Objective Phosgene is a highly toxic asphyxiating gas and also an important chemical raw material. Phosgene has been regarded as an environmental pollutant, and the accidental leakage of phosgene in the process of industrial production has posed a serious threat to related occupational groups. Phosgene exposure may lead to acute lung injury (ALI), marked by inflammation, heightened vascular permeability, and potentially life-threatening pulmonary edema. BML-111 is a lipid A4 receptor agonist which is compound with anti-inflammatory and antioxidant properties. The involvement of BML-111 in mitigating phosgene-induced ALI and the underlying mechanisms remain unclear. Methods In this study, we established a phosgene induced ALI rat model, examined the effects of phosgene exposure on lung tissue and bronchoalveolar lavage fluid (BALF) of rats, and evaluated the lung tissue pathology, lung wet weight, lung coefficient and respiratory function of phosgene exposed rats after intervention with BML-111. The levels of pro-inflammatory cytokines and oxidative stress markers were measured in BALF and lung tissue. Results This study showed that BML-111 notably enhanced respiratory function, mitigated ALI severity, and reduced pulmonary edema in phosgene-exposed rats. Mechanistically, these protective effects were attributed to a reduction in pro-inflammatory cytokines and oxidative stress, alongside an enhancement of overall antioxidant capacity. Furthermore, it was found that the activation of ACE2 is a key mechanism through which BML-111 exerts its protection. Conclusion The findings suggest that BML-111 can alleviate phosgene-induced ALI in rats by activating ACE2, thereby inhibiting inflammatory responses and oxidative stress. BML-111 shows promise as a preventive candidate for treating phosgene-induced ALI.

Background Increasing evidence suggests that exposure to fine particulate matter (PM2.5) is associated with an elevated risk of respiratory diseases. However, the precise mechanisms by which PM2.5 influences inflammatory processes in allergic rhinitis (AR) remain insufficiently understood. The STAT pathway has been identified as a critical mediator of immune and inflammatory responses, but its specific role in modulating PM2.5-induced effects in the nasal mucosa of AR remains unclear. This study aims to investigate the impact of PM2.5 on the STAT pathway in the inflammatory response of the nasal mucosa during AR. Methods We analyzed mRNA expression profiles (GSE215411) from the Gene Expression Omnibus (GEO) database to investigate the effects of PM2.5 on human nasal mucosa-derived fibroblasts. Differential expression analysis identified differential expression genes (DEGs), which were visualized through hierarchical clustering and radar plots. GO/KEGG enrichment and Gene Set Enrichment Analysis (GSEA) identified key pathways, focusing on STAT pathway enrichment. Protein–protein interactions (PPIs) within the STAT pathway were analyzed using STRING and Cytoscapedatabase, revealing immune response and cytokine signaling as predominant functional pathways. An AR model, induced by ovalbumin sensitization and whole-body ambient PM2.5 exposure, was utilized to assess the activation of the STAT pathway in nasal mucosal tissue. Results A total of 426 DEGs were identified in human nasal mucosa-derived fibroblasts following PM2.5 exposure, emphasizing STAT pathway involvement. Validation in an AR mouse model confirmed that allergens and PM2.5 activate the STAT pathway, modulating Th2 and inflammatory cytokines. Conclusion PM2.5 exposure significantly activates the STAT pathway in the nasal mucosa of AR, amplifying Th2-related inflammatory cytokine response.

Objective The present study evaluated urinary oxidative stress (OxS) biomarkers to explain the extrapulmonary effect of renal function decline due to subchronic inhalation exposure to particles smaller than 2.5 μm, as well as the correlation of the biomarkers with the particles’ endotoxin content. Materials and methods Adult male Sprague-Dawley rats were exposed to subchronic inhalation of particles smaller than 2.5 μm (8 weeks, 4 days/week, 5 h/day). The control group was exposed to filtered air. MiniVol and HiVol samplers were used to estimate the concentration and collected particles, respectively. Biomarkers were assessed in weekly urine samples harvested by the metabolic cage. The OxS biomarkers assessed were methylglyoxal, non-esterified fatty acids, malondialdehyde, advanced oxidative protein products, arginase, myeloperoxidase, glutathione S-transferase, and gamma-glutamyl transferase, all of which were evaluated by colorimetric assays. Creatinine was evaluated by the Jaffe reaction, and cystatin-C (Cys-C) and neutrophil gelatinase-associated lipocalin-2 were quantified using Luminex technology. Endotoxin content was analyzed with the Limulus Amebocyte Lysate Pyrochrome Chromogenic Test Kit. Results and discussion Subchronic exposure to PM2.5 increased OxS biomarkers in urine. Endotoxin content showed a positive correlation with the urinary OxS biomarkers evaluated. Additionally, urinary OxS biomarkers correlated with creatinine and the early kidney damage biomarkers Cys-C and neutrophil gelatinase-associated lipocalin-2, where the strongest and positive correlations were observed with the latter two biomarkers. Conclusions Inhalation of environmental airborne particles smaller than 2.5 μm increased urinary OxS biomarkers, correlated with endotoxin content and early kidney damage biomarkers. This finding corroborates the extrapulmonary nephrotoxic effect of inhaled particles.

Purpose Airborne pathogen scan penetrate in human respiratory tract and can cause illness. The use of animal models to predict aerosol deposition and study respiratory disease pathophysiology is therefore important for research and a prerequisite to test and study the mechanism of action of treatment. NHPs are relevant animal species for inhalation studies because of their similarities with humans in terms of anatomical structure, respiratory parameters and immune system. Materials and methods The aim of this review is to provide an overview of the state of the art of pathogen aerosol studies performed in non-human primates (NHPs). Herein, we present and discuss the deposition of aerosolized bacteria and viruses. In this review, we present important advantages of using NHPs as model for inhalation studies. Results We demonstrate that deposition in the respiratory tract is not only a function of aerosol size but also the technique of administration influences the biological activity and site of aerosol deposition. Finally, we observe an influence of a region of pathogen deposition in the respiratory tract on the development of the pathophysiological effect in NHPs. Conclusion The wide range of methods used for the delivery of pathogento NHP respiratory airways is associated with varying doses and deposition profiles in the airways.

Objectives To evaluate potential airborne asbestos exposures during brake maintenance and repair activities on a P&H overhead crane, and during subsequent handling of the mechanic’s clothing. Methods Personal (n = 27) and area (n = 61) airborne fiber concentrations were measured during brake tests, removal, hand sanding, compressed air use, removal and reattachment of chrysotile-containing brake linings, and reinstallation of the brake linings. The mechanic’s clothing was used to measure potential exposure during clothes handling. Results All brake linings contained between 19.9% to 52.4% chrysotile asbestos. No amphibole fibers were detected in any bulk or airborne samples. The average full-shift airborne chrysotile concentration was 0.035 f/cc (PCM-equivalent asbestos-specific fibers, or PCME). Average task-based personal air samples collected during brake maintenance, sanding, compressed air use, and brake lining removal tasks ranged from 0 to 0.48 f/cc (PCME). The calculated 30-minute time-weighted average (TWA) airborne chrysotile concentration associated with 5-15 minutes of clothes handling was 0–0.035 f/cc PCME. Conclusion The results indicated that personal and area TWA fiber concentrations measured during all crane brake maintenance and clothes handling tasks were below the current OSHA 8-h TWA Permissible Exposure Limit for asbestos of 0.1 f/cc. Further, no airborne asbestos fibers were measured during routine brake maintenance tasks following the manufacturer’s maintenance manual procedures. All short-term airborne chrysotile concentrations measured during non-routine tasks were below the current 30-minute OSHA excursion limit for asbestos of 1 f/cc. This study adds to the available data regarding chrysotile exposure potential during maintenance on overhead cranes.

Objective The present work concentrated on validating whether sinomenine alleviates bleomycin (BLM)-induced pulmonary fibrosis, inflammation, and oxidative stress. Methods A rat model of pulmonary fibrosis was constructed through intratracheal injection with 5 mg/kg BLM, and the effects of 30 mg/kg sinomenine on pulmonary inflammation, fibrosis, apoptosis, and 4-hydroxynonenal density were evaluated by hematoxylin and eosin staining, Masson’s trichrome staining, TUNEL staining, and immunohistochemistry. Hydroxyproline content and concentrations of inflammatory cytokines and oxidative stress markers were detected using corresponding kits. MRC-5 cells were treated with 10 ng/ml PDGF, and the effects of 1 mM sinomenine on cell proliferation were assessed by EdU assays. The mRNA expression of inflammatory cytokines and the protein levels of collagens, fibrosis markers, and key markers involved in the TLR4/NLRP3/TGFβ signaling were tested with RT-qPCR and immunoblotting analysis. Results Sinomenine attenuated pulmonary fibrosis and inflammation while reducing hydroxyproline content and the protein expression of collagens and fibrosis markers in BLM-induced pulmonary fibrosis rats. Sinomenine reduced apoptosis in lung samples of BLM-challenged rats by increasing Bcl-2 and reducing Bax and cleaved caspase-3 protein expression. In addition, sinomenine alleviated inflammatory response and oxidative stress in rats with pulmonary fibrosis induced by BLM. Moreover, sinomenine inhibited the TLR4/NLRP3/TGFβ signaling pathway in lung tissues of BLM-stimulated rats. Furthermore, TLR4 inhibitor, TAK-242, attenuated PDGF-induced fibroblast proliferation and collagen synthesis in MRC-5 cells. Conclusion Sinomenine attenuates BLM-caused pulmonary fibrosis, inflammation, and oxidative stress by inhibiting the TLR4/NLRP3/TGFβ signaling, indicating that sinomenine might become a therapeutic candidate to treat pulmonary fibrosis.

Objective The purpose of these studies was to investigate the uptake of atrazine across the nasal mucosa to determine whether direct transport to the brain through the olfactory epithelium is likely to occur. These studies were undertaken to provide important new information about the potential for the enhanced neurotoxicity of herbicides following nasal inhalation. Materials and Methods Transport of atrazine from aqueous solution and from commercial atrazine-containing herbicide products was assessed using excised nasal mucosal tissues. The permeation rate and the role of membrane transporters in the uptake of atrazine across the nasal mucosa were also investigated. Histological examination of the nasal tissues was conducted to assess the effects of commercial atrazine-containing products on nasal tissue morphology. Results Atrazine showed high flux across both nasal respiratory and olfactory tissues, and efflux transporters were found to play an essential role in limiting its uptake at low exposure concentrations. Commercial atrazine-containing herbicide products showed remarkably high transfer across the nasal tissues, and histological evaluation showed significant changes in the morphology of the nasal epithelium following exposure to the herbicide products. Discussion Lipophilic herbicides such as atrazine can freely permeate across the nasal mucosa despite the activity of efflux transporters. The adjuvant compounds in commercial herbicide products disrupt the nasal mucosa’s epithelial barrier, resulting in even greater atrazine permeation across the tissues. The properties of the herbicide itself and those of the formulated products play crucial roles in the potential for the enhanced neurotoxicity of herbicides following nasal inhalation.

Introduction Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual’s work history including working as a “mucker” at a specific “industrial” talc mine. Methods Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed. Discussions/Conclusions The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a “non-commercial” type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.

Sugarcane is the most widely cultivated crop in the world, with equatorial developing nations performing most of this agriculture. Burning sugarcane is a common practice to facilitate harvest, producing extremely high volumes of respirable particulate matter in the process. These emissions are known to have deleterious effects on agricultural workers and nearby communities, but the extent of this exposure and potential toxicity remain poorly characterized. As the epidemicof chronic kidney disease of an unknown etiology (CKDu) and its associated mortality continue to increase along with respiratory distress, there is an urgent need to investigate the causes, determine viable interventions to mitigate disease andimprove outcomes for groups experiencing disproportionate impact. The goal of this review is to establish the state of available literature, summarize what is known in terms of human health risk, and provide recommendations for what areas should be prioritized in research.

Objective Armed conflicts result in the release of toxic chemicals into the surrounding environment and civilians are commonly exposed to these toxicants. This paper reviews the evidence on civilian exposure to toxic chemicals, including but not limited to inhaled toxic substances, in post-World War II armed conflicts, and proposes a framework for the implementation of long-term surveillance programs for these populations. Materials and Methods Four databases of peer-reviewed health articles were searched for all English-language articles with a primary focus on toxic chemical exposures among civilians in armed conflicts since World War II. The review was supplemented substantially by the gray literature. Results In the 66 articles that met the inclusion criteria, the authors categorized the chemical toxicants to which civilians have been exposed in modern armed conflicts as ubiquitous (e.g. smoke, dust, and munitions components present in all conflicts) or particular agents (e.g. specific chemical agents used in a few conflicts). While most studies focused on particular agents, the vast majority of civilians are in fact exposed to ubiquitous agents both in the acute conflict phase and through persistent environmental exposures after the cessation of hostilities. Discussion/Conclusion There is a dearth of research concerning civilian exposures to toxic chemicals during armed conflicts. In line with principles of equity, justice, and accountability, robust research and surveillance programs are urgently needed to document exposures and provide ongoing assessments and any necessary treatment for these long-ignored populations, most of whom live in the Global South.