate that Bez interacts with the APOB homolog Lipophorin at the plasma membrane of adipocytes and trace the Bez-dependent transfer of an alkyne-labeled fatty acid from adipocytes to Lipophorin. Our study demonstrates how lipids are distributed by scavenger receptor-lipoprotein interplay and contribute to the metabolic control of development.

Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation.

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1ß induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1ß induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.

Filling gaps between exposure modeling and the analysis of urinary biomarkers using personal air monitoring: An intervention study of permethrin used in home insecticide spray.

Permethrin is one of the most widely used active ingredients in spray-type home insecticides. However, indoor permethrin exposure resulting from the use of home insecticides is not well-characterized, as measured permethrin concentrations in indoor environmental and biological media with a known application rate are scarce. We conducted an intervention study with four participants for seven days. We conducted personal air monitoring and collected 24-h urine samples in which we quantified time-weighted average (TWA) permethrin concentrations in indoor air (Cair ) and urinary concentrations of two permethrin metabolites, 3-phenoxybenzoic acid (3-PBA) and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis/trans-DCCA). We also estimated (1) TWA Cair using a simple indoor air model and (2) urinary excreted (UE) mass using a simple excretion model with both estimated and measured TWA Cair . Measurements of TWA Cair from personal air monitoring were lower than those estimated from the indoor model by a factor of 2.9 to 49.4. The ratio of estimated to measured UE mass ranged 3.5-18.2 when using estimated TWA Cair and 1.1-2.9 when using measured TWA Cair . Smaller ratios in estimating internal permethrin exposure from personal air monitoring suggest that personal air monitoring could reduce uncertainties in permethrin exposure assessment resulting from the use of spray-type insecticides.

A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma.

We aimed to create an animal model for hepatocellular carcinoma (HCC) with a short time, a high survival rate, as well as a high incidence of HCC in both males and females than previously reported. The Diethylnitrosamine (DEN) model has an age-related effect. A single dose of DEN treatment is not enough in young mice up to 50 weeks. The same pattern is shown in an adult with multiple-dose trials whether or not there is some promotion agent. In this study, two-week old C57BL6 mice were given a total of eight doses of DEN, initially 20mg/kg body weight, and then 30mg/kg in the third week, followed by 50mg/kg for the last six weeks. The first group is DEN treatment only and the other two groups received thioacetamide (TAA) treatment for four or eight weeks after one week of rest from the last DEN treatment. An autopsy was performed after 24 weeks of the initial dose of DEN in each group. The cellular arrangement of HCC in the entire group was well-differentiated carcinoma and tumor presence with no significant impact on the survival of mice. Increased levels of the biochemical markers in serum, loss of tissue architecture, hepatocyte death, and proliferation were highly activated in all tumor-induced groups. This finding demonstrates an improved strategy to generate an animal model with a high occurrence of tumors combined with cirrhosis in a short time regardless of sex for researchers who want to investigate liver cancer-related.

Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272 and MG4577 Modulate Allergic Inflammatory Response in RAW 264.7 and RBL-2H3 cells.

Allergic inflammation refers to a hyperimmune reaction that causes hypersensitivity responses such as hives, itchiness, runny nose, and cough due to specific allergens. Allergic diseases are known to be influenced by the diversity and distribution of intestinal microbiota, and Lactobacill is known to relieve allergic symptoms by modulating cytokines secreted by T helper type 1 (Th1)/Th2 cells. This study was designed to investigate the effects of Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272, MG4577, and MG4657 on levels of pro-inflammatory cytokines and proteins associated with allergic symptoms in RAW 264.7 macrophages, and RBL-2H3 mast cells, as well as their probiotic properties. MG4247, MG4272, and MG4577 significantly reduced tumor necrosis factor-α and interleukin (IL)-6 levels in LPS-induced RAW 264.7 macrophages, and markedly decreased IL-4, IL-5, and IL-13 levels and STAT6 phosphorylation in DNP-IgE/HSA sensitized RBL-2H3 mast cells. Furthermore, MG4247, MG4272, and MG4577 tolerated the acidic condition with pepsin and basic condition with bile salt, and showed a high adhesion rate (≥ 73.9%). In safety evaluation, MG4247, MG4272, and MG4577 showed no hemolytic or bile salt hydrolase activity and no cytotoxicity to HT-29 cells (≥ 96.7%). Hence, MG4272, MG4272, and MG4577 can be used as candidate probiotic strains to relieve cytokines associated with allergic inflammation.

Spatial Uncertainty in Modeling Inhalation Exposure to Volatile Organic Compounds in Response to the Application of Consumer Spray Products.

(1) Background: Mathematical exposure modeling of volatile organic compounds (VOCs) in consumer spray products mostly assumes instantaneous mixing in a room. This well-mixed assumption may result in the uncertainty of exposure estimation in terms of spatial resolution. As the inhalation exposure to chemicals from consumer spray products may depend on the spatial heterogeneity, the degree of uncertainty of a well-mixed assumption should be evaluated under specific exposure scenarios. (2) Methods: A room for simulation was divided into eight compartments to simulate inhalation exposure to an ethanol trigger and a propellant product. Real-time measurements of the atmospheric concentration in a room-sized chamber by proton transfer reaction mass spectrometry were compared with mathematical modeling to evaluate the non-homogeneous distribution of chemicals after their application. (3) Results: The well-mixed model overestimated short-term exposure, particularly under the trigger spray scenario. The uncertainty regarding the different chemical proportions in the trigger did not significantly vary in this study. (4) Conclusions: Inhalation exposure to aerosol generating sprays should consider the spatial uncertainty in terms of the estimation of short-term exposure.

The basal transcriptional activity of the murine Klf10 gene is regulated by the transcriptional factor JunB.

BACKGROUND: Krüppel-like factor 10 (KLF10) belongs to the Sp1-like transcription factor family, which plays an important role in many directions, e.g., cell proliferation, apoptosis, and differentiation. Its 5' upstream regions are conserved across mammalian species. However, the regulatory mechanism has not been elucidated yet. OBJECTIVE: Nonetheless the basal transcriptional regulation mechanisms of these regions are unknown. Here, we characterized it which is indispensable for the basal transcription of the Klf10 gene. METHODS: Seven deletions of 5' upstream DNA fragments from the 10 kb mKlf10 genomic DNA were produced by PCR and cloned into the upstream of the luciferase (Luc) reporter gene in the pGL3 basic plasmid. RESULT: The luciferase reporter assay showed that the DNA sequence at positions from -101 to +68 was required for a principle activity in the promoter of mKlf10 gene, in which transcriptional factor binding motifs, one JunB and two Sp1 sites, are included. Mutations at the sequence of JunB motif, but not at the two Sp1, abrogated the promoter activity completely, suggesting the indispensable role of JunB site for basal transcription of mKlf10 gene. Moreover, electrophoretic mobility and supershift assays (EMSA) uncovered that JunB protein bound to this region specifically. CONCLUSION: Taken together, our study revealed that the JunB but not Sp1 at mKlf10 promoter functions as a positive basic factor for the transcriptional activity of the gene.

Biofilm development of Bacillus siamensis ATKU1 on pristine short chain low-density polyethylene: A case study on microbe-microplastics interaction.

A low-density polyethylene (LDPE) degrading bacterial strain (ATKU1) was isolated (99.86% similar with Bacillus siamensis KCTC 13613T) from a plastic dumping site to study interactions between microplastics (< 5 mm) and microorganisms. The strain was found (by scanning electron microscopy) to form biofilm on the microplastic surface after its interaction with LDPE (avg. Mw~4,000 Da and avg. Mn~1,700 Da) as a sole carbon source. Atomic force microscopy (AFM) showed the biofilm's 3-D developmental patterns and significantly increased Young's modulus of the LDPE surface after microbial treatment. Most of the viable bacteria attached to biofilms rather than media, which suggested their ability to utilize LDPE. Absorption bands of carbonyl, alkenyl, acyl, ester, primary-secondary alcohol, alkene groups and nitric oxides were found on the treated LDPE particles using Fourier-transform infrared spectroscopy. Fourier transform-ion cyclotron resonance mass spectrometry of the media indicated compositional shifts of the compounds after treatment (i.e., increase in the degree of unsaturation and increment in oxygen-to-carbon ratio) and presence of unsaturated hydrocarbons, polyketides, terpenoids, aliphatic/peptides, dicarboxylic acids, lipid-like compounds were hinted. The plastic degrading abilities of Bacillus siamensis ATKU1 suggest its probable application for large scale plastic bioremediation facility.

Phthalate Plasticizers in Children's Products and Estimation of Exposure: Importance of Migration Rate.

Plasticizers are added to diverse consumer products including children's products. Owing to their potential for endocrine disruption, the use of phthalate plasticizers is restricted in many children's products. In this study, exposure to five phthalate esters (dibutylphthalate, di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate, di-isobutyl phthalate, and diisononyl phthalate (DINP)) and an alternative (di-ethylhexyl adipate) was assessed by the use of children's products based on chemical analysis of 3345 products purchased during 2017 and 2019 in Korea. Plasticizers were found above the detection limits in 387 products, and DEHP and DINP were the two most predominantly detected plasticizers. Deterministic and probabilistic estimation of the margin of exposure at a screening level revealed that the use of children's products might be an important risk factor. However, it is also highly likely that the exposure could be overestimated, because the migration rate was estimated based solely on the content of plasticizers in children's products. Chemical migration is a key process determining the absorption of plasticizers from products; thus, further refinements in experimental determination or model estimation of the migration rate are required.

Changes in ecotoxicity of naphthalene and alkylated naphthalenes during photodegradation in water.

Crude oil released into the environment contains many polycyclic aromatic hydrocarbons (PAHs). Alkylated PAHs are more abundant than unsubstituted PAHs and their toxicity is also of serious concern. Among the various physical, chemical, and biological weathering processes of crude oils, photodegradation is one of the most important for determining the environmental fate of oil residues. In this study, the photodegradation rate constants of naphthalene and alkylated naphthalenes were determined under simulated laboratory conditions at different temperature. Changes in the luminescence inhibition of Aliivibrio fischeri, as an indicator of the baseline toxicity, were observed in photodegradation mixtures. The major transformation products were also identified by gas chromatography-mass spectrometry. The photodegradation of naphthalene and the eight alkylated naphthalenes was described well by pseudo-first-order kinetics regardless of experimental temperature. The measured toxicity of the reaction mixtures obtained by photodegradative weathering slightly increased initially and then decreased with further weathering. In all cases, the observed toxicity was greater than accounted for by the parent compounds, indicating that the photodegradation products also contributed significantly to the overall toxicity of the mixtures. The identified photodegradation products were mostly oxygenated compounds such as alcohols, aldehydes, ketones, and quinones, which warrant further investigation.

Inhalation risk assessment of naphthalene emitted from deodorant balls in public toilets.

The inhalation of naphthalene used as deodorant balls in public toilets could be an important cancer risk factor. The atmospheric concentration of naphthalene in public toilets (Cin) was estimated both by a polyurethane foam passive air sampler (PUF-PAS) deployed in nine public toilets in Seoul, Korea and by a steady-state indoor air quality model, including emission estimation using Monte-Carlo simulation. Based on the estimated Cin, cancer risk was also assessed for cleaning workers and the general population. The steady-state Cin estimated using the estimated emission rate, which assumed that air exchange was the only process by which naphthalene was removed, was much greater than the Cin value measured using PUF-PAS in nine public toilets, implying the importance of other removal processes, such as sorption to walls and the garments of visitors, as well as decreased emission rate owing to wetting of the naphthalene ball surface. The 95 percentile values of cancer risk for workers based on the estimation by PUF-PAS was 1.6×10-6 , whereas those for the general public were lower than 1×10-6 . The results suggested that naphthalene deodorant balls in public toilets may be an important cancer risk factor especially for the cleaning workers.