Cytotoxicity and Epithelial Barrier Toxicity of Fine Particles from Residential Biomass Pellet Burning.

Rising environmental concerns associated with the domestic use of solid biofuels have driven the search for clean energy alternatives. This study investigated the in vitro toxicological characteristics of PM2.5 emissions from residential biomass pellet burning using the A549 epithelial cell line. The potential of modern pellet applications to reduce PM2.5 emissions was evaluated by considering both mass reduction and toxicity modification. PM2.5 emissions from raw and pelletized biomass combustion reduced cell viability, indicative of acute toxicity, and also protein expression associated with epithelial barrier integrity, implying further systemic toxicity, potentially via an oxidative stress mechanism. Toxicity varied between PM2.5 emissions from raw biomass and pellets, with pelletized straw and wood inducing cytotoxicity by factors of 0.54 and 1.30, and causing epithelial barrier damage by factors of 1.76 and 2.08, respectively, compared to their raw counterparts. Factoring in both mass reduction and toxicity modifications, PM2.5 emissions from pelletized straw and wood dropped to 1.83 and 5.07 g/kg, respectively, from 30.1 to 9.32 g/kg for raw biomass combustion. This study underscores the effectiveness of pelletized biomass, particularly straw pellets, as a sustainable alternative to traditional biofuels and highlights the necessity of considering changes in toxicity when assessing the potential of clean fuels to mitigate emissions of the PM2.5 complex.

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

PDE12 disrupts mitochondrial oxidative phosphorylation and mediates mitochondrial dysfunction to induce oral mucosal epithelial barrier damage in oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic oral mucosal disease. The pathological changes of OSF include epithelial damage and subepithelial matrix fibrosis. This study aimed to reveal the epithelial injury mechanism of OSF. A histopathological method was used to analyze oral mucosal tissue from OSF patients and OSF rats. The expression of PDE12 in the oral epithelium was analyzed by immunohistochemistry. The epithelial-mesenchymal transition (EMT) and tight junction proteins in arecoline-treated HOKs were explored by western blotting. Epithelial leakage was assessed by transepithelial electrical resistance and lucifer yellow permeability. The expression of PDE12 and the mitochondrial morphology, mitochondrial permeability transition pore opening, mitochondrial membrane potential, and mitochondrial reactive oxygen species (mtROS) were evaluated in arecoline-induced HOKs. Oxidative phosphorylation (OXPHOS) complexes and ATP content were also explored in HOKs. The results showed significant overexpression of PDE12 in oral mucosal tissue from OSF patients and rats. PDE12 was also overexpressed and aggregated in mitochondria in arecoline-induced HOKs, resulting in dysfunction of OXPHOS and impaired mitochondrial function. An EMT, disruption of tight junctions with epithelial leakage, and extracellular matrix remodeling were also observed. PDE12 overexpression induced by PDE12 plasmid transfection enhanced the mtROS level and interfered with occludin protein localization in HOKs. Interestingly, knockdown of PDE12 clearly ameliorated arecoline-induced mitochondrial dysfunction and epithelial barrier dysfunction in HOKs. Therefore, we concluded that overexpression of PDE12 impaired mitochondrial OXPHOS and mitochondrial function and subsequently impaired epithelial barrier function, ultimately leading to OSF. We suggest that PDE12 may be a new potential target against OSF.

The last step to achieve barrier damage control.

Heterogeneity characterises inflammatory diseases and different phenotypes and endotypes have been identified. Both innate and adaptive immunity contribute to the immunopathological mechanism of these diseases and barrier damage plays a prominent role triggering type 2 inflammation through the alarmins system, such as anti-Thymic Stromal Lymphopoietin (TSLP). Treatment with anti-TSLP monoclonal antibodies showed efficacy in severe asthma and clinical trials for other eosinophilic diseases are ongoing. The aim of this perspective review is to analyse current advances and future applications of TSLP inhibition to control barrier damage.

Altered Innate Immunity and Damaged Epithelial Integrity in Vaginal Microbial Dysbiosis.

The role of neutrophils relative to vaginal dysbiosis is unclear. We hypothesize that bacterial vaginosis (BV)-associated bacteria may induce the activation and accumulation of mucosal neutrophils within the female reproductive tract (FRT), resulting in epithelial barrier damage. We collected endocervical cytobrushes from women with and without BV and assessed bacteria community type and frequency/functional phenotypes of neutrophils. We performed in vitro whole blood co-cultures with BV-associated bacteria and healthy vaginal commensals and assessed their impact on epithelial integrity using transepithelial electrical resistance. We demonstrated increased neutrophil frequency (p < 0.0001), activation (p < 0.0001), and prolonged lifespan (p < 0.0001) in the cytobrushes from women with non-Lactobacillus dominant (nLD) communities. Our in vitro co-cultures confirmed these results and identified significant barrier damage in the presence of neutrophils and G. vaginalis. Here, we demonstrate that BV-associated bacteria induce neutrophil activation and increase lifespan, potentially causing accumulation in the FRT and epithelial barrier damage.

The influence of air pollution on respiratory microbiome: A link to respiratory disease.

Air pollution is known to trigger and exacerbate many respiratory diseases. The interaction between respiratory microbiome and host plays a significant role in maintaining airway immune homeostasis and health. Emerging evidence has revealed the associations of disturbances in the airway microbiome with air pollution and respiratory disease. However, respiratory microbiome has been an undervalued player in progressions of respiratory disease caused by air pollution. In this review, we summarize the current research advances with respect to the effects of air pollution on respiratory microbiome, then discuss the underlying mechanisms of air pollution induction of dysbiosis in respiratory microbiota and its links to respiratory diseases. This work may be helpful to deepening understanding the relationships between exposure, microbiome and airway disease and discovering new preventive and therapeutic strategies for air pollution-mediated respiratory disease.

Navy and black bean supplementation attenuates colitis-associated inflammation and colonic epithelial damage.

The enriched levels of nondigestible fermentable carbohydrates and phenolic compounds found in common beans can exert immunomodulatory effects within the colon that improve gut health and mitigate the severity of colitis-associated inflammatory pathology. Prior to acute colitis onset, C57Bl/6 mice were prefed isocaloric 20% cooked navy bean (NB) or black bean (BB) diets for 3 weeks and switched to control basal diet (BD) 24 h prior to colitis induction via 5-day exposure to dextran sodium sulfate (2% w/v in drinking water)+3 days of fresh water. The severity of the acute colitis phenotype was attenuated by bean prefeeding, evidenced by reduced colon tissue inflammatory transcription factor activation (NFκB, STAT3) and inflammatory mediator levels in the colon (IL-1ß, IL-6, IL-18 and MCP-1) and serum (TNFα, IL-6, IL-1ß, MCP-1) versus BD (P≤.05). Additionally, biomarkers of enhanced wound repair responses were increased by bean prefeeding including colon tissue protein levels of IL-22, IL-27 and activated (i.e., GTP-bound) Cdc42 and Rac1 versus BD (P≤.05). mRNA expressions of genes involved in normal colonic epithelial function and the promotion of epithelial barrier integrity, defense and/or restitution and wound closure including MUC1, RELMß, IgA and REG3γ were all increased in NB and BB prefed mice versus BD (P≤.05). Collectively, bean supplementation prior to colitis induction (i.e., mimicking disease relapse) primes the colonic microenvironment to attenuate the severity of the colitis inflammatory phenotype and maintain aspects of epithelial barrier function.