Ceramide deficiency in the stratum corneum (SC) is a key etiological factor in atopic dermatitis (AD). To clarify the direct role of SC ceramide depletion in impairing SC barrier and water-holding functions and in initiating AD-like skin symptoms and disease-specific molecular alterations, we generated Tg mice overexpressing a mutant form of acid ceramidase (aCDase) under the control of the involucrin promoter, resulting in targeted expression in the upper epidermis. By 3 weeks of age, Tg mice developed noninflammatory, scaly skin characterized by severely compromised barrier integrity and water-holding capacity, along with significantly elevated epidermal aCDase activity and markedly reduced ceramide levels in the SC. Compared to WT controls, Tg mice also exhibited increased epidermal innervation and reduced intraepidermal semaphorin 3a protein levels. Additionally, Tg skin showed substantial changes in the expression of AD-associated biomarkers involved in barrier impairment, pruritus, and Th2 polarization. These included increased levels of Il10, Il17a, S100a7, S100a8, and S100a9 and decreased levels of Cxcl10, Ifng, Il2, Il13, Il33, Sema3a, and Tlr9. Repeated topical application of mite antigens induced allergic responses in Tg mice, but not in WT mice. These responses were characterized by prominent eosinophil infiltration in the dermis and significantly elevated serum IgE levels. Allergen-challenged ear skin from Tg mice also demonstrated significantly increased expression of inflammatory mediators related to AD, including Ccl17, Ccl22, Ccl26, Ccl27, Il3, Il13, Il22, and Il33. These findings establish Tg mice as a pathophysiologically relevant model of AD, presenting key features such as xerotic, pruritic skin, impaired barrier and water-retention functions, and Th2-dominant allergic inflammation. This model provides important insights into ceramide-dependent mechanisms in AD pathogenesis and offers a useful platform for therapeutic development. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Ulcerative colitis (UC) is a chronic, relapsing disease, imposing a heavy disease burden and severely reducing the quality life of patients. This study verified the influence of the PVT1/miR-216a-5p/TLR4 signaling axis on UC. LPS-stimulated RAW264.7 cells were co-cultured with Caco-2 cells to establish an in vitro model. The C57BL/6 J mice induced by 3% DSS were used as an in vivo model. Cytotoxicity and barrier functionwere evaluated in Caco-2 cells. The PVT1, miR-216a-5p, and TLR4 levels were detected by RT-qPCR. ELISA was used to detect the level of pro-inflammatory factors in RAW264.7 supernatant and colon tissue, and the level of ZO-1 and occludin in Caco-2 cells and colon tissue. TEER was used to evaluate the integrity of the barrier function of Caco-2 cells. The targeting relationships between PVT1, miR-216a-5p, and TLR4 were verified by dual-luciferase reporter gene assay. The PVT1 and TLR4 levels were increased, but miR-216a-5p was decreased in the LPS-treated RAW264.7, co-cultured Caco-2, and colon tissue of DSS mice. The pro-inflammatory factor levels in RAW264.7 and colon tissue of DSS mice were increased, while in Caco-2, the cytotoxicity was aggravated, and the integrity of the barrier function was disrupted. The levels of ZO-1 and occludin were decreased in Caco-2 cells and tissue. If the PVT1 expression was inhibited, the results showed an opposite trend. In contrast, inhibition of miR‑216a‑5p reversed the protective effects induced by PVT1 knockdown. The PVT1/miR-216a-5p signaling axis affects the inflammation and intestinal epithelial cell barrier function in UC, which may be a possible therapeutic target for UC.

Neonicotinoid pesticides are highly persistent in the environment, with detection in periodontal blood reported. Although an association with gingival inflammation has been shown, the mechanism related to periodontal disease remains unclear. Previous study found that coxsackievirus and adenovirus receptor (CXADR) is involved in gingival tissue epithelial barrier function, thus the effects of neonicotinoids on CXADR were examined. High performance liquid chromatography of salivary samples from 16 volunteers detected acetamiprid, clothianidin, imidacloprid, and thiamethoxam. Administration of neonicotinoids (Σneonicotinoids) resulted in loss of cell-surface CXADR, which was restored by bafilomycin A1, a lysosomal inhibitor. Using a three-dimensional tissue model of human gingival epithelial cells, Σneonicotinoids were found to increase permeability to lipopolysaccharide (LPS) and peptidoglycan (PGN), which was dependent on CXADR. It is thus suggested that neonicotinoids cause mislocalization of CXADR into lysosomes, leading to gingival barrier function disruption, which allows for bacterial virulence factors to penetrate subepithelial tissues.

Dietary myricetin inhibits AGEs formation during thermal processing in different pattern diets and alleviates AGEs-induced intestinal epithelial damage in Caco-2 cells.

Gallic acid alleviates colitis by restoring intestinal barrier function and enriching butyrate-producing bacteria.

This study aimed to evaluate the toxicological effects of occupational exposure to factory-derived particulate matter (PM2.5) on human skin, emphasizing its role as a potential target organ of environmental toxicants. An epidemiological survey comparing factory and nonfactory workers was conducted by assessing their skin elasticity and color on the neck and forehead. Carbonylated proteins and inflammatory cytokines were quantified using tape stripping, and stratum corneum (SC) desquamation and cell area were analyzed using Brilliant Green staining. In addition, HaCaT keratinocytes were exposed to factory-derived PM2.5 (welding fumes), and oxidative stress, inflammation, and barrier function were assessed using gene expression analysis and reporter assays. Factory workers showed reduced dermal elasticity, increased skin redness, elevated levels of carbonylated proteins and inflammatory cytokines (IFN-γ and CXCL10), and enhanced SC desquamation with smaller cell areas. Consistently, invitro exposure of HaCaT keratinocytes to PM2.5 induced oxidative stress (activation of the antioxidant response element pathway), inflammatory responses (nuclear factor kappa B activation), and suggested barrier impairment. These findings reveal that chronic occupational exposure to welding fumes impairs skin structure and function through oxidative stress, inflammation, and barrier disruption, highlighting the skin as a relevant target organ in occupational toxicology.

Two low molecular weight-polysaccharides isolated from the edible fungus Sarcodon imbricatus: Isolation, characterization, immunomodulatory and intestinal barrier-protective effects.

1,2,3,6-Tetragalloylglucose inhibits hnRNPA2B1/TRAIL Axis to attenuate apoptosis and barrier dysfunction in intestinal epithelial cells: A potential therapeutic avenue for IBD.

Methodological innovations in perfusable vascular networks: Advancing high-density tissue models.

Lactiplantibacillus plantarum WB4201, WB4202, and WB4203 alleviate gut inflammatory responses and strengthen barrier function in LPS-stimulated HT-29 cells.

The main metabolite of fipronil, fipronil sulfone triggers morphological and functional damage to SerW3 cells and dysfunction in blood-testis barrier.

Biosynthetic reuterin improved the intestinal health in pigs.

Low-dose epigallocatechin gallate combined with L-theanine effectively alleviate obesity and metabolic dysfunction-associated steatotic liver disease by remodeling gut homeostasis and avoiding its hepatotoxicity.

HSP72 alleviates heat stress-induced oxidative damage in boar Sertoli cells through modulating the AGE-RAGE/NOX4/NF-κB axis.

Ethnopharmacological basis and combined protection of intestinal barrier function by fucoidan from Sargassum thunbergii and chito-oligosaccharides in DSS-induced colitis.

Transcriptome and alternative splicing analyses uncover immune-centric pathogenesis in periodontitis versus barrier-dysfunction-driven pathogenesis in peri-implantitis.

Effects of dietary allicin supplementation on nutrient digestion and gastrointestinal health of Guizhou black goats.

ALDH2 deficiency increases susceptibility to acetaminophen-induced liver injury through gut microbiota dysbiosis and altered bile acid metabolism.

Elymus nutans transcription factor EnWRKY41 negatively regulates Arabidopsis thaliana drought tolerance by reducing callose deposition via EnGlu1.

Large-leaf yellow tea oligosaccharides alleviate T2DM by promoting GLP-1 secretion and regulating intestinal mucosal barrier.