MicroRNA-939 amplifies Staphylococcus aureus-induced matrix metalloproteinase expression in atopic dermatitis.

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. Staphylococcus aureus (S. aureus) colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases. Methods: In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed S. aureus (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) in vitro. Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function in vivo. Results: MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. In vitro studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. In vivo studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of S. aureus and exacerbated S. aureus-induced AD-like skin inflammation. Conclusions: Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.

Interactive effects of microplastics and selected pharmaceuticals on red tilapia: Role of microplastic aging.

The present study used red tilapia (Oreochromis niloticusas) as the model fish to compare the interactive effects between aged and virgin microplastics (MPs) with the antibiotic sulfamethoxazole (SMX) and the ß-blocker propranolol (PRP). To this end, the ultraviolet irradiation was used to simulate the MP aging in the environment. The accumulations of MPs and pharmaceuticals, and changes in enzyme activities and genes expressions in tilapia were also evaluated. Some physical properties of MPs changed during the aging process, reflected by 0.27- and 0.16-fold increases in the specific surface area and average pore volume, respectively. And more carbonyl formation was observed on the surface of aged MPs. Compared to the 14-d coexposure with virgin MPs, the MP aging increased the accumulation of PRP by 82.3% in the brain, whereas decreased the concentration of SMX by 46.1% in the gills. The stress on tilapia caused by the MPs and PRP was alleviated by the aging process, largely related to the lower neurotoxicity and reduced lipid peroxidation damages. However, the coexposure to aged MPs and SMX would result in higher inhibitions of cytochrome P450 enzymes activities. The results of the transcriptomics showed that the MP aging mainly influenced the expression of genes related to the metabolic process, immune system process, and the genetic information process in tilapia under the coexposure to MPs and pharmaceuticals. Collectively, our results suggest that the MP aging could induce complex changes in the interactive effects between MPs and pharmaceuticals on aquatic organisms.

Toxicological effects of nano- and micro-polystyrene plastics on red tilapia: Are larger plastic particles more harmless?

Nanoplastics (NPs) and microplastics (MPs) are a heterogeneous class of pollutants with diverse sizes in aquatic environments. To evaluate the hazardous effects of N/MPs with different sizes, the accumulation, oxidative stress, cytochrome P450 (CYP) enzymes, neurotoxicity, and metabolomics changes were investigated in the red tilapia exposed to three sizes of polystyrene (PS) N/MPs (0.3, 5, and 70 - 90 µm). After 14-d exposures, the largest particles (70 - 90 µm) showed the highest accumulation levels in most cases. Exposures to PS-MPs (5 and 70 - 90 µm) caused a more severe oxidative stress in red tilapia than PS-NPs. The activity of CYP3A-related enzyme was obviously inhibited by PS-NPs, whereas the CYP enzymes in the liver may not be sensitive to MP exposures. In the brain, only 5 µm PS-MPs significantly inhibited the acetylcholinesterase activity. After exposures, the treatments with 0.3, 5, and 70 - 90 µm N/MPs resulted in 31, 40, and 23 significantly differentially expressed metabolites, respectively, in which the pathway of tyrosine metabolism was significantly affected by all the three PS-N/MP exposures. Overall, the PS particles within the µm size posed more severe stress to red tilapia. Our results suggest that the toxicity of N/MPs may not show a simply monotonic negative correlation with their sizes.

Enantioseparation and determination of triazole fungicides in vegetables and fruits by aqueous two-phase extraction coupled with online heart-cutting two-dimensional liquid chromatography.

A novel method for determination of triazole fungicides and their enantiomers in foods was developed by aqueous two-phase extraction (ATPE) coupled with two-dimensional liquid chromatography (2D-LC). With an aqueous two-phase system (ATPS) of ethanol/K2HPO4 as biphasic extractant, the effects of the ATPS composition, extraction temperature and time on extraction yields of triazole fungicides were investigated. Optimum conditions were concluded as follows: ethanol concentration 31% (w/w) and K2HPO4 concentration 21% (w/w), extraction temperature 60 °C, extraction time 21 min. Based on reversed-phase separation systems, a 2D-LC was constructed by optimizing chromatographic conditions and online heart-cutting procedures. As a result, eight triazole fungicides and their enantiomers were separated respectively on C18 and cellulose-tris (3,5-dimethylphenylcarbamate) stationary phases, revealing good linear relationship in the range of 0.1218-30.06 µg/mL (R2 ≥ 0.9984). The detection limits and recoveries were 0.03113-0.3525 µg/mL and 71.57-107.8%, respectively. The ATPE-2D-LC method was successfully applied to chiral analysis of triazole fungicides in fruits and vegetables.