The beneficial outcome associated with the use of proton pump inhibitors (PPIs) in idiopathic pulmonary fibrosis (IPF) has been reported retrospective studies. To date, no prospective study conducted to confirm these outcomes. In addition, potential mechanism by which PPIs improve measures lung function and/or transplant-free survival IPF not elucidated.Here, we used biochemical, cell biological and preclinical studies evaluate regulation markers inflammation fibrosis. our vitro studies,...

Conventional in vitro exposure methods for cultured human lung cells rely on prior suspension of particles a liquid medium; these have limitations intensity and may modify the particle composition. Here electrostatic precipitation was used as an effective method such exposures. An obsolete aerosol sampler modified to provide viable environment within deposition field grown membranous support. Particle particle-induced toxicological effects variety including standardized polystyrene latex...

The presence of endogenous and exogenous N(2)-hydroxymethyl-dG adducts in DNA from the nasal mucosa bone marrow cynomolgus macaques exposed to 1.9 6.1 ppm [(13)CD(2)]-formaldehyde for 6 h a day 2 consecutive days was investigated using highly sensitive nano-UPLC-MS/MS method with limit detection 20 amol. Both were readily detected quantified tissues both exposure groups, an dependent increase observed. In contrast, only detectable marrow, even though ∼10 times more analyzed.

Formaldehyde is not only a widely used chemical with well-known carcinogenicity but also normal metabolite of living cells. It thus poses unique challenges for understanding risks associated exposure. N2-hydroxymethyl-dG (N2-HOMe-dG) the main formaldehyde-induced DNA mono-adduct, which together DNA-protein crosslinks (DPCs) and toxicity-induced cell proliferation, play important roles in mutagenic mode action cancer. In this study, N2-HOMe-dG was shown to be an excellent biomarker direct...

Radiation-induced pulmonary fibrosis is a severe complication of patients treated with thoracic irradiation. We have previously shown that syndecan-2 reduces by exerting alveolar epithelial cytoprotective effects. Here, we investigate whether attenuates radiation-induced inhibiting fibroblast activation. C57BL/6 wild-type mice and transgenic overexpress human in macrophages were exposed to 14 Gy whole-thoracic radiation. At 24 weeks after irradiation, lungs collected for histological,...

In this study, both endogenous and exogenous N2-hydroxymethyl-dG adducts in nasal DNA of rats exposed to 0.7, 2, 5.8, 9.1, or 15.2 ppm [13CD2] formaldehyde for 6 h were quantified by a highly sensitive nano-UPLC-MS/MS method. Our data clearly demonstrated that form nonlinear fashion, with 21.7-fold increase exposure causing 286-fold adducts. The ratio exogenous/endogenous dominated at low exposures, comprising more than 99%. contrast, not detectable the bone marrow formaldehyde.

MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses formaldehyde, a air pollutant and known carcinogen that disrupts expression profiles. Rats were exposed by inhalation either 0 or 2 ppm formaldehyde for 7, 28, 28 days followed 7-day recovery. Genome-wide profiles assessed within the nasal...

BackgroundEmerging evidence suggests that the systemic vasculature may be a target of inhaled pollutants vehicular origin. We have identified several murine markers vascular toxicity appear sensitive to inhalation exposures combustion emissions.ObjectiveWe sought examine relative impact various pollutant atmospheres and specific individual components on these altered transcription lipid peroxidation.MethodsApolipoprotein E knockout (ApoE−/−) mice were exposed whole emissions (gasoline,...

Cesium-137 is a fission product of uranium and plutonium in nuclear reactors released large quantities during explosions or detonation an improvised device containing this isotope. This environmentally persistent radionuclide undergoes radioactive decay with the emission beta particles as well gamma radiation. Exposure to 137Cs at high doses can cause acute radiation sickness increase risk for cancer death. The serious health risks associated exposure makes it critical understand how affects...

Cesium-137 is a radionuclide of concern in fallout from reactor accidents or nuclear detonations. When ingested inhaled, it can expose the entire body for an extended period time, potentially contributing to serious health consequences ranging acute radiation syndrome increased cancer risks. To identify changes gene expression that may be informative detecting such exposure, and begin examining molecular responses involved, we have profiled global blood male C57BL/6 mice injected with...

Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it imperative to understand the mechanisms underlying formaldehyde-induced toxicity carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied relation formaldehyde. Our previous investigation demonstrated that formaldehyde exposure human lung cells disruptions miRNA expression profiles vitro.Using vivo model, we set...

In this study ultra performance liquid chromatography (UPLC) coupled to time-of-flight mass spectrometry in the MS(E) mode was used for rapid and comprehensive analysis of metabolites serum mice exposed internal exposure by Cesium-137 ((137)Cs). The effects (137)Cs were studied at several time points after injection (137)CsCl mice. Over 1800 spectral features detected positive negative electrospray ionization modes combined. Detailed statistical revealed that associated with amino acid...

An irradiation chamber designed for reproducible generation of inhalation test atmospheres secondary organic aerosol (SOA) was used to evaluate cardiopulmonary responses in rodents exposed SOA derived from the oxidation α-pinene. were produced with 10:1 ratios α-pinene:nitrogen oxides (NOx) and 10:1:1 oxides:sulfur dioxide (SO2). yield 200 μg m−3 particulate matter (PM). Exposures conducted downstream honeycomb denuders employed remove gas-phase precursors reaction products. Nose-only...

Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers human COPD. These include a anatomy that differs from humans, the limited airway pathologies lymphoid aggregates develop in smoke-exposed mice, challenges associated with serial biological sampling. Thus, we assessed utility cigarette smoke (CS)-exposed cynomolgus macaque as nonhuman primate (NHP) large model Twenty-eight NHPs were exposed to air...

Objective: The use of noncultured autologous stromal vascular fraction or clinical grade adipose-derived regenerative cells (ADRCs) is a promising strategy to promote wound healing and tissue repair. Nevertheless, issues regarding the optimal mode administration remain unclear. purpose this study was compare effects local injection topical spray delivery ADRCs in porcine model thermal burns. Approach: Full-thickness burns were created on dorsum 10 Gottingen minipigs. Two days following...

The radioactive isotope Strontium-90 (90Sr) may be released as a component of fallout from nuclear accidents, or in the event radiological incident such detonation an improvised device, and if ingested poses significant health risk to exposed individuals. In order better understand response 90Sr, using easily attainable standard biodosimetry sample fluid, we analyzed global transcriptomic blood cells vivo model system. We injected C57BL/6 mice with solution 90SrCl2 followed them over 30-day...

With formaldehyde as the major source of endogenous N⁶-formyllysine protein adducts, we quantified and exogenous in nasal epithelium rats exposed by inhalation to 0.7, 2, 5.8, 9.1 ppm [¹³C²H₂]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous was detected epithelium, with concentration-dependent formation total well fractionated (cytoplasmic, membrane, nuclear) proteins, but not lung, liver, or bone marrow. Endogenous adducts dominated at all exposure...

Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern the possible release degradation products into atmosphere, warranting evaluation potential pulmonary effects inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), piperazine (PIP) underwent oxidative CO2-mediated for 75 days. C57bl/6N mice were exposed 7 days by inhalation 25 ppm neat or equivalant concentration in degraded...

Despite considerable research into the environmental risks and biological effects of exposure to external beam γ rays, incorporation radionuclides has largely been understudied. This dosimetry risk assessment is challenging for first responders in field during a nuclear or radiological event. Therefore, we have developed workflow assessing injury responses easily obtainable biofluids, such as urine serum, result internal emitters cesium-137 ((137)Cs) strontium-90 ((90)Sr) mice. Here report...

The adverse health effects of environmental exposure to gaseous and particulate components vehicular emissions are a major concern among urban populations. A link has been established between respiratory the development cardiovascular disease (CVD), but mechanisms driving this interaction remain unknown. Chronic inhalation mixed vehicle linked CVD in animal models. This study evaluated temporal acute (MVE; gasoline diesel emissions) on potentially active metabolites serum exposed mice....

Pulmonary nontuberculous mycobacteria (NTM) infection is recognized as a major global health concern due to its rising prevalence worldwide. As an opportunistic pathogen with increasing antibiotics resistance, prolonged systemic dosing multiple remains the primary treatment paradigm. These treatments, administered predominantly by oral or parenteral routes, often lead toxicity. A novel inhaled formulation of clofazimine may finally resolve issues toxicity, thereby providing for improved NTM...

Internal emitters such as Strontium-90 (90Sr) pose a substantial health risk during and immediately after nuclear disaster or detonation of an improvised device. The environmental persistency potency 90Sr calls for urgent development high-throughput tests to establish levels exposure help triage potentially exposed individuals who were in the immediate area disaster. In response these concerns, our team focused on developing robust metabolomic profile urine using mouse model. sensitivity...

To develop an approach that models the cutaneous healing occurs in a patient with full thickness thermal burn injury complicated by total body radiation exposure sufficient to induce sub-lethal prodromal symptoms. An assessment of effects autologous cell therapy on wound concomitant was used validate utility model.Göttingen minipigs were subjected 1.2 Gy irradiation 6 MV X-ray linear accelerator followed ∼10 cm2 burns (pre-heated brass block calibrated spring). Three days after injury,...

Tire and road wear particles (TRWP) are a component of ambient particulate matter (PM) produced from the interaction tires with roadway. Inhalation PM has been associated cardiopulmonary morbidities mortalities thought to stem pulmonary inflammation. To determine whether TRWP may contribute these events, effects subacute inhalation were evaluated in rats. collected at simulator laboratory, aerosolized, used expose male female Sprague-Dawley rats (n = 10/treatment group) ~10, 40, or 100 μg/m3...

To investigate the toxicological effects of biogenic- versus anthropogenic-source secondary organic aerosol (SOA) on cardiovascular system, Secondary Particulate Health Effects Research program irradiation chamber was used to expose atherosclerotic apolipoprotein E null (Apo E−/−) mice SOA from oxidation either α-pinene or toluene for 7 days. atmospheres were produced yield 250–300 μg/m3 particulate matter and ratios 10:1:1 α-pinene:nitrogen oxide (NOx):ammonia (NH3); 10:1:1:1...