Photodegradation enhances the toxic effect of anthracene on skin.

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.

Cellular response of keratinocytes to the entry and accumulation of nanoplastic particles.

Plastic accumulation in the environment is rapidly increasing, and nanoplastics (NP), byproducts of environmental weathering of bulk plastic waste, pose a significant public health risk. Particles may enter the human body through many possible routes such as ingestion, inhalation, and skin absorption. However, studies on NP penetration and accumulation in human skin are limited. Loss or reduction of the keratinized skin barrier may enhance the skin penetration of NPs. The present study investigated the entry of NPs into a human skin system modeling skin with compromised barrier functions and cellular responses to the intracellular accumulations of NPs. Two in vitro models were employed to simulate human skin lacking keratinized barriers. The first model was an ex vivo human skin culture with the keratinized dermal layer (stratum corneum) removed. The second model was a 3D keratinocyte/dermal fibroblast cell co-culture model with stratified keratinocytes on the top and a monolayer of skin fibroblast cells co-cultured at the bottom. The penetration and accumulation of the NPs in different cell types were observed using fluorescent microscopy, confocal microscopy, and cryogenic electron microscopy (cryo-EM). The cellular responses of keratinocytes and dermal fibroblast cells to stress induced by NPs stress were measured. The genetic regulatory pathway of keratinocytes to the intracellular NPs was identified using transcript analyses and KEGG pathway analysis. The cellular uptake of NPs by skin cells was confirmed by imaging analyses. Transepidermal transport and penetration of NPs through the skin epidermis were observed. According to the gene expression and pathway analyses, an IL-17 signaling pathway was identified as the trigger for cellular responses to internal NP accumulation in the keratinocytes. The transepidermal NPs were also found in co-cultured dermal fibroblast cells and resulted in a large-scale transition from fibroblast cells to myofibroblast cells with enhanced production of α-smooth muscle actin and pro-Collagen Ia. The upregulation of inflammatory factors and cell activation may result in skin inflammation and ultimately trigger immune responses.

The influence of somatic maturity on the relationship between the triglyceride/high-density lipoprotein ratio and vascular health in children and adolescents with dyslipidemia.

INTRODUCTION: Both the triglyceride to HDL cholesterol (TG/HDL) ratio and timing of pubertal maturation have been identified as independent contributors to the development of atherosclerosis. OBJECTIVE: The purpose of our study was to determine the relationship between the TG/HDL ratio and measures of vascular health in children and adolescents with dyslipidemia stratified by somatic maturity. We hypothesized that somatic maturity would have a significant interaction with TG/HDL ratio and vascular health. METHODS: This was a longitudinal analysis of 120 children and adolescents (age 8-14 years) with dyslipidemia recruited from a pediatric preventive cardiology clinic. At baseline and each follow-up visit, a non-fasting serum lipid panel was collected and vascular health (carotid artery intima--media thickness, pulse wave velocity, augmentation index) was assessed. Peak height velocity (PHV) was calculated at each visit, and participants were stratified into groups by maturity offset (pre-PHV, mid-PHV, post-PHV). A mixed model design permitted baseline and follow-up visits to be classified as discrete data points. RESULTS: Of the n = 235 data points (pre-PHV = 23%, mid-PHV = 19%, and post-PHV = 58%), we identified no significant interaction between TG/HDL ratio, maturity offset, and measures of vascular structure or function. There was also no significant relationship found between TG/HDL and maturity group. Within the mid-pubertal group, there was weak relationship found between TG/HDL and augmentation index. CONCLUSION: Despite the well-described relationship between early pubertal maturation and development of cardiovascular risk factors in adulthood, we found that vascular damage resulting from an elevated TG/HDL ratio is not independently associated with somatic maturity.