Antimony (Sb) is a metalloid widely used in industrial applications, particularly as a catalyst in the manufacturing of polyethylene terephthalate (PET), which is used in food packaging, water bottles, and household items. Human exposure to Sb may occur via oral, cutaneous, and inhalation routes. Under stress conditions, such as prolonged storage or high temperatures, Sb can migrate from plastic into food or beverages, causing health concerns. Once absorbed in the intestine, Sb compounds interact with biomolecules, potentially affecting physiological functions. Despite Sb classification as a pollutant of priority interest, its toxic molecular mechanisms remain poorly understood. In this study, the effects of very low concentrations of Sb(III) (0.5, 5, 50, 100 nM) were evaluated on human intestinal epithelial Caco-2 cells throughout the whole cell differentiation period, simulating continuous human exposure. Sb(III) exposure affected the intestinal epithelial barrier, activating the pro-inflammatory NF-κB signaling pathway and apoptotic cell death, confirmed by Bcl-2, Bax, and Caspase-3 protein levels. Sb(III) exposure triggered oxidative stress, evidenced by increased intracellular reactive oxygen species (ROS) levels, and endoplasmic reticulum (ER) stress, as indicated by increased levels of key unfolded protein response (UPR) markers (XBP-1s, p-eIF2α, GRP78, ATF4, CHOP). Additionally, Sb-induced ER stress activated SIRT1 signaling pathway. Treatment with ER-stress specific inhibitor tauroursodeoxycholic acid (TUDCA) demonstrated the central role of ER stress in Sb-induced injury. These findings provide new insights in the intestinal epithelial toxicity of low concentrations of Sb(III), suggesting that it would be recommendable to limit Sb use in industrial processes to minimise human health hazards.

Fine particulate matter (PM2.5), a major air pollutant, plays a critical role in exacerbating respiratory diseases such as allergic rhinitis (AR) by inducing inflammation. While its association with AR is well established, the precise mechanisms by which PM2.5 triggers pyroptosis and compromises nasal epithelial barrier integrity remain unclear. This study investigates the role of PM2.5 in promoting pyroptosis in nasal epithelial cells and its contribution to AR pathogenesis. Clinical analysis revealed significantly elevated levels of NLRP3 inflammasomes and pyroptosis-related proteins in the nasal mucosa of patients with AR compared with the control group. In vitro and in vivo experiments further demonstrated that PM2.5 exposure led to a dose-dependent increase in these markers in nasal epithelial cells and AR mouse models. Functional studies using NLRP3 agonists and inhibitors confirmed that PM2.5 induces NLRP3-mediated pyroptosis, resulting in tight junction protein degradation and compromised epithelial barrier integrity. Mechanistic investigations showed that PM2.5 activates the aryl hydrocarbon receptor (AhR) pathway, driving the transcription of cytochrome P450 1A1 (CYP1A1) and increasing reactive oxygen species (ROS) production. Notably, AhR downregulation alleviated PM2.5-induced pyroptosis and epithelial barrier dysfunction, whereas CYP1A1 overexpression reversed these protective effects, highlighting the pivotal role of the AhR/CYP1A1/ROS axis in mediating PM2.5-induced epithelial damage. In conclusion, this study uncovers a novel mechanism by which PM2.5 promotes NLRP3-mediated pyroptosis through the AhR/CYP1A1/ROS signaling pathway, ultimately leading to epithelial barrier disruption and AR exacerbation. These findings highlight the urgent need for strategies to minimize PM2.5 exposure and mitigate its detrimental effects on respiratory health.

Natural polyphenolic extracts have been recognized to reduce the risk of hypertension. Coupled with evidence that gut dysbiosis is tightly linked to the development of hypertension, we hypothesized that modulating gut microbiota may be associated with the benefits of unripe apple polyphenols extract (UAPE). This study aimed to explore the effects of UAPE on hypertension and its complications, while elucidating the underlying mechanisms in spontaneously hypertensive rats (SHR). SHR received either vehicle (ddH2O), captopril (30 mg/kg body weight/day), or low-dose (10 mg/kg body weight/day), middle-dose (50 mg/kg body weight/day), or high-dose (250 mg/kg body weight/day) UAPE by oral gavage daily for 8 weeks. Concurrently, Wistar-Kyoto (WKY) rats received vehicle to serve as normotensive controls. We observed that UAPE offered protective effects against hypertension-induced blood pressure elevation (systolic blood pressure, diastolic blood pressure), glycolipid metabolic disorders (serum lipids, glucose), and renal damage (serum creatinine, renal histopathology) in SHR. Additionally, UAPE exerted gut health benefits via enhancing intestinal barrier integrity (colonic and ileal histopathology, colonic tight junction protein 1 and Occludin mRNA and protein) and mitigating intestinal inflammation (colonic TNFα and IL-6 mRNA) in SHR. Moreover, UAPE effectively alleviated the development of left ventricular hypertrophy (cardiac histopathology, echocardiography) and endothelial dysfunction (serum endothelial nitric oxide synthase, endothelin-1), both critical markers of hypertensive progression. Mechanistically, the anti-inflammatory effects of UAPE may be linked to the colonic inhibition of the HMGB1-TLR4-NF-κB signaling pathway (mRNA and protein for colonic HMGB1, TLR4, and P-P65) in SHR. Notably, UAPE elevated microbial richness and diversity, normalizing the Firmicutes/Bacteroidetes ratio. Besides, UAPE increased the beneficial bacteria linked to healthy states, including Intestinimonas_butyriciproducens, Lactobacillus_intestinalis, Ruminiclostridium, Oscillibacter_sp., and Bifidobacterium, reduced the harmful bacteria related to hypertension, upregulated health-promoting microbial function, and elevated the concentrations of gut microbiota-derived short chain fatty acids, including acetic acid and butyric acid, in SHR. Collectively, these observations support the antihypertensive effects of UAPE in the SHR model, highlighting the intimate link between UAPE, gut microbiota, and hypertension. Our findings provide novel insights into the UAPE-mediated improvements in hypertension and its complications, which may be intricately linked to the modulation of the microbiota-gut axis.

Our understanding of the airway epithelium's role in driving asthma pathogenesis has evolved over time. From being regarded primarily as a physical barrier that could be damaged via inflammation, the epithelium is now known to actively contribute to asthma development through interactions with the immune system. The airway epithelium contains multiple cell types with specialized functions spanning barrier action, mucociliary clearance, immune cell recruitment, and maintenance of tissue homeostasis. Environmental insults may cause direct or indirect injury to the epithelium leading to impaired barrier function, epithelial remodelling, and increased release of inflammatory mediators. In severe asthma, the epithelial barrier repair process is inhibited and the response to insults is exaggerated, driving downstream inflammation. Genetic and epigenetic mechanisms also maintain dysregulation of the epithelial barrier, adding to disease chronicity. Here, we review the role of the airway epithelium in severe asthma and how targeting the epithelium can contribute to asthma treatment.

Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer, has raised concerns due to its potential role in exacerbating food allergy through chronic human exposure. The study aimed to investigate the potential effects of DEHP on ovalbumin (OVA)-induced food allergy and elucidate the underlying mechanisms related to intestinal barrier homeostasis. In OVA-sensitized BALB/c mice, DEHP exposure significantly exacerbated allergic responses by functioning as an immunoadjuvant, as evidenced by heightened anaphylactic symptoms, elevated serum levels of inflammatory mediators (IgE, IgG, IgG1, IgG2), and increased concentrations of histamine and monocyte chemoattractant protein-1 (MCP-1). Furthermore, DEHP disrupted intestinal barrier integrity and impaired mucin secretion. Administration of high-dose DEHP significantly downregulated the expression of tight junction proteins and mucins. Histopathological analysis revealed goblet cell depletion and diminished mucin production. The results suggest that DEHP exacerbated food allergy through a multifactorial mechanism involving intestinal barrier dysfunction and immune dysregulation. This study establishes a critical association between oral DEHP exposure and food allergy pathogenesis, providing insights into the interplay of environmental pollutants, intestinal immunity, and food allergy manifestation.

Microplastics have emerged as persistent organic pollutants, generating significant concerns regarding their potential toxicity. Nevertheless, the impact of microplastics (MPs) on atherosclerosis in mammals remains uncertain. The present study investigated the deleterious effects of polystyrene microplastics (PS-MPs) on the cardiovascular system of mice. A total of thirty-six male ApoE-/- mice were divided into three groups: a control group and two experimental groups. The experimental groups were subjected to the exposure of 5 μm PS-MPs at concentrations of 1 μg/ml and 10 μg/ml, respectively, for twelve weeks. In parallel, HUVECs were treated with the same concentrations of PS-MPs to assess cellular responses. Our results indicate that PS-MPs exposure increased mouse body weight, disrupted lipid metabolism, and exacerbated atherosclerosis. Additionally, both in vivo and in vitro studies indicate that PS-MPs can induce oxidative stress and promote EndMT through the BMP signaling pathway. These findings suggest that PS-MPs may trigcger atherosclerosis and cardiovascular toxicity by activating the BMP pathway and driving EndMT via oxidative stress. In summary, this study elucidates the cardiovascular deleterious effects induced by PS-MPs in mice, providing new insights into the toxicity of PS-MPs in mammalian organisms.

Aflatoxin contamination poses a significant challenge to global food safety, public health, and agricultural sustainability. Traditional methods for mitigating aflatoxins, such as chemical and physical detoxification techniques, often raise concerns about environmental harm, nutrient loss, and potential toxicity. In contrast, green-synthesized nanomaterials have emerged as an environmentally friendly and effective solution for controlling aflatoxins. This study explores the potential of green-synthesized nanomaterials for aflatoxin mitigation, focusing on their mechanisms of action, effectiveness, and long-term applicability in agricultural and food safety contexts. A comprehensive review of 116 articles on the latest developments in green nanotechnology was used, focusing on the creation, characterization, and application of nanoparticles, including silver, zinc oxide, titanium dioxide, and iron-based nanomaterials. Green nanoparticles reduce aflatoxin load primarily through their antioxidant properties, which neutralize oxidative stress, and their high adsorption capacity, which binds aflatoxins and reduces their bioavailability. Photocatalytic degradation, adsorption, and enzymatic detoxification were also evaluated. The results indicate that green-synthesized nanoparticles exhibit high efficacy, biocompatibility, and minimal environmental impact, especially when compared to traditional detoxification methods. However, challenges such as nanoparticle stability, large-scale production, regulatory issues, and potential long-term toxicity still require further investigation. To advance this field, future studies should focus on refining green synthesis processes, enhancing nanoparticle stability, and exploring the integration of nanotechnology with biosensors and smart packaging for real-time aflatoxin monitoring. By advancing these sustainable technologies, this research aims to contribute to the development of effective and safe methods for aflatoxin mitigation, thereby supporting global food security, public health, and environmental sustainability.

This study aims to investigate the influence of ozone exposure on mouse corneas and human corneal epithelial cells (HCEC) to better understand its impact on corneal health and the underlying molecular mechanisms. Elevated cyclic ozone exposure was applied to both mouse corneas and HCECs to assess its effects on corneal structure and cellular response. Ozone exposure induced corneal stromal thinning (27.88 %), increased epithelial thickness (22.44 %), and disrupted epithelial barrier function. Inflammatory responses and nitrative stress, marked by inflammatory cell infiltration and heightened 3-nitrotyrosine levels, coupled with the upregulation of NLRP3, caspase-1 were observed in mice cornea. Additionally, ozone exposure induced diminished cell viability, nitrative stress, and activation of the NLRP3/caspase-1/GSDMD pathway in HCECs, which were mitigated by anti-nitration agent MnTMPyP treatment. In summary, the study elucidated the mechanisms underlying ozone-induced corneal toxicity, highlighting nitrative stress and NLRP3 inflammasome-mediated pyroptosis. These findings suggest the importance of minimizing ozone exposure and also provide potential therapeutic strategies targeting nitrative stress and inflammasome activation to prevent ozone-related tissue damage.

Gastric ulcer is a multifaceted ailment of multiple causes and is chronic warranting the discovery of remedies to alleviate its symptoms and severity. Pancratium maritimum L. is recognized for its several health benefits, although its potential against gastric ulcers has yet to be reported.

This study reports on the effects of P. maritimum L. whole plant (PM-EtOH) ethanol extract at a dose of 25, 50, and 100 mg/kg body weight orally for managing ethanol-induced peptic ulcer in rats. The anti-ulceration capacity of PM-EtOH was determined against ethanol (EtOH)-induced rats via biochemical, histological, immunohistochemical, and western blotting assays. The profiling of the bioactive metabolites in P. maritimum extract was based on Ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-qTOF-MS/MS) analysis. Following PM-EtOH treated group, the gastric glutathione (GSH) level dropped in the ulcer group receiving ethanol was restored to normal levels. Additionally, following PM-EtOH, elevated malondialdehyde (MDA) content in the stomach tissues diminished. PM-EtOH treated group displayed recovery and comparable morphology compared with normal group, concurrent with lower levels of Tumor Necrosis Factor α (TNF-α), MyD88, and NLRP3, along with low expression of Nuclear Factor kappa β (NF-кβ) and high-mobility group box protein 1 (HMGB1) proteins. Immune-histochemicals of caspase-3 and toll-like receptors-4 (TLR-4) showed their normalization. These findings imply that PM-EtOH exerts a protective effect on rat stomach damage that has yet to be further tested in clinical trials for treatment of stomach ulcers. Phytochemical profiling of PM-EtOH via UHPLC-ESI-qTOF-MS/MS led to the identification of 84 metabolites belonging to amino acids, organic acids, phenolic acids, alkaloids, flavonoids, and fatty acids to likely mediate for the observed effects.

These outcomes provided evidence for the potential of PM-EtOH in gastric ulcers management.

Multiple pesticide residues in the diet can be ingested through the intestine; however, the interactions affecting intestinal health remain unclear. Histopathological analysis of mouse intestines revealed synergistic damage in those exposed to a binary mixture of abamectin, fluazinam, and spirodiclofen. The combined exposure to fluazinam and spirodiclofen resulted in a 73.35 % reduction in the expression level of the tight junction protein claudin-1 in Caco-2 cells. The studies on the transport in Caco-2 cells revealed that the combined exposure to abamectin and spirodiclofen resulted in transport amounts that were 5.37 and 19.98 times greater than those observed with individual exposures, respectively. The transporter inhibitors and molecular docking analysis indicated that competitive inhibition of the breast cancer resistance protein (BCRP) led to decreased pesticide efflux. Therefore, the disruption of the intestinal barrier caused by the interaction of pesticide mixtures warrants attention when evaluating the safety of various pesticide residues.

Recently, the "epithelial barrier hypothesis" has been proposed as a key factor in the development of allergic diseases, such as food allergies. Harmful environmental factors can damage epithelial barriers, with detrimental effects on the host immune response and on the local microbial equilibrium, resulting in chronic mucosal inflammation that perpetuates the dysfunction of the epithelial barrier. The increased epithelial permeability allows allergens to access the submucosae, leading to an imbalance between type 1 T-helper (Th1) and type 2 T-helper (Th2) inflammation, with a predominant Th2 response that is the key factor in food allergy development. In this article on the state of the art, we review scientific evidence on the "epithelial barrier hypothesis", with a focus on food allergies. We describe how loss of integrity of the skin and intestinal epithelial barrier and modifications in gut microbiota composition can contribute to local inflammatory changes and immunological unbalance that can lead to the development of food allergies.

Air pollution poses significant risks to human health, but its impact on gastrointestinal (GI) health remains underexplored. This study assesses the long-term effects of air pollution on GI diseases using data from the China Health and Retirement Longitudinal Study (CHARLS).

This nationwide cohort study utilized CHARLS data from participants recruited in 2011, followed by surveys in 2013, 2015, 2018, and 2020. Long-term exposure to PM2.5, PM10, SO2, NO2, CO, and O3 was assessed using geocoded residential addresses linked to air quality data. Cox proportional hazards models and subgroup interaction analyses were used to evaluate associations between pollutants and GI disease incidence, adjusting for demographic and behavioral confounders.

The incidence of GI disease was 21.4% among participants. Long-term exposure to PM2.5 (HR = 1.38, 95% CI: 1.33-1.44), PM10 (HR = 1.31, 95% CI: 1.26-1.36), SO2 (HR = 1.74, 95% CI: 1.68-1.81), NO2 (HR = 1.21, 95% CI: 1.17-1.25), CO (HR = 1.48, 95% CI: 1.42-1.54), and O3 (HR = 0.56, 95% CI: 0.54-0.59) was significantly associated with GI disease. Interaction analyses showed that the effects of pollutants varied by region, residence, smoking, and alcohol use. Urban residents and those living in specific regions experienced stronger associations, likely due to higher pollution levels and different environmental factors. Smokers and alcohol users were also more susceptible to the adverse effects of pollutants.

Long-term exposure to multiple air pollutants increases the risk of GI diseases, while ozone may potentially offer some protective effects. Public health measures to reduce air pollution, especially in urban areas, and to protect high-risk groups are urgently needed.

Many environmental, genetic, and epigenetic variables are considered to influence the evolution of cow's milk allergy (CMA). The gastro-intestinal microbiota may play a direct role in or inhibit tolerance development. In this study, we planned to evaluate the presence of previously identified risk factors for microbiota composition. This study used a cross-sectional electronic survey in Turkiye, utilizing a national convenience sample of 270 children with CMA, as reported by their caregivers, and 2154 healthy controls. We developed a web-based questionnaire to gather information on pregnancy and maternal-related factors, delivery mode, feeding patterns, antibiotic use, and the presence of pets in the home. The risk factors affecting CMA were maternal age (OR 0.897; 0.862-0.934, p < 0.01), presence of maternal allergic disorders (OR 3.070; 1.891-4.983, p < 0.001) and in both parents (OR 3.831; 1.202-12.210, p < 0.001), maternal weight at conception (OR 1.016; 1.003-1.030, p < 0.05), maternal weight gain during pregnancy (OR 1.033; 1.012-1.056, p < 0.01), (absence of a) pet at home (OR 1.394; 1.003-1.938, p < 0.05), intrapartum antibiotic use (OR 1.469; 1.092-1.975, p < 0.05), antibiotic use during the first 6 months of life (OR 1.933; 1.306-2.863, p < 0.001), and number of householders (OR 0.794; 0.650-0.969, p < 0.05).

In addition to allergic disorders in parents, maternal weight and weight gain during pregnancy, intrapartum and first 6 months of life antibiotic use, and the presence of pets at home were found to be microbiota-related risk factors in children with CMA. Potential strategies related to microbiota composition may contribute positively to the disease's development and progression.

• The gut microbiome contributes to the development of cow milk allergy, and disrupted microbiota maturation during the first year of life appears to be common in pediatric food allergies. • Factors that influence an infant's microbiota within the first 1000 days and the relationship between these factors and microbiota may enhance allergy diagnosis, prevention, and treatment.

• Besides parental allergy disorders, maternal weight and weight gain during pregnancy, antibiotic use during intrapartum and first six months of life, and the presence of pets at home were identified as microbiota-related risk factors in children with CMA.

Platelet-activating factor (PAF) mediates nasal congestion and rhinorrhea by affecting vascular permeability, but the underlying mechanisms remain unclear. Here, we sought to explore the effect of PAF on the nasal epithelial barrier in chronic rhinosinusitis with nasal polyps (CRSwNP).

Human nasal epithelial cells (hNECs) were pre-treated with Apafant, a PAF receptor (PAFR) inhibitor, or MCC950, an NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor, before PAF stimulation. The nasal epithelial barrier function was assessed by measuring the transepithelial electrical resistance (TER) and sodium fluorescein flux. Additionally, the expression of mRNAs and proteins of tight junctions were assessed.

PAF significantly decreased TER and enhanced the fluorescein flux permeability in air-liquid interface cultures of hNECs, while also downregulating the expression of ZO-1, occludin, claudin-1, and claudin-4. However, the disruptive effect of PAF on the nasal epithelial barrier was attenuated by MCC950, but not by Apafant. Furthermore, MCC950 inhibited PAF-induced NLRP3 activation and its downstream molecules, including caspase-1, ASC, interleukin (IL)-1β, and IL-18.

Our findings indicate that PAF has the potential to disrupt the nasal epithelial barrier in CRSwNP and may be linked to NLRP3 activation, while PAFR is not essential for this process. This discovery helps to explain why PAFR antagonists are ineffective in blocking PAF-mediated inflammation in clinical settings.

Ceramides in the stratum corneum (SC) are important for epidermal barrier function. We previously developed a synthetic pseudo-ceramide for medical (SPCM)-containing steroid cream [SPCM (+)]. This cream forms films on the skin surface and exerts anti-inflammatory effects through steroids. However, the preventive effects of this cream on the disruption of the skin barrier remained unclear. Therefore, in this study, we aimed to evaluate the protective role of SPCM (+) cream against atopic dermatitis (AD)-associated protease allergens on the skin in recovery from barrier-broken skin. We used three-dimensional (3D) skin and mouse models of disrupted skin barriers to evaluate the protective effect of SPCM (+) cream against V8 protease produced by Staphylococcus aureus. In NC/Nga mice with itching caused by living mites, SPCM (+) cream was repeatedly applied once a day for 2 weeks, and scratching behaviour was assessed every week using the MicroAct system. In the 3D skin model, the SPCM (+) cream directly blocked SC degradation by V8 protease of S. aureus and suppressed the expression of interleukin-36 gamma. The application of SPCM (+) cream to mite-parasitised mice suppressed scratching, reduced elevated activity of skin proteases, and inhibited upregulation of thymic stromal lymphopoietin. These beneficial effects of SPCM (+) cream were not observed with steroid creams without SPCM. These results suggest that the SPCM (+) cream is effective in relieving inflammation and itching by protecting the skin from proteases and allergens through its lamellar structure. This cream may be a promising treatment option for skin barrier disorders including AD and xerosis.

Our objectives were to explore epidermal barrier defects in dogs with atopic dermatitis and to determine whether the defects are genetically determined or secondary to skin inflammation. First, the expression of filaggrin, corneodesmosin, and claudin1, analyzed using indirect immunofluorescence in skin biopsies collected from 32 healthy and 32 dogs with atopic dermatitis, was weaker in the atopic skin (P = .003). Second, primary keratinocytes of atopic dogs and healthy dogs were used to produce 3-dimensional reconstructed canine epidermis. The expression of the same proteins was analyzed using indirect immunofluorescence, immunoblotting, and RT-qPCR, whereas reconstructed canine epidermis morphology was investigated by transmission electron microscopy, and the barrier was investigated by functional assays. Next, inflammatory cytokines (IL-4, IL-13, IL-31, and TNFα) were added to the culture medium. The morphology, protein expression, and barrier function of the reconstructed canine epidermis were similar whether produced with keratinocytes from healthy dogs or dogs with atopy. Addition of inflammatory cytokines impaired the protein expression and epidermal barrier of the 2 types of reconstructed canine epidermis equally. To conclude, the reduced expression of epidermal barrier proteins observed in vivo was not reproduced in vitro unless cytokines were used, suggesting that it is induced by the inflammatory milieu.

Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.

Allergic disease is caused by the activation of allergen-specific CD4+ type-2 T follicular helper cells (Tfh2) and T helper 2 (Th2) effector cells that secrete the cytokines IL-4, IL-5, IL-9, and IL-13 upon allergen encounter, thereby inducing IgE production by B cells and tissue inflammation. While it is accepted that the priming and differentiation of naïve CD4+ T cells into Th2 requires allergen presentation by type 2 dendritic cells (DC2s), the underlying signals remain unidentified. In this review we focus on the interaction between allergen-presenting DC2s and naïve CD4+ T cells in lymph node (LN), and the potential mechanisms by which DC2s might instruct Th2 differentiation. We outline recent advances in characterizing DC2 development and heterogeneity. We review mechanisms of allergen sensing and current proposed mechanisms of Th2 differentiation, with specific consideration of the role of DC2s and how they might contribute to each mechanism. Finally, we assess recent publications reporting a detailed analysis of DC-T cell interactions in LNs and how they support Th2 differentiation. Together, these studies are starting to shape our understanding of this key initial step of the allergic immune response.

Despite advances in our understanding of their diagnosis and treatment, pediatric allergies impose substantial burdens on affected children, families, and healthcare systems. Further, the prevalence of allergic diseases has dramatically increased over the past half-century, leading to additional concerns and concerted efforts to identify the origins, potential predictors and preventions, and therapies of allergic diseases. Together with the increase in allergic diseases, changes in lifestyle and early-life environmental influences have corresponded with changes in colonization patterns of the infant gut microbiome. The gut microbiome plays a key role in developing the immune system, thus greatly influencing the development of allergic disease. In this review, we specifically highlight the importance of the proper maturation and composition of the gut microbiome as an essential step in healthy child development or disease progression. By exploring the intertwined development of the immune system and microbiome across pediatric allergic diseases, we provide insights into potential novel strategies for their prevention and management.

As a new type of pollutant, the harm caused by microplastics (MPs) to organisms has been the research focus. Recently, the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products, such as takeout. The damage to the digestive system has attracted increasing attention. We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system. The mechanism may be related to the toxic effects of MPs themselves, interactions with various substances in the biological body, and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption. Based on the toxicity mechanism of MPs, we propose specific suggestions to provide a theoretical reference for the government and relevant departments.

According to the gene-environment interactions concept, the mechanism of health impairment can be explained by genetic factors, environmental factors, or their interaction. Physical and mental health effects resulting from environmental exposure may be classified either as toxicity, immune response, and allergic reaction. Moreover, despite the already established therapeutic approaches to bronchial asthma and decreasing mortality due to bronchial asthma, patients with difficult and severe asthma are increasing in number. This review outlines recent topics in the field of allergies, focusing on asthma.

Living environment-derived pollutants and their involvement in the pathogenesis of asthma and its exacerbation, referred to here as an exposome concept, comprises the three domains of internal, specific external, and general external. Living environment-derived pollutants include exposure to pollutants in workplaces, climate change, air pollution, microplastics, tobacco smoke, biodiversity change and loss, changing dietary habits, and the microbiome. These are associated with the modernization, urbanization, and globalization of human society. Although many novel compounds are currently available, their harmful health effects, such as allergy, are not thoroughly understood. Hence, the means to mitigate these are unknown. Dietary changes from a traditional diet rich in fish to a Western-style diet are considered critical environmental factors and therefore, associated with an increased prevalence of allergies. Cytokines, including thymic stromal lymphopoietin, IL-25, and IL-33, released from the airway epithelium in response to various triggers (exposure to diverse environmental factors) are known as alarmins. Anti-alarmin antibodies are a promising therapeutic approach against severe and difficult allergic disorders. Collaboration between hospitals and clinics and occupational and clinical medicine is imperative for treating and managing severe asthma. In addition to avoiding environmental exposure, understanding the pathogenesis and exacerbation of asthma is essential for future research in the field of allergy and immunotoxicology.

Co-exposure to ground-level ozone (O3) and fine particles (PM2.5, ≤ 2.5 µm in diameter) has become a primary scenario for air pollution exposure of urbanites in China. Recent studies have suggested a synergistic effect of PM2.5 and O3 on induction of lung inflammatory injury. However, the underlying mechanisms for respiratory toxicity induced by this co-exposure have not been adequately elucidated. In this study, a realistic exposure was based to set up the co-exposure condition of an animal model. Specifically, eighty male C57BL/6 mice (10 months old) were randomly divided into four groups: control, O3, PM2.5 and co-exposure (O3 + PM2.5). Mice in the co-exposure group breathed O3 and orally inhaled PM2.5 suspension. The scenario for O3 exposure was 0.6 ppm, 4 h/d, for 30 consecutive days while that for PM2.5 exposure was oral inhalation of PM2.5 suspension (5.6 mg/kg bw) once every other day and 4 h prior to O3 exposure. After last exposure, bronchoalveolar lavage fluids (BALF) were collected for inflammatory biomarker measurement, 16S rRNA sequencing and metabolite profiling. Lung tissues were processed for histological examination. The results demonstrated that co-exposure to O3 and PM2.5 exacerbated the pathological changes and inflammatory response induced by O3 or PM2.5. Further studies revealed that co-exposure to O3 and PM2.5 increased the abundance of Prevotella in the airways and caused more severe metabolic disorders compared to O3 or PM2.5 exposure. Spearman correlation analysis demonstrated correlations among airway microbiota dysbiosis, metabolic disorder, inflammation, and pathological alterations induced by co-exposure to O3 and PM2.5. In summary, co-exposure to O3 and PM2.5 worsens airway inflammatory injury, possibly through interrelated airway microbiota dysbiosis and metabolic disorder.

The gut barrier encompasses several interactive, physical, and functional components, such as the gut microbiota, the mucus layer, the epithelial layer and the gut mucosal immunity. All these contribute to homeostasis in a well-regulated manner. Nevertheless, this frail balance might be disrupted for instance by westernized dietary habits, infections, pollution or exposure to antibiotics, thus diminishing protective immunity and leading to the onset of chronic diseases. Several gaps of knowledge still exist as regards this multi-level interaction. In this review we aim to summarize current evidence linking food antigens, microbiota and gut permeability interference in diverse disease conditions such as celiac disease (CeD), non-celiac wheat sensitivity (NCWS), food allergies (FA), eosinophilic gastrointestinal disorder (EOGID) and irritable bowel syndrome (IBS). Specific food elimination diets are recommended for CeD, NCWS, FA and in some cases for EOGID. Undoubtfully, each of these conditions is very different and quite unique, albeit food antigens/compounds, intestinal permeability and specific microbiota signatures orchestrate immune response and decide clinical outcomes for all of them.

Eosinophilic esophagitis (EoE) is a food- and aeroallergen-driven, type 2-mediated chronic inflammation that develops in genetically predisposed individuals with an impaired esophageal epithelial barrier. How pollutants, including detergents, the esophageal microbiome, immunity, and genetics trigger the multifaceted pathophysiology of EoE is not clear.

This review summarizes and discusses recent findings concerning the possible contribution of the environment/exposome, the esophageal microbiome, genetics, immunity, and epithelial barrier integrity to developing esophageal type 2 inflammation and fibrosis in EoE. After summarizing the current literature, we formulate research questions that we consider relevant to EoE.

The anticipated progress in preclinical EoE animal models, primary cell culture technologies, sequencing technologies, and clinical trials, driven by academic research and the pharmaceutical industry, is poised to revolutionize our understanding of EoE. These advancements may uncover novel pathways that can be targeted for EoE treatment, inspiring hope for improved patient quality of life.

Skin is continuously exposed to environmental external and internal factors, including psychological stress (PS). PS has been reported to trigger different dermatoses such as psoriasis, atopic dermatitis, vitiligo, alopecia areata, and acne through the release of cortisol and epinephrine.

To clinically explore PS-induced measurable skin aging signs in subjects with moderate versus mild chronic PS, and to investigate the effect of chronic PS on DNA damage at cellular level.

In vitro stress tests with cortisol and epinephrine, and with cortisol only on extracellular matrix (ECM) synthesis, as well as on normal human skin fibroblast and keratinocyte functioning, including skin barrier and wound healing were performed.

Moderately stressed subjects in the context of the clinical study had a significantly decreased antioxidant potential and impacted skin barrier integrity, as well as significantly increased signs of microrelief alterations (skin texture and fine lines) reaching an increased severity of about 32.9%. At a cellular level, DNA integrity, ECM synthesis, wound healing, and skin barrier parameters were impacted by increased stress hormone levels.

The clinical exploratory studies presented herewith, as well as the study of cell functioning under stress, have provided evidence that chronic PS significantly affects skin homeostasis and triggers skin aging.

The skin microbiome undergoes constant exposure to solar radiation (SR), with its effects on health well-documented. However, understanding SR's influence on host-associated skin commensals remains nascent. This review surveys existing knowledge on SR's impact on the skin microbiome and proposes innovative sun protection methods that safeguard both skin integrity and microbiome balance. A team of skin photodamage specialists conducted a comprehensive review of 122 articles sourced from PubMed and Research Gateway. Key terms included skin microbiome, photoprotection, photodamage, skin cancer, ultraviolet radiation, solar radiation, skin commensals, skin protection, and pre/probiotics. Experts offered insights into novel sun protection products designed not only to shield the skin but also to mitigate SR's effects on the skin microbiome. Existing literature on SR's influence on the skin microbiome is limited. SR exposure can alter microbiome composition, potentially leading to dysbiosis, compromised skin barrier function, and immune system activation. Current sun protection methods generally overlook microbiome considerations. Tailored sun protection products that prioritize both skin and microbiome health may offer enhanced defense against SR-induced skin conditions. By safeguarding both skin and microbiota, these specialized products could mitigate dysbiosis risks associated with SR exposure, bolstering skin defense mechanisms and reducing the likelihood of SR-mediated skin issues.

The indiscriminate use of plastic products and their inappropriate management and disposal contribute to the increasing presence and accumulation of this material in all environmental zones. The chemical properties of plastics and their resistance to natural degradation lead over time to the production of microplastics (MPs) and nanoplastics, which are dispersed in soil, water, and air and can be absorbed by plants, including those grown for food. In agriculture, MPs can come from many sources (mulch film, tractor tires, compost, fertilizers, and pesticides). The possible effects of this type of pollution on living organisms, especially humans, increase the need to carry out studies to assess occupational exposure in agriculture. It would also be desirable to promote alternative materials to plastic and sustainable agronomic practices to protect the safety and health of agricultural workers.

Butyric acid (BA) can potentially enhance the function of the intestinal barrier. However, the mechanisms by which BA protects the intestinal mucosal barrier remain to be elucidated. Given that the Ras homolog gene family, member A (RhoA)/Rho-associated kinase 2 (ROCK2)/Myosin light chain kinase (MLCK) signaling pathway is crucial for maintaining the permeability of the intestinal epithelium, we further investigated whether BA exerts a protective effect on epithelial barrier function by inhibiting this pathway in LPS-induced Caco2 cells. First, we aimed to identify the optimal treatment time and concentration for BA and Lipopolysaccharide (LPS) through a CCK-8 assay. We subsequently measured Trans-epithelial electrical resistance (TEER), FITC-Dextran 4 kDa (FD-4) flux, and the mRNA expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, along their protein expression levels, and average fluorescence intensity following immunofluorescence staining. We then applied the ROCK2 inhibitor Y-27632 and reevaluated the TEER, FD-4 flux, and mRNA, and protein expression of ZO-1, Occludin, RhoA, ROCK2, and MLCK, as well as their distribution in Caco2 cells. The optimal treatment conditions were determined to be 0.2 mmol/L BA and 5 μg/mL LPS for 24 hours. Compared with LPS treatment alone, BA significantly mitigated the reduction in the TEER, decreased FD-4 flux permeability, increased the mRNA expression of ZO-1 and Occludin, and normalized the distribution of ZO-1 and Occludin in Caco2 cells. Furthermore, BA inhibited the expression of RhoA, ROCK2, and MLCK, and normalized their localization within Caco2 cells. Following treatment with Y-27632, the epithelial barrier function, along with the mRNA and protein expression and distribution of ZO-1 and Occludin were further normalized upon inhibition of the pathway. These findings contribute to a deeper understanding of the potential mechanisms through which BA attenuates LPS-induced impairment of the intestinal epithelial barrier.

This research evaluated the protective role of a combined extract of Dioscorea bulbifera and Zingiber officinale (DBZO) against respiratory dysfunction caused by particulate matter (PM2.5) exposure in BALB/c mice. The bioactive compounds identified in the DBZO are catechin, astragalin, 6-gingerol, 8-gingerol, and 6-shogaol. DBZO ameliorated cell viability and reactive oxygen species (ROS) production in PM2.5-stimulated A549 and RPMI 2650 cells. In addition, it significantly alleviated respiratory dysfunction in BALB/c mice exposed to PM2.5. DBZO improved the antioxidant systems in lung tissues by modulating malondialdehyde (MDA) content, as well as levels of reduced glutathione (GSH) and superoxide dismutase (SOD). Likewise, DBZO restored mitochondrial dysfunction by improving ROS levels, mitochondrial membrane potential, and ATP production. Moreover, DBZO modulated the levels of neutrophils, eosinophils, monocytes, and lymphocytes (specifically CD4+, CD8+, and CD4+IL-4+ T cells) in blood and IgE levels in serum. DBZO was shown to regulate the c-Jun N-terminal kinase (JNK) pathway, nuclear factor kappa B (NF-κB) pathway, and transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) pathway. Histopathological observation indicated that DBZO mitigates the increase in alveolar septal thickness. These findings indicate that DBZO is a promising natural agent for improving respiratory health.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

Since the 1960s, more than 350,000 new chemicals have been introduced into the lives of humans and domestic animals. Many of them have become part of modern life and some are affecting nature as pollutants. Yet, our comprehension of their potential health risks for both humans and animals remains partial. The "epithelial barrier theory" suggests that genetic predisposition and exposure to diverse factors damaging the epithelial barriers contribute to the emergence of allergic and autoimmune conditions. Impaired epithelial barriers, microbial dysbiosis, and tissue inflammation have been observed in a high number of mucosal inflammatory, autoimmune and neuropsychiatric diseases, many of which showed increased prevalence in the last decades. Pets, especially cats and dogs, share living spaces with humans and are exposed to household cleaners, personal care products, air pollutants, and microplastics. The utilisation of cosmetic products and food additives for pets is on the rise, unfortunately, accompanied by less rigorous safety regulations than those governing human products. In this review, we explore the implications of disruptions in epithelial barriers on the well-being of companion animals, drawing comparisons with humans, and endeavour to elucidate the spectrum of diseases that afflict them. In addition, future research areas with the interconnectedness of human, animal, and environmental well-being are highlighted in line with the "One Health" concept.

Particulate matter 2.5 (PM2.5) exposure is intricately linked to asthma exacerbations. Damage to the airway epithelial barrier function serves as an initiating factor for asthma attacks and worsening symptoms. In recent years, numerous exosomal microRNAs (miRNAs) have emerged as potential biomarkers for diagnosing asthma. However, the mechanisms by which PM2.5-induced exosomes exacerbate asthma remain unclear. This study aims to investigate the role of exosomal miR-129-2-3p in regulating airway epithelial cell barrier function, its potential targets, and signaling pathways involved in PM2.5-induced aggravation of asthma. In this study, miR-129-2-3p is highly expressed in plasma exosomes from patients with asthma, mouse lung tissue and plasma exosomes, and exosomes produced by PM2.5-stimulated 16HBE cells. Moreover, the exposure level of PM2.5 is positively correlated with exosomal miR-129-2-3p in plasma in patients with asthma. As the concentration of PM2.5 increases, the synthesis of connexin (ZO-1, occludin, and E-cadherin) is gradually weakened, while the content of inflammatory factors (IL-6, IL-8, and TNF-α) is notably upregulated in PM2.5 exacerbated asthmatic mice. PM2.5-induced exosomes can decrease the level of connexin, enhance cell permeability and promote the secretion of inflammatory factors in 16HBE cells. TIAM1, a specific target gene for miR-129-2-3p, regulates the synthesis of connexin. Exosomal miR-129-2-3p exacerbates airway epithelial barrier dysfunction by targeted inhibition of the TIAM1/RAC1/PAK1 signaling pathway in PM2.5 aggravated asthma. In contrast, blocking miR-129-2-3p may be an alternative approach to therapeutic intervention in asthma.

Three-dimensional human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in preclinical investigative dermatology and regulatory toxicology. In this study, we investigated the utility of electrical impedance spectroscopy (EIS) for noninvasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for 7 consecutive days did not impact epidermal morphology, and readouts showed comparable trends with HEEs measured only once. We determined 2 frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9-engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR, or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to proinflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a noninvasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects, and repair.