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Metal oxide nanoparticles (MONP/s) induce DNA damage, which is influenced by their physicochemical properties. In this study, the high-throughput CometChip and micronucleus (MicroFlow) assays were used to investigate DNA and chromosomal damage in mouse lung epithelial cells induced by nano and bulk sizes of zinc oxide, copper oxide, manganese oxide, nickel oxide, aluminum oxide, cerium oxide, titanium dioxide, and iron oxide. Ionic forms of MONPs were also included. The study evaluated the impact of solubility, surface coating, and particle size on response. Correlation analysis showed that solubility in the cell culture medium was positively associated with response in both assays, with the nano form showing the same or higher response than larger particles. A subtle reduction in DNA damage response was observed post-exposure to some surface-coated MONPs. The observed difference in genotoxicity highlighted the mechanistic differences in the MONP-induced response, possibly influenced by both particle stability and chemical composition. The results highlight that combinations of properties influence response to MONPs and that solubility alone, while playing an important role, is not enough to explain the observed toxicity. The results have implications on the potential application of read-across strategies in support of human health risk assessment of MONPs. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors have profoundly changed cancer treatment, improving the prognosis of many oncologic patients. However, despite the good efficacy of these drugs, their mechanism of action, which involves the activation of the immune system, can lead to immune-related adverse events, which may affect almost all organs. Pulmonary adverse events are relatively common, and potentially life-threatening complications may occur. The diagnosis is challenging due to the wide and non-specific spectrum of clinical and radiological manifestations. The role of the radiologist is to recognize and diagnose pulmonary immune-related adverse events, possibly even in the early stages, to estimate their extent and guide patients' management. [ABSTRACT FROM AUTHOR]

Precision-cut lung slices (PCLS) are a suitable model for analyzing the acetylcholinesterase (AChE) activity and subsequent effects after exposure to organophosphorus (OP) compounds. In this study, the AChE activity was determined in intact PCLS for the first time. Since the current standard therapy for OP poisoning (atropine + oxime + benzodiazepine) lacks efficiency, reliable models to study novel therapeutic substances are needed. Models should depict pathophysiological mechanisms and help to evaluate the beneficial effects of new therapeutics. Here PCLS were exposed to three organophosphorus nerve agents (OPNAs): sarin (GB), cyclosarin (GF), and VX. They were then treated with three reactivators: HI-6, obidoxime (OBI), and a non-oxime (NOX-6). The endpoints investigated in this study were the AChE activity and the airway area (AA) change. OPNA exposure led to very low residual AChE activities. Depending on the reactivator properties different AChE reactivation results were measured. GB-inhibited PCLS-AChE was reactivated best, followed by VX and GF. To substantiate these findings and to understand the connection between the molecular and the functional levels in a more profound way the results were correlated to the AA changes. These investigations underline the importance of reactivator use and point to the possibilities for future improvements in the treatment of OPNA-exposed victims. • Acetylcholinesterase (AChE) activity determination in precision-cut lung slices (PCLS): Use of PCLS as an ex vivo model. • Comprehensive OPNA exposure and reactivation study: Exposure of PCLS to GB, GF, and VX, followed by reactivation with HI-6, OBI, and aNOX-6. • AChE reactivation results: Revealing varying reactivation efficiencies for different nerve agents: GB > VX > GF. • Correlation of molecular and functional levels: Correlating AChE activities with airway area (AA) changes. [ABSTRACT FROM AUTHOR]

This study explores the impact of silymarin, a potent natural flavonoid with robust antioxidant properties, on paclitaxel-induced lung injury. Paclitaxel, a widely used chemotherapeutic agent for cancer, is known for its adverse effects on various organs. The research involved four groups: the Control group (6 animals) received oral saline; the SIL group (6 animals) received 200 mg/kg silymarin orally for 10 days; the PAX group (6 animals) received intraperitoneal paclitaxel (2 mg/kg) for 5 days; and the PAX+SIL group (6 animals) received both treatments. All groups were sacrificed on the 10th day. Histopathological analysis revealed pathological changes in the lung tissue of the PAX group. Immunopositivity of Bax, iNOS, Nf-kB, and IL-6 antibodies was higher in the PAX group compared to silymarin-treated groups. Conversely, Bcl-2 and MUC1 immunopositivity was lower in the PAX group but higher in silymarintreated groups. Silymarin administration decreased IL-6, Caspase-3, P2x7 and NFkB p65 immunoreactivity, while increased Bcl-2 immunoreactivity. Protein expression levels of IL-6, Caspase-3, P2x7, and NF-κB were higher in the PAX group but decreased in the PAX+SIL group. Bcl-2 protein expression was lower in the PAX group but higher in the PAX+SIL group. Additionally, antioxidant enzyme levels increased, while MDA levels decreased in the PAX+SIL group. In conclusion, the findings indicate that silymarin effectively ameliorated paclitaxel-induced lung damage, highlighting its potential therapeutic role in mitigating chemotherapy-related side effects. [ABSTRACT FROM AUTHOR]

Introduction: Radiation-induced lung toxicity (RILT) is a major concern in patients who receive radiation to thorax. The purpose of the study was to evaluate the changes of pulmonary function tests (PFTs) in lung carcinoma patients treated with three-dimensional conformal radiation therapy (3-D CRT) and relation RILT with dosimetric and nondosimetric factors. Methods: This was a prospective observational study which included 65 patients of lung carcinoma treated with 3-D CRT. PFTs were assessed before the radiotherapy and at third and sixth month post-radiation therapy. Radiation pneumonitis (RP) was graded according to National Cancer Institute Common Toxicity Criteria (CTCAE) version 4.0. Results: Majority of patients already had poor lung function before commencing the radiotherapy. There was a modest decrease in pulmonary function after radiation therapy with (3-D CRT). Postradiotherapy, at third month, eight patients (12%) and at the sixth month, 16 patients (25%) were observed with Grade II RP. At the third month, the nondosimetric factors, age >65 years (P = 0.027) and pretreatment Diffusion capacity of the Lung for Carbon monoxide (DLCO) 60% (P = 0.03) were significantly related to grade ≥ II Radiation pneumonitis (RP). Among dosimetric factors, mean lung dose ≥20 Gy (P = 0.001) and volume receving 20Gy ≥35% (P = 0.05) were significantly related to grade ≥ II RP. These factors were also related to grade ≥ II RP at the sixth month with a significant P value. Conclusion: There is a progressive decrease in pulmonary function after (3-D CRT) in lung carcinoma patients. The study suggested that the baseline PFT may be utilized for the identification of high-risk patients for RILT before starting the radiotherapy in lung carcinoma. [ABSTRACT FROM AUTHOR]

Thermal spray coating is a process in which molten metal is sprayed onto a surface. Little is known about the health effects associated with these aerosols. Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 hr/d × 4 d) generated during thermal spray coating using different consumables [i.e. stainless-steel wire (PMET731), Ni-based wire (PMET885), Zn-based wire (PMET540)]. Control animals received air. Bronchoalveolar lavage was performed at 4 and 30 d post-exposure to assess lung toxicity. The particles were chain-like agglomerates and similar in size (310–378 nm). Inhalation of PMET885 aerosol caused a significant increase in lung injury and inflammation at both time points. Inhalation of PMET540 aerosol caused a slight but significant increase in lung toxicity at 4 but not 30 d. Exposure to PMET731 aerosol had no effect on lung toxicity. Overall, the lung responses were in the order: PMET885≫PMET540 >PMT731. Following a shorter exposure (25 mg/m3 × 4 h/d × 1d), lung burdens of metals from the different aerosols were determined by ICP-AES at 0, 1, 4 and 30 d post-exposure. Zn was cleared from the lungs at the fastest rate with complete clearance by 4 d post-exposure. Ni, Cr, and Mn had similar rates of clearance as nearly half of the deposited metal was cleared by 4 d. A small but significant percentage of each of these metals persisted in the lungs at 30 d. The pulmonary clearance of Fe was difficult to assess because of inherently high levels of Fe in control lungs. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) is an air pollutant that causes severe lung injury. We investigated the effects of Jujuboside B (JB), a component of Zizyphi Spinosi Semen, on lung toxicity caused by PM2.5, and we identified the mechanism of its protective effect. Lung injury in an animal model was induced by intratracheal administration of a PM2.5 suspension. After 2 days of PM2.5 pretreatment, mice were administered JB via the tail vein three times over a 2-day period. JB significantly reduced the histological lung damage as well as the lung wet/dry weight ratio. JB also considerably reduced PM2.5-induced autophagy dysfunction, apoptosis, inflammatory cytokine levels, and the number of PM2.5-induced lymphocytes in the bronchial alveolar fluid. We conclude that by regulating TLR2, 4-MyD88, and mTOR-autophagy pathways, JB exerts a protective effect on lung injury. Thus, JB can be used as a potential therapeutic agent for PM2.5-induced lung damage. [ABSTRACT FROM AUTHOR]

Background: Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities. Methods: A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values <.05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435. Results: Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r =.952; P <.01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs. Conclusion: Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between high-quality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model. [ABSTRACT FROM AUTHOR]

Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO4) while being treated with Curc or nCurc for 7 days. Cu-triggered lung oxidative stress detected as dysregulation of oxidative/antioxidant markers, a downregulation of Nrf-2/HO-1 signaling, and an increase in the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and intracellular adhesion molecule-1 (ICAM-1). Additionally, it decreased the expression of lung-specific proteins, surfactant protein-C (SP-C), and mucin-1 (MUC-1), induced apoptosis, and caused changes in lung histology. Curc and nCurc alleviated CuSO4-induced lung injury by suppressing oxidative damage and inflammation and activating Nrf-2/HO-1. They also prevented apoptosis and restored the normal expression of SP-C and MUC-1. We concluded that nCurc exhibited superior efficacy compared with Curc in mitigating CuSO4-induced lung injury. This was associated with reduced oxidative stress, inflammation, and apoptotic responses and increased Nrf2/HO-1 signaling and expression of SP-C and MUC-1. [ABSTRACT FROM AUTHOR]

Objective Amiodarone (AD) is a benzofuran derivative, a lipophilic anti-arrhythmic agent structurally similar to thyroxine. It is one of the drugs used against ventricular tachycardia types and atrial fibrillation as a class III potassium channel blocker in the Waughn-Williams drug classification system. Gilaburu (Viburnum opulus L.) is a red, berry-like fruit that is found around the forests in Eurasia and North Africa in the world and most commonly in Kayseri province in our country and has medicinal uses. Many studies has been shown Gilaburu (GL) to high antioxidative, antiproliferative, anti-inflammatory activity with the contain organic acids, phenolic compounds, various amino acids and vitamins. In our study, we aimed to investigated whether gilaburu has a protective effect on the toxicity of amiodarone on rat lung tissue. Material and Methods In the study, 32 male Wistar rats weighing 300-350 g were randomly selected and divided 4 groups as, Control, AD, AD+GL and GL group. In the experiment, 100 mg/kg AD was administered ip to rats for 10 days, and 100 mg/kg gilaburu powdered fruit extract was dissolved in physiological saline by oral gavage. At the end of the experiment, lung tissues were taken and examined by immunohistochemical and histochemical techniques. Results In the histochemical examinations, it was observed that the damage occurred in the lung tissues of the AD group, but the damage decreased in the combined group. As a result of immunohistochemical staining (TNF-a and iNOS), it was observed that the staining was more in the AD group and less in the combined group. Conclusion As a result, we think that gilaburu has a protective effect against lung damage caused by Amiodarone. [ABSTRACT FROM AUTHOR]

Objectives: Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) have shown remarkable clinical activity in patients with non‐small‐cell lung cancer (NSCLC). However, pneumonitis is a serious side effect of ALK TKIs in NSCLC patients. In this meta‐analysis, we aimed to determine the incidence of ALK‐TKI‐associated pneumonitis. Materials and Methods: We searched electronic databases to identify relevant studies published until August 2022. The incidence of pneumonitis was calculated using a fixed‐effects model when no substantial heterogeneity was observed. Otherwise, a random‐effects model was used. Subgroup analyses of different treatment groups were performed. Statistical analyses were conducted using STATA 17.0. Results: Twenty‐six clinical trials involving 4752 patients were eligible for analysis. All‐grade pneumonitis incidence was 2.92% (95% confidence interval [CI]: 1.79%–4.27%), high‐grade (Grade 3–4) pneumonitis incidence was 1.42% (95% CI: 0.84%–2.12%) and Grade 5 pneumonitis incidence was 0.09% (95% CI: 0.00%–0.28%). The subgroup analysis showed that brigatinib was associated with the highest incidence of both all‐grade and high‐grade pneumonitis (7.09% and 3.06%, respectively). ALK TKI treatment after chemotherapy was associated with a higher incidence of all‐grade and high‐grade pneumonitis than first‐line ALK TKI treatment (7.73% vs. 2.26% and 3.64% vs. 1.26%, respectively). Cohorts from Japanese trials had a higher incidence of all‐grade and high‐grade pneumonitis. Conclusion: Our study provides precise data on the incidence of pneumonitis in patients receiving treatment with ALK TKIs. Overall, ALK TKIs have tolerable pulmonary toxicity. Early pneumonitis identification and treatment are required to prevent further deterioration in patients receiving treatment with brigatinib and in those who received prior chemotherapy, particularly in the Japanese population. [ABSTRACT FROM AUTHOR]

Immunotherapy with immune checkpoint inhibitors (ICI) is administered in different cancer types and can lead to a wide range of immune-related adverse events including toxicity in vital organs such as the lungs, the kidneys, and the heart. The main hypothesis suggests an overactivation of the immune cells in the different organs. Whereas immune-related cardiotoxicity is very rare but life threatening, ICI-induced acute kidney injury and pneumonitis are more frequent but in general less severe. Renal toxicity corresponds in more than 90% to an acute tubulo-interstitial nephritis. Checkpoint inhibitors pneumonitis is diagnosed mainly on respiratory symptoms with new radiological features, especially under the form of a cryptogenic organising pneumonia. Cardiotoxicity is predominantly marked by myocarditis but also pericarditis and arrhythmias, among others. Early recognition, temporary or definitive cessation of ICI therapy and rapid initiation of high-dose corticosteroids are the cornerstones of the management, which must to be multidisciplinary in a specialised center. [ABSTRACT FROM AUTHOR]

E-cigarette consumption is under scrutiny by regulatory authorities due to concerns about product toxicity, lack of manufacturing standards, and increasing reports of e-cigarette- or vaping-associated acute lung injury. In vitro studies have demonstrated cytotoxicity, mitochondrial dysfunction, and oxidative stress induced by unflavored e-cigarette aerosols and flavoring additives. However, e-cigarette effects on the complex lung parenchyma remain unclear. Herein, the impact of e-cigarette condensates with or without menthol flavoring on functional, structural, and cellular responses was investigated using mouse precision cut lung slices (PCLS). PCLS were exposed to e-cigarette condensates prepared from aerosolized vehicle, nicotine, nicotine + menthol, and menthol e-fluids at doses from 50 to 500 mM. Doses were normalized to the glycerin content of vehicle. Video-microscopy of PCLS revealed impaired contractile responsiveness of airways to methacholine and dampened ciliary beating following exposure to menthol-containing condensates at concentrations greater than 300 mM. Following 500 mM menthol-containing condensate exposure, epithelial exfoliation in intrabronchial airways was identified in histological sections of PCLS. Measurement of lactate dehydrogenase release, mitochondrial water-soluble-tetrazolium salt-1 conversion, and glutathione content supported earlier findings of nicotine or nicotine + menthol e-cigarette-induced dose-dependent cytotoxicity and oxidative stress responses. Evaluation of PCLS metabolic activity revealed dose-related impairment of mitochondrial oxidative phosphorylation and glycolysis after exposure to menthol-containing condensates. Taken together, these data demonstrate prominent mentholinduced pulmonary toxicity and impairment of essential physiological functions in the lung, which warrants concerns about e-cigarette consumer safety and emphasizes the need for further investigations of molecular mechanisms of toxicity and menthol effects in an experimental model of disease. [ABSTRACT FROM AUTHOR]

Typically used household chemicals comprise numerous compounds. Determining mixture toxicity, as observed when using household chemicals containing multiple substances, is of considerable importance from a regulatory perspective. Upon examining the toxic effects of household chemical mixtures, we observed that hydramethylnon combined with tetramethrin resulted in synergistic toxicity. To determine the unknown toxicity mechanism of hydramethylnon, which carries the risk of inhalation exposure when using household chemicals, we conducted a further investigation using BEAS-2B cells, a human bronchial epithelial cell line. Hydramethylnon-induced cytotoxicity was determined following 24 and 48 h of exposure using the water-soluble tetrazolium 1 and lactate dehydrogenase assays. To elucidate the toxicity mechanism, we utilized flow cytometry and measured the levels of apoptosis-related proteins and caspase activities. Given that hydramethylnon, as an insecticide, disrupts the mitochondrial electron transfer chain, we analyzed the relevant mechanisms, including mitochondrial superoxide levels as well as the mitochondrial membrane potential (MMP). Hydramethylnon dose-dependently induced BEAS-2B cell apoptosis via the intrinsic pathway. Furthermore, it significantly increased mitochondrial superoxide levels and disrupted the MMP. Pre-treatment with a caspase inhibitor (Z -DEVD-FMK) confirmed that hydramethylnon induced caspase-dependent apoptosis. Apoptosis, a key event in the toxicological process of chemicals, can lead to lung diseases, including fibrosis and cancer. The results of the present study suggest a mechanism of toxicity of hydramethrylnon, an organofluorine biocide whose toxicity has been little studied, to the lung epithelium. Considering the potential risks associated with inhalation exposure, these results highlight the need for careful management and regulation of hydramethylnon. • Hydramethylnon can cause lung toxicity by inducing apoptosis of lung epithelial cells. • Hydramethylnon induces mitochondrial superoxide levels and membrane potential loss. • Oxidative stress causes subsequent cellular damage in lung epithelial cells. • Hydramethylnon-induced apoptosis occurs via intrinsic pathway; is caspase-dependent. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities. METHODS: A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values < .05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435. RESULTS: Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r = .952; P < .01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs. CONCLUSION: Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between highquality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT. [ABSTRACT FROM AUTHOR]

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague–Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/m3 × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0–200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days. [ABSTRACT FROM AUTHOR]

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 32 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q10). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl2 in a manner comparable to free SM at the same dosage. [ABSTRACT FROM AUTHOR]

Ultrafine particulate matter with less than 2.5 μm diameter (PM2.5) is an air pollutant that causes severe lung damage. Currently, effective treatment and preventive methods for PM2.5-induced lung damage are limited. Cirsilineol (CSL) is a small natural compound isolated from Artemisia vestita. In this study, the efficacy of CSL on PM2.5-induced lung toxicity was tested, and its mechanism was identified. Lung injury was caused by intratracheal administration of PM2.5 suspension in animal models. Two days after PM2.5 pretreatment, CSL was injected via mouse tail vein for two days. The effects of CSL on PM2.5-induced lung damage, autophagy, apoptosis, and pulmonary inflammation in a mouse model and their mechanisms were investigated. CSL significantly suppressed histological lung damage and lung wet/dry weight proportion. CSL also significantly reduced PM2.5-induced autophagy dysfunction, apoptosis, lymphocyte suppression, and inflammatory cytokine levels in bronchoalveolar fluid (BALF). Furthermore, CSL increased mammalian target of rapamycin (mTOR) phosphorylation and significantly inhibited the expression of Toll-like receptors (TLR) 2 and 4, MyD88, and the autophagy proteins, Beclin1 and LC3II. Thus, CSL exerts protective effects on pulmonary damage by regulating mTOR and TLR2,4–myD88 autophagy pathways. Therefore, CSL can be used as an effective treatment for PM2.5-induced lung damage. [ABSTRACT FROM AUTHOR]

Ga-68 labeled prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in the neovasculature of several nonprostatic benign and malignant pathologies. Docetaxel, a taxane antineoplastic agent, is the mainstay of treatment in castration-resistant prostate cancer and high-volume hormone-sensitive prostate cancer. Although the occurrence of docetaxel-related interstitial lung disease is rare, it may lead to respiratory failure if treatment is delayed. We present a case of metastatic castration-resistant prostate cancer, wherein docetaxel-induced interstitial pneumonitis was detected on Ga-68 PSMA PET/CT after docetaxel administration. [ABSTRACT FROM AUTHOR]

Background and Objective: The study aims to evaluate the histopathological changes, enzymatic alterations, and DNA damage in rat lungs induced by whole-body gamma irradiation as well as evaluation of the protective effect of pycnogenol.Materials and Methods: A hundred adult male rats were equally divided into ten groups including control, four antioxidants, γ-irradiation, four antioxidant + γ-irradiations. This study began the day before radiation treatment and continued for 3 days. The pycnogenol was dissolved 5% dimethyl sulfoxide and then administered orally through a gastric tube at a dose of 37.5 mg/kg, 75 mg/kg, 150 mg/kg, and 300 mg/kg in 24, 48, and 72 h before irradiation. Irradiation was applied with a whole-body irradiation dose of 900 cGy in one fraction. DNA damage, histopathological changes, catalase (CAT), and superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in lung tissue of rats were evaluated 3 days after irradiation.Results: CAT and SOD activities were found to be significantly lower in the irradiation group than control (P < 0.001). CAT and SOD activities were higher in the antioxidant + γ-irradiation group than both irradiation and control groups. MDA levels were significantly higher in the irradiation group compared to control (P < 0.001), whereas MDA levels decreased in the antioxidant + γ-irradiation group compared to the irradiation group. The antioxidant groups were significantly increased comet parameters depend on pycnogenol doses compared to control. The antioxidant + γ-irradiation was decreased comet parameter compared to γ-irradiation. As a result of the histopathologically, the antioxidant groups were different than the control group that in the areas of alveolar sacs and connective tissue areas were seen hemorrhage areas similar to the irradiation group.Conclusion: We demonstrate that 300 mg/kg of pycnogenol might provide significant protection against deleterious effects from whole-body ionizing radiation on the lung tissue. P300+ γ-ray group was significantly reduced radiation-induced lung injury and was possible to observe significantly preservation. [ABSTRACT FROM AUTHOR]

The toxicity of silica nanoparticles (SiNPs) to lung is known. We previously demonstrated that exposure to SiNPs promoted pulmonary impairments, but the precise pathogenesis remains elucidated. Ferroptosis has now been identified as a unique form of oxidative cell death, but whether it participated in SiNPs-induced lung injury remains unclear. In this work, we established a rat model with sub-chronic inhalation exposure of SiNPs via intratracheal instillation, and conducted histopathological examination, iron detection, and ferroptosis-related lipid peroxidation and protein assays. Moreover, we evaluated the effect of SiNPs on epithelial ferroptosis, possible mechanisms using in vitro -cultured human bronchial epithelial cells (16HBE), and also assessed the ensuing impact on fibroblast activation for fibrogenesis. Consequently, fibrotic lesions occurred in the rat lungs, concomitantly by enhanced lipid peroxidation, iron overload, and ferroptosis. Consistently, the in vitro data showed SiNPs triggered oxidative stress and caused the accumulation of lipid peroxides, resulting in ferroptosis. Importantly, the mechanistic investigation revealed miR-21-5p as a key player in the epithelial ferroptotic process induced by SiNPs via targeting GCLM for GSH depletion. Of note, ferrostatin-1 could greatly suppress ferroptosis and alleviate epithelial injury and ensuing fibroblast activation by SiNPs. In conclusion, our findings first revealed SiNPs triggered epithelial ferroptosis through miR-21-5p/GCLM signaling and thereby promoted fibroblast activation for fibrotic lesions, and highlighted the therapeutic potential of inhibiting ferroptosis against lung impairments upon SiNPs exposure. [Display omitted] • Ferroptosis is discovered to be a new form of cell death upon SiNPs exposure. • miR-21-5p was a key player in epithelial ferroptosis by SiNPs via targeting GCLM. • SiNPs-elicited epithelial ferroptosis promoted fibroblast activation. • Anti-ferroptosis strategies maybe a promising strategy for fibrotic lung diseases. [ABSTRACT FROM AUTHOR]

Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide. [Display omitted] • The effects of omarigliptin &/or rosinidin on CPA-lung toxicity were investigated. • Omarigliptin &/or rosinidin restored the antioxidant defenses in the lung tissues. • Omarigliptin &/or rosinidin mitigated inflammation & fibrosis in the lung tissues. • Omarigliptin &/or rosinidin restored autophagy/apoptosis balance in the lung. • Omarigliptin/rosinidin combination was better than each of these agents alone. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7). Materials and methods: Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT-7 particles at target cumulative doses (concentration x time) ranging from 22.5 to 180 (mg/m3)h over a three-day (6 hours/day) period and toxicity and global gene expression profiles were determined in the lungs. Results: MWCNT-7 particles, associated with alveolar macrophages (AMs), were detected in rat lungs following the exposure. Mild to moderate lung pathological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and polymorphonuclear leukocytes (PMNs), intracellular oxidant generation by phagocytes, and levels of cytokines were significantly (p < 0.05) increased in response to exposure to MWCNT-7. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in all the MWCNT-7 exposed rats. Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure. Conclusions: Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) has genotoxic, neurotoxic, and carcinogenic effects. From past to present, various plants or their products have been used for therapeutic purposes such as morin. It was aimed to detect possible protective effects of morin vs ACR‐induced lung toxicity. The rats, treated with ACR alone or with morin for 10 consecutive days, were included in the study. A broad variety of biomarkers related to oxidative stress, apoptosis, autophagy, and inflammatory responses were evaluated. ACR increased malondialdehyde (MDA), tumor necrosis factor‐alpha (TNF‐α), cyclooxygenase‐2 (COX‐2), nuclear factor kappa‐B (NF‐κB), Beclin‐1, IL‐1β, bcl‐2 associated X protein (Bax), caspase‐3, light chain 3‐A (LC3‐A), and light chain 3‐B (LC3‐B) levels but reduced mammalian target of rapamycin (mTOR), b‐cell lymphoma‐2 (Bcl‐2), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione (GSH) in lung tissues. The morin had effects on the level of these molecules in a way that is opposite to ACR. While ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, the morin reduced ACR‐induced lung damage. Practical applications: ACR is a toxic chemical produced by frying, baking, roasting, or grilling foods with high starch content and has genotoxic, neurotoxic, and carcinogenic effects. As an antioxidant compound, the morin is obtained from plants or their products. It was aimed to detect possible protective effects of morin against ACR‐induced lung toxicity. It was detected that ACR‐induced oxidative stress, apoptotic, autophagic, inflammatory responses, and may cause pulmonary dysfunction, but the morin reduced ACR‐induced lung damage. [ABSTRACT FROM AUTHOR]

Nanomaterials (NMs) solve specific problems with remarkable results in several industrial and scientific areas. Among NMs, silver nanoparticles (AgNPs) have been extensively employed as drug carriers, medical diagnostics, energy harvesting devices, sensors, lubricants, and bioremediation. Notably, they have shown excellent antimicrobial, anticancer, and antiviral properties in the biomedical field. The literature analysis shows a selective cytotoxic effect on cancer cells compared to healthy cells, making its potential application in cancer treatment evident, increasing the need to study the potential risk of their use to environmental and human health. A large battery of toxicity models, both in vitro and in vivo, have been established to predict the harmful effects of incorporating AgNPs in these numerous areas or those produced due to involuntary exposure. However, these models often report contradictory results due to their lack of standardization, generating controversy and slowing the advances in nanotoxicology research, fundamentally by generalizing the biological response produced by the AgNP formulations. This review summarizes the last ten years' reports concerning AgNPs' toxicity in cellular respiratory system models (e.g., mono-culture models, co-cultures, 3D cultures, ex vivo and in vivo). In turn, more complex cellular models represent in a better way the physical and chemical barriers of the body; however, results should be used carefully so as not to be misleading. The main objective of this work is to highlight current models with the highest physiological relevance, identifying the opportunity areas of lung nanotoxicology and contributing to the establishment and strengthening of specific regulations regarding health and the environment. [ABSTRACT FROM AUTHOR]

Background: Although rare, taxane-induced interstitial pneumonitis is a well-recognized toxicity following chemotherapy. Data on taxane rechallenge in patients who developed taxane-induced interstitial pneumonitis following chemotherapy are limited. Here, we share our experience of acute interstitial pneumonitis following taxane chemotherapy for breast cancer and its clinical outcome following steroids and subsequent rechallenge with taxanes in selected patients without residual lung abnormalities on imaging following steroid treatment. Objectives: To study the taxane-induced acute interstitial pneumonitis in patients with breast cancer receiving chemotherapy and outcome of taxane rechallenge in these patients. Materials and Methods: Patients with breast cancer who developed taxane-induced acute interstitial pneumonitis following chemotherapy either with paclitaxel or docetaxel were included. Results: Among 1240 patients with breast cancer, who received chemotherapy with either docetaxel or paclitaxel, 41 patients developed taxane-induced acute interstitial lung disease (ILD) during the study period. The interstitial pneumonitis was more seen with docetaxel. Among paclitaxel regimens, weekly schedules showed more cases of ILD than 2 weekly paclitaxel. After steroid pulse/maintenance treatment, complete resolution of lung abnormalities was seen in 76%, but residual interstitial pattern on imaging was noted in 24% of patients. Taxane rechallenge was done in 20 (49%) patients. Agents used were paclitaxel, nab-paclitaxel, or docetaxel. All rechallenged patients received short-course oral steroids for one week following taxane rechallenge as a safety measure. Rechallenge was not done in 51% either due to patient unwillingness for rechallenge (27%) or patient with residual interstitial pattern on imaging (24%). None of the patients experienced any recurrence of pneumonitis or any mortality following taxane rechallenge. Conclusion: Acute interstitial pneumonitis is a well-known toxicity following taxanes in breast cancer and taxane rechallenge is an option in those patients without any residual pneumonitis following steroid pulse/maintenance. We also advise short-course oral steroids for 1 week following taxane rechallenge as a safety measure. We strongly do not recommend rechallenge in patients with residual lung abnormalities after steroids. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer deaths worldwide. In the last decades, an improved knowledge of the molecular pathways that drive malignancy in NSCLC led to the development of specific target agents, TKI (tyrosine kinase inhibitors). For oncogene-negative patients, immune checkpoint inhibitors (ICI) have radically changed the landscape of treatments of advanced NSCLC, improving the survival of patients and their quality of life. Despite the important clinical benefits and the good tolerance, (especially immunotherapy), these new drugs are associated with side effects, including pneumonitis. The incidence of lung toxicity is low but likely to lead to drug withdrawal or death (35% of immune-related fatalities with anti PD1-PDL1). The mechanisms that lead to toxic effects are partially known. Respiratory signs/symptoms and HRTC interstitial patterns are nonspecific, so diagnosis is usually of exclusion. The management of drug-related pneumonitis is based on severity: according to grade, clinicians should hold the drug (even temporarily) and treat patients with steroids; in severe refractory cases, additional immunosuppressive agents may be considered, but their use is off label. With the extensive use of target therapy and immunotherapy, the reported adverse events are also increasing and early diagnosis and management of toxicities become essential. The role of pulmonologist is crucial for diagnosis and follow up of patients by using pulmonary function tests, blood gas analysis, six minutes walking test (6mWT). A decrease in diffusing capacity for carbon monoxide (DlCO) may reflect interstitial and parenchymal damage after treatment, like a progressive decline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC): patients with impaired lung capacity before treatment seem to have higher risk (interstitial lung diseases or COPD). Clinicians should pay close attention to these toxic events and we suppose that a multidisciplinary management, with organ-specialists involvement, may improve patients outcome during lung cancer therapy. [ABSTRACT FROM AUTHOR]

Pulmonary toxicity is documented in long‐term survivors of allogeneic BMT. No studies have specifically evaluated late pulmonary symptomatology in these patients. 85 long‐term pediatric survivors were sent a validated questionnaire of pulmonary symptomatology. Demographic and clinical data were retrospectively collected from the respondents medical records. Response rate was 52.9%. Mean follow‐up post‐BMT of those who responded was 12.3 years. Mean pulmonary symptom scores were low (0.78). There was no significant difference in symptoms between patients who underwent MA conditioning with or without TBI. These results are reassuring that long‐term survivors of pediatric BMT have few respiratory symptoms which do not impact on activities of daily living. [ABSTRACT FROM AUTHOR]

Naja naja snake bite causes thousands of deaths worldwide in a year. N. naja envenomed victims exhibit both local and systemic reactions that potentially lead to death. In clinical practice, pulmonary complications in N. naja envenomation are commonly encountered. However, the molecular mechanisms underlying N. naja venom-induced lung toxicity remain unknown. Here, we reasoned that N. naja venom-induced lung toxicity is prompted by NLRP3 inflammasome and MAPKs activation in mice. Treatment with dimethyl ester of bilirubin (BD1), significantly inhibited the N. naja venom-induced activation of NLRP3 inflammasome and MAPKs both in vivo and in vitro (p < 0.05). Further, BD1 reduced N. naja venom-induced recruitment of inflammatory cells, and hemorrhage in the lung toxicity examined by histopathology. BD1 also diminished N. naja venom-induced local toxicities in paw edema and myotoxicity in mice. Furthermore, BD1 was able to enhance the survival time against N. naja venom-induced mortality in mice. In conclusion, the present data showed that BD1 alleviated N. naja venom-induced lung toxicity by inhibiting NLRP3 inflammasome and MAPKs activation. Small molecule inhibitors that intervene in venom-induced toxicities may have therapeutic applications complementing anti-snake venom. [Display omitted] • Dimethyl ester of bilirubin reversed Naja naja venom induced NLRP3 inflammasome and MAPKs activation. • Dimethyl ester of bilirubin ameliorated Naja naja venom-induced local and systemic toxicities in mice. • Dimethyl ester of bilirubin improved the survival time of Naja naja venom-induced mortality in mice. [ABSTRACT FROM AUTHOR]

Background: bleomycin-induced lung toxicity and oxidative damage by decreasing the deactivating enzyme, genetic vulnerability, and released cytokines of inflammation. Melatonin has a free radical detoxifying effect, coenzyme Q10 has a strong antioxidant effect. Aim of the study: this study aimed to evaluate the possible protective role of melatonin and coenzyme Q10 in bleomycin-induced lung injury in Albino rats. Material and Methods: forty male Albino rats were categorized into five groups; group I (control group), group II (bleomycin group): rats were given a single dose of bleomycin intra-tracheal for inducing lung injury, group III (melatonin group): rats were given melatonin for three weeks after intratracheal installation of bleomycin, group IV (coenzymeQ10 group): rats were given coenzymeQ10 for three weeks after intratracheal installation of bleomycin and group V (combined melatonin and Co Q10 group): rats were given a combination of melatonin and coenzyme Q10for three weeks after induction of bleomycin lung toxicity. Lung tissues were prepared for biochemical, histological and immunohistochemical studies. Results: bleomycin produced a significant increase in the level of malondialdehyde and a significant reduction in glutathione peroxidase activity in lung tissues with loss of normal histological lung architecture, significant elevation in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. In group III melatonin enhanced a significant improvement in the biochemical changes, moderate prevention of histopathological changes in lung tissue with a significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. While, in group IV co enzyme Q10 enhanced non significant improvement in the biochemical changes, mild prevention of histopathological changes and non-significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. Using a combination of both drugs in group V enhanced a significant improvement in the biochemical changes and almost preservation of normal histological architecture of the lung tissue. Conclusion: administration of both melatonin and coenzyme Q10 produced almost a complete recovery of bleomycin induced lung injury. [ABSTRACT FROM AUTHOR]

Background: bleomycin-induced lung toxicity and oxidative damage by decreasing the deactivating enzyme, genetic vulnerability, and released cytokines of inflammation. Melatonin has a free radical detoxifying effect, coenzyme Q10 has a strong antioxidant effect. Aim of the study: this study aimed to evaluate the possible protective role of melatonin and coenzyme Q10 in bleomycin-induced lung injury in Albino rats. Material and Methods: forty male Albino rats were categorized into five groups; group I (control group), group II (bleomycin group): rats were given a single dose of bleomycin intra-tracheal for inducing lung injury, group III (melatonin group): rats were given melatonin for three weeks after intratracheal installation of bleomycin, group IV (coenzyme Q10 group): rats were given coenzyme Q10 for three weeks after intratracheal installation of bleomycin and group V (combined melatonin and Co Q10 group): rats were given a combination of melatonin and coenzyme Q1 0for three weeks after induction of bleomycin lung toxicity. Lung tissues were prepared for biochemical, histological and immunohistochemical studies. Results: bleomycin produced a significant increase in the level of malondialdehyde and a significant reduction in glutathione peroxidase activity in lung tissues with loss of normal histological lung architecture, significant elevation in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. In group III melatonin enhanced a significant improvement in the biochemical changes, moderate prevention of histopathological changes in lung tissue with a significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. While, in group IV co enzyme Q10 enhanced non significant improvement in the biochemical changes, mild prevention of histopathological changes and non-significant reduction in main area percent of collagen fibers deposition and caspase-3 immuno positive expression. Using a combination of both drugs in group V enhanced a significant improvement in the biochemical changes and almost preservation of normal histological architecture of the lung tissue. Conclusion: administration of both melatonin and coenzyme Q10 produced almost a complete recovery of bleomycin induced lung injury. [ABSTRACT FROM AUTHOR]

Human exposure to cellulose nanocrystal (CNC) is possible during the production and/or use of products containing CNC. The objectives of the current study were to determine the lung toxicity of CNC and the underlying molecular mechanisms of the toxicity. Rats were exposed to air or CNC (20 mg/m3, six hours/day, 14 d) by whole-body inhalation and lung toxicity and global gene expression profile were determined. Significant increases in lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and macrophage and neutrophil counts were detected in the bronchoalveolar lavage cells or fluid from the CNC exposed rats. Mild lung histological changes, such as the accumulation of macrophages and neutrophils, were detected in the CNC exposed rats. Gene expression profiling by next generation sequencing identified 531 genes whose expressions were significantly different in the lungs of the CNC exposed rats, compared with the controls. Bioinformatic analysis of the lung gene expression data identified significant enrichment in several biological functions and canonical pathways including those related to inflammation (cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, complement system, acute phase response, leukocyte extravasation signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, and phagosome formation and maturation) and oxidative stress (NRF2-mediated oxidative stress response, production of nitric oxide and reactive oxygen species in macrophages, and free radical scavenging). Our data demonstrated that inhalation exposure of rats to CNC resulted in lung toxicity mediated mainly through the induction of inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

A 33-year-old male patient with a diagnosis of obsessive- compulsive disorder applied to the emergency department with fever, cough, sputum and increasing shortness of breath. A physical examination revealed the patient to be dyspneic and orthopneic. Bilateral rales were present in middle and basal lung areas. Oxygen saturation in room air was 84%. Diffuse parenchymal infiltration and consolidation areas were noted in a posteroanterior chest X-ray and a thorax computerized tomography. The patient's history revealed that the patient used a CPAP machine due to obstructive sleep apnea syndrome and aripiprazole, related to his obsessive-compulsive disorder. The patient was hospitalized in the intensive care unit with a preliminary diagnosis of pneumonia and treated with ceftriaxone 2 gr/day, clarithromycin 2x500 mg and oseltamivir 2x75 mg. Blood and sputum cultures, viral markers and procalcitonin were negative, and so methylprednisolone 40mg/day was started. The patient's clinical condition improved rapidly after treatment with steroids, and he was discharged on the 8th day after admission, with recommendations for ambulatory care. It was learnt that aripiprazole had been added to his treatment for obsessive-compulsive disorder 1 month earlier, and that his complaints had started and gradually intensified 20 days after this change in medication. The patient's clinical picture was assessed as lung toxicity caused by aripiprazole. [ABSTRACT FROM AUTHOR]

Bleomycin is a chemotherapeutic agent that is preferred for the treatment of testicular cancer, lymphoma and some squamous cell carcinomas. Bleomycininduced lung toxicity is a common, but rarely fatal side-effect, and the radiological image of which can be confused with other reasons which makes organizing pneumonia pattern. We report here on the case of a 40-year-old male patient with testicular cancer with bleomycin-induced fatal lung toxicity that was misdiagnosed as Covid-19 pneumonia. The patient suffered subsequent fatal spontaneous pneumomediastinum, pneumothorax, and pulmonary interstitial and subcutaneous emphysema, and died from respiratory failure. [ABSTRACT FROM AUTHOR]

Carbon fibers have excellent physicochemical and electrical properties. Vapor-grown carbon fibers are a type of carbon fibers that have a multi-walled carbon tube structure with a high aspect ratio. The representative vapor-grown carbon fiber, VGCFTMH, is extremely strong and stable and has superior thermal and electrical conductivity. Because some high-aspect-ratio multi-walled carbon nanotubes (MWCNTs) have been reported to have toxic and carcinogenic effects in the lungs of rodents, we performed a 13-week lung toxicity study using VGCFTM-H in comparison with one of MWCNTs, MWNT-7, in rats. Male and female F344 rats were intratracheally administered VGCFTM-H at doses of 0.2, 0.4, and 0.8 mg/kg bw or MWNT-7 at doses of 0.4 and 0.8 mg/kg bw once a week for 8 weeks and then up to week 13 without treatment. The lung burden was equivalent in the VGCFTM-H and MWNT-7 groups; however, the lung weight had increased and the inflammatory and biochemical parameters in the broncho-alveolar lavage fluid and histopathological parameters, including inflammatory cell infiltration, alveolar type II cells proliferation, alveolar fibrosis, pleural fibrosis, lung mesothelium proliferation, and diaphragm fibrosis, were milder in the VGCFTM-H group than in the MWNT-7 group. In addition, the proliferating cell nuclear antigen (PCNA)-positive index in the visceral and pleural mesothelium was significantly higher in the MWNT-7 group than in the controls, but not in the VGCFTM-H group. Thus, the results of this study indicate that the lung and pleural toxicities of VGCFTM-H were less than those of MWNT-7. [ABSTRACT FROM AUTHOR]

Objectives Small molecule tyrosine kinase inhibitors [smTKI, comprising mostly of Janus kinase (JAK) and to a lesser extent, spleen tyrosine kinase (SyK) inhibitors] modulate the cytokine receptor-mediated intracellular signal cascade, and are an effective treatment for autoimmune diseases and malignancies. As smTKI are novel, long-term safety is uncertain. Due to increasing use, characterization of their true adverse event profile is critical. Methods We performed a systematic review and meta-analysis of all published trial data on the pulmonary and serious adverse effects of smTKIs in autoimmune disease. EMBASE, MEDLINE, CENTRAL and Pneumotox databases were searched up to April 2019 for randomized controlled trials, observational studies and post marketing surveillance, comparing any smTKI with placebo or another therapy, or as monotherapy at different doses. Primary outcomes comprised of any respiratory complications including upper and lower respiratory tract infections (URTI, LRTI), influenza, pneumonia, opportunistic respiratory infections, drug-induced interstitial lung disease, pulmonary embolism and lung neoplasm. Results We identified 4667 citations for screening, and selected 319 studies for full text review. Seventy-nine studies were analysed, including 47 randomized controlled trials, 25 observational studies and seven post-marketing surveillance studies, comprising 159 652 participants. There were significantly increased risks of URTI [risk difference (RD) 0.03; 95% CI: 0.01, 0.05; P  = 0.00; 36 studies, 14 724 participants], LRTI (RD 0.01; 95% CI: 0.00, 0.02; P  = 0.02; 24 studies, 12 302 participants), influenza (RD 0.01; 95% CI: 0.00, 0.01; P  = 0.04; 22 studies, 10 684 participants), and pneumonia (RD 0.00; 95% CI: 0.00, 0.01; P  = 0.02; 33 studies, 15 511 participants). No increased risk was found for other respiratory complications, including pulmonary embolism. Conclusion SmTKI increases the risk of non-opportunistic respiratory infections compared with placebo. The risk of any serious pulmonary adverse events is low. [ABSTRACT FROM AUTHOR]

• Heart dose volume parameters predicted the risk on cardiac toxicity. • Lung dose volume parameters predicted the risk on pulmonary toxicity. • Overall survival was associated with pulmonary but not cardiac toxicity. • Overall survival was best predicted by lung dose in amongst clinical parameters. The aim of this study was to evaluate which clinical and treatment-related factors are associated with heart and lung toxicity in oesophageal cancer patients treated with chemoradiation (CRT). The secondary objective was to analyse whether these toxicities are associated with overall survival (OS). The study population consisted of a retrospective cohort of 216 oesophageal cancer patients treated with curative CRT. Clinical and treatment related factors were analysed for OS and new pulmonary and cardiac events by multivariable regression analyses. The effect of these toxicities on OS was assessed by Kaplan Meyer analyses. Multivariable analysis revealed that pulmonary toxicity was best predicted by the mean lung dose. Cardiac complications were diverse; the most frequently occurring complication was pericardial effusion. Several cardiac dose parameters correlated with this endpoint. Patients developing radiation pneumonitis had significantly worse OS than patients without radiation pneumonitis, while no difference was observed in OS between patients with and without pericardial effusion. OS was best predicted by the V45 of the lung and tumour stage. None of the cardiac dose parameters predicted OS in multivariable analyses. Cardiac dose volume parameters predicted the risk of pericardial effusion and pulmonary dose volume parameters predicted the risk of radiation pneumonitis. However, in this patient cohort, pulmonary DVH parameters (V45) were more important for OS than cardiac DVH parameters. These results suggest that reducing the cardiac dose at the expense of the dose to the lungs might not always be a good strategy in oesophageal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is the standard care for inoperable early stage non‐small cell lung cancer (NSCLC). The purpose of our study was to investigate whether a prediction model based on cone‐beam CT (CBCT) plus pretreatment CT radiomics features could improve the prediction of tumor control and lung toxicity after SBRT in comparison to a model based on pretreatment CT radiomics features alone. Methods: A total of 34 cases of stage I NSCLC patients who received SBRT were included in the study. The pretreatment planning CT and serial CBCT radiomics features were analyzed using the imaging biomarker explorer (IBEX) software platform. Multivariate logistic regression was conducted for the association between progression‐free survival (PFS), lung toxicity and features. The predictive capabilities of the models based on CBCT and CT features were compared using receiver operating characteristic (ROC) curves. Results: Five CBCT features and two planning CT features were correlated with disease progression. Six CBCT features and two planning CT features were related to lung injury. The ROC curves indicated that the model based on the CBCT plus planning CT features might be better than the model based on the planning CT features in predicting lung injury. The other ROC curves indicated that the model based on the planning CT features was similar to the model based on the CBCT plus planning CT features in predicting disease progression. Conclusions: Both pretreatment CT and CBCT radiomics features could predict disease progression and lung injury. A model with CBCT plus pretreatment CT radiomics features might improve the prediction of lung toxicity in comparison with a model with pretreatment CT features alone. Key points: Significant findings of the study: A model with cone‐beam CT radiomics features plus pre‐treatment CT radiomics features might improve the prediction of lung toxicity after SBRT in stage I NSCLC patients.What this study adds: In the prediction of PFS and lung toxicity in early‐stage NSCLC patients treated with SBRT, CBCT radiomics could be another effective method. [ABSTRACT FROM AUTHOR]

Lead (Pb) is recognized as the first heavy metal of the top six toxic air pollutants threatening human health and the second hazardous substance. Pb exposure is associated with lung impairment and high incidences of lung cancer. Nuclear factor kappa B (NF-κB) and aryl hydrocarbon receptor (AhR) signaling pathways are known to be expressed and play an important role in the lung. However, the link between Pb lung toxicity and NF-κB and/or AhR pathways remains unclear. This study was established to explore the role of NF-κB and AhR modulation in Pb-induced lung toxicity in human lung cancer A549 cells. In the current study, treatment of A549 cells with Pb significantly induced cell apoptosis as evidenced by increasing a) the percentage of cells underwent apoptosis determined by flow cytometry and b) p53 mRNA level. Pb treatment induced oxidative stress by a) increasing the formation of reactive oxygen species and b) decreasing GSTA1 mRNA levels. The toxic effects of Pb on the lung was associated with significant increases in NF-κB and AhR levels which was accompanied with increases in downstream targets genes, iNOS and CYP1A1, respectively. Inhibition of NF-κB or AhR either chemically using resveratrol or genetically using small interfering RNA (siRNA) significantly rescued A549 cells from Pb-mediated lung toxicity. The results clearly indicate that Pb-mediated lung toxicities are NF-κB and AhR-dependent mechanism. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to investigate occupational exposure to carbon fibers impregnated with epoxy resins (carbon fiber reinforced [CFR]) in workers at an airplane fuselage section construction plant, by environmental and biological monitoring. Materials and methods: Determination of airborne CFR was done by environmental sampling with active samplers, 11 of which were stationary and 19 personal samplings. The subsequent analyses were performed in the scanning electron microscope fitted with an X-ray microanalysis system (SEM-EDXA). Biological monitoring was carried out by determining CFR in exhaled breath condensate (EBC) collected from 19 male workers who wore personal environmental samplers (exposed workers) and from 10 male workers at the same factory who had no occupational exposure to CFR (internal controls). CFR analysis was done by SEM, applying the method used for determining asbestos fibers in aqueous samples. Results: The airborne CFR concentrations were found to be significantly higher (p = 0.03) at personal samplings (median value 7.01 ff/L, range 1.24–11.16 ff/L) than stationary samplings (median value 1.93 ff/L, range 0.55–10.09 ff/L). The aerodynamic diameters calculated starting from the length and geometric diameter of the sampled CFRs were always higher than 20 µm. CFR was not found in any of the EBC samples collected from the exposed workers and controls. Conclusions: Despite the evidence of occupational exposure to low concentrations of CFR, the absence of such fibers in the EBC in the exposed workers confirms their non-respirability, as expected based on their aerodynamic diameter. [ABSTRACT FROM AUTHOR]

One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2–10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5–3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9–9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. "Recent Era" patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to "Early Era". Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing. [ABSTRACT FROM AUTHOR]

• Airborne PVA and PHA NP induce less lung and liver toxicity than airborne PVC NP. • Airborne PVA, PHA and PVC NP induce airway microbiota and serum metabolome changes. • Foodborne PVA and PHA NP induce less liver toxicity than foodborne PVC NP. • Foodborne PVA, PHA and PVC NP cause gut microbiota and serum metabolome alterations. Nanoplastics (NP) are emerging pollutants in the environment. Bio-based materials are attracting increasing scientific attention as their application may alleviate the environmental pollution caused by conventional plastics. However, their hazardous potentials still need to be investigated. In this study, multi-omics approaches were carried out to explore and compare the conventional polyvinyl chloride (PVC), bio-based polyhydroxyalkanoates (PHA) and water-soluble polyvinyl alcohol (PVA) NP for their lung and liver toxicity in mice. Airborne PVC NP could cause nasal and lung microbial dysbiosis, lung and serum metabolic disruption, liver transcriptomic dysregulation, and result in lung and liver toxicity. In contrast, airborne PHA and PVA NP could induce nasal and lung microbial alterations, lung and serum metabolic disruption, liver transcriptomic disturbance, and lead to mild lung toxicity. As for foodborne PHA, PVA and PVC NP, they all could induce gut microbial dysbiosis, gut and serum metabolic disruption. Foodborne PVC NP could cause similar transcriptomic alterations and greater histological changes in liver compared to PHA NP, while foodborne PVA NP could induce transcriptomic disturbance but not apparent pathology in liver. Among the various alterations, multiple lung pathways (e.g., "renal cell carcinoma") and liver pathways (e.g., "arachidonic acid metabolism") were commonly greatly enriched by airborne PHA and PVA NP but not PVC NP, while multiple liver pathways (e.g., "pancreatic secretion") were commonly largely intensified by foodborne PVC and PHA NP but not PVA NP, aligning with the histological differences between groups. The relevant findings suggest PVA and PHA NP have lower lung and liver toxicity than PVC NP. The results could also benefit the clinical diagnoses of liver and lung toxicity induced by airborne and foodborne PVC, PVA and PHA NP. [ABSTRACT FROM AUTHOR]

Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant. Hence, evaluating the influence of different vehicles on the lung due to intratracheal instillation is crucial. We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor® P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicletreated groups but was minimal in the group administered saline, somewhat higher in the groups administered pure water, PBS, 0.1% Tween 20, and 1% BSA, and notably higher in the group administered 0.5% KP188. The results from BALF analysis indicated that intratracheal instillation of 0.5% KP188 also induced alveolar damage. Additionally, administering pure water did not appear to cause tissue damage. Eosinophil infiltration in the interstitial regions was histopathologically observed. Altogether, the results of this study are helpful for the selection of appropriate vehicles for use in intratracheal instillation studies. [ABSTRACT FROM AUTHOR]

Engineered nanoparticles (NPs) have been increasingly used in numerous fields over the last decade. In particular, iron oxide NPs (Fe2O3NPs) and silver NPs (AgNPs) have contributed to the current increase in NP usage. However, the possible side effects of increased NP exposure remain not fully elucidated. The present study aimed to assess the toxic effects of Fe2O3NPs and AgNPs, both individually and in combination, on the heart and lungs of male rats. To evaluate the in vivo NP toxic effects, the experimental animals were orally administered with Fe2O3NPs (5 mg/kg) and/or AgNPs (50 mg/kg). Animals were treated every day for 79 days. The results demonstrated that at the molecular level, Fe2O3NPs and AgNPs caused marked DNA base oxidation as indicated by the elevated DNA content of 8-hydroxy-2−deoxyguanosine in the heart and lungs. Fe2O3NPs and/or AgNPs decreased paraoxonase 1, antioxidant enzymes, total antioxidant capacity, and reduced glutathione in heart and lung. A dose-dependent increase in production of creatine kinase, thiobarbituric acid-reactive substances, nitric oxide end products, tumor necrosis factor-α, interleukin-6 and lipid profiles was detected. Histological changes were also evident in heart and lung tissues. The two NPs demonstrated similar toxic effects for the majority of factors when co-supplemented. In conclusion, the present study identified that Fe2O3NPs and AgNPs, alone and in combination, induced cardiotoxicity and lung toxicity. Furthermore, findings demonstrated that there was a greater toxic effect due to administration of both NPs compared to individual administration. It was hypothesized that the toxic effects may be mediated through the induction of oxidative DNA damage, lipid peroxidation, shifting redox status, disrupted gene expression, and deregulation in cytokine production. [ABSTRACT FROM AUTHOR]

Many constituents of tobacco smoke (TS) require bioactivation to exert toxic effects; however, few studies have examined the role of bioactivation enzymes in the adverse effects of TS exposure. This knowledge gap is a major source of uncertainty for risk assessment and chemoprevention efforts. Our aim is to test the hypothesis that cytochrome P450 (P450) enzyme-mediated bioactivation is essential to the development of TS exposure-induced lung toxicity, by determining the contributions of P450 enzymes in the mouse Cyp2abfgs gene subfamilies to environmental tobacco smoke (ETS)-induced lung inflammation. Adult female wildtype (WT) and Cyp2abfgs -null mice (both on C57BL/6J background) were exposed to filtered air or ETS, intermittently, for 1 or 2 weeks. Lung inflammation was assessed by quantification of inflammatory cells, cytokines, chemokines, and proteins in bronchoalveolar lavage fluid (BALF) and histopathological analysis. Glutathione (GSH) conjugates of 2 ETS constituents, naphthalene (NA), and 3-methylindole (3MI), were measured in mice exposed to ETS for 4 h. Persistent macrophagic and neutrophilic lung inflammation was observed in ETS-exposed WT mice; the extent of which was significantly reduced in ETS-exposed Cyp2abfgs -null mice. Levels of proinflammatory cytokines and chemokines, along with the total protein concentration, were increased in cell-free BALF from ETS-exposed WT mice, but not Cyp2abfgs -null mice. Additionally, GSH conjugates of NA and 3MI were detected in the lungs of WT, but not Cyp2abfgs -null, mice following ETS exposure. These results provide the first in vivo evidence that the mouse Cyp2abfgs gene cluster plays an important role in ETS-induced lung inflammation. [ABSTRACT FROM AUTHOR]

Furan, a possible human carcinogen, is a product of incomplete combustion and is present in cigarette smoke, engine exhaust, and processed food. Oral administration induces liver toxicity and carcinogenesis in F344 rats and B6C3F1 mice. To assess possible adverse effects from inhalation, A/J mice were nose-only exposed for 3 hours to furan (0, 30, 75, 150, 300, or 600 ppmv) and euthanized after 24 hours, 48 hours, or 1 week. Histopathology evaluation revealed bronchiolar club cell necrosis (diffuse, marked) with airway denudation following exposure to 300 and 600 ppmv furan with evidence of club cell regeneration and partial repair after 1 week. Initial signs of hepatotoxicity were observed in the 150 ppmv furan-exposed group. Acute necrosis and mineralization were observed in livers at 24 and 48 hours with hepatocyte regeneration by 1-week postexposure in mice exposed to 300 and 600 ppmv furan; the 300 ppmv exposed group had multifocal mineralization that evoked a mild granulomatous response. Measurement of urinary furan metabolites confirmed that the mice metabolized furan to the toxic intermediate, cis -2-butene-1,4-dial. These observations indicate that inhaled furan is toxic to lungs with club cells as the target as well as liver. [ABSTRACT FROM AUTHOR]

The characteristics of wildland fire smoke exposures which initiate or exacerbate cardiopulmonary conditions are unclear. We previously reported that, on a mass basis, lung toxicity associated with particulate matter (PM) from flaming smoke aspirated into mouse lungs is greater than smoldering PM. In this study, we developed a computer-controlled inhalation system which can precisely control complex biomass smoke emissions from different combustion conditions. This system was used to examine the toxicity of inhaled biomass smoke from peat, eucalyptus, and oak fuels generated under smoldering and flaming phases with emissions set to the same approximate concentration of carbon monoxide (CO) for each exposure (60–110 ppm), resulting in PM levels of ~ 4 mg/m3 for flaming and ~ 40 mg/m3 for smoldering conditions. Mice were exposed by inhalation 1 h/day for 2 days, and assessed for lung toxicity at 4 and 24 h after the final exposure. Peat (flaming and smoldering) and eucalyptus (smoldering) smoke elicited significant inflammation (neutrophil influx) in mouse lungs at 4 h with the peat (flaming) smoke causing even greater lung inflammation at 24-h post-exposure. A significant alteration in ventilatory timing was also observed in mice exposed to the peat (flaming) and eucalyptus (flaming and smoldering) smoke immediately after each day of exposure. No responses were seen for exposures to similar concentrations of flaming or smoldering oak smoke. The lung toxicity potencies (neutrophil influx per PM mass) agreed well between the inhalation and previously reported aspiration studies, demonstrating that although flaming smoke contains much less PM mass than smoldering smoke, it is more toxic on a mass basis than smoldering smoke exposure, and that fuel type is also a controlling factor. [ABSTRACT FROM AUTHOR]

[Display omitted] • Foodborne polyethersulfone micro/nanoplastics affected gut microbiota-gut-liver axis. • Airborne polyethersulfone micro/nanoplastics disrupted airway microbiota-lung axis. • Foodborne polyethersulfone nanoplastics induced greater liver toxicity. • Airborne polyethersulfone nanoplastics induced greater lung toxicity. Micro/nanoplastics (MNP) are ubiquitous in the environment and multiple living organisms. The toxicity of some common types of MNP, e.g., polyethersulfone (PES) MNP, remains poorly understood. Multi-omics approaches were used in this study to determine the effects of foodborne and airborne PES MNP on liver and lung, respectively. Foodborne MNP were capable of inducing gut microbial dysbiosis, gut and serum metabolic disruption, and liver transcriptomic dysregulation, and affecting serum antioxidant activity and liver function, resulting in liver injury. As for the airborne MNP, they were found to induce nasal and lung microbial dysbiosis, serum and lung metabolic disruption, and liver transcriptome disturbance, and cause disrupted serum antioxidant activity and lung injury. Foodborne and airborne PES NP were found to respectively induce greater liver and lung toxicity than MP, which could be associated with the differences between NP and MP exposures. The relevant results suggest that foodborne PES MNP could disrupt the "gut microbiota-gut-liver" axis and induce hepatic injury, while airborne PES MNP could affect the "airborne microbiota-lung" axis and cause lung injury. The findings could benefit the diagnoses of liver and lung injury respectively induced by foodborne and airborne PES MNP, as well as the proper use of PES in human living environment. [ABSTRACT FROM AUTHOR]