This study investigated the potential pulmonary toxicity of polycarbonate (PC) emissions from fused filament fabrication (FFF) three-dimensional printing (3DP) via inhalation in Sprague Dawley rats. Previously, our results demonstrated no significant pulmonary effects following exposure to a 0.5 mg/m PC. A new exposure apparatus was developed that exposed animals at a concentration of 2.5 mg/m. Sixty rats were randomized into control (filtered air) and exposure groups ( = 30/group). Each group was further divided into five subgroups ( = 6/subgroup) with exposure durations of 1, 4, 8, 15, or 30 days (4 hr/day, 4 days/week). Following a 24-hr post-exposure period, body weight was measured, and blood samples were collected for hematological and biochemical analysis. Bronchoalveolar lavage fluid (BALF) was obtained from the right lung for cytology. The left lung and head/nasal tissues were preserved for histopathological evaluation. Lung deposition was estimated using the Multiple-Path Particle Dosimetry model, electron microscopy, and enhanced darkfield microscopy. In addition, filter samples were collected to measure bisphenol A. Exposure resulted in an estimated deposition of 0.28 µg/day within the alveoli and small airways. Microscopy indicated limited evidence of macrophage uptake. No significant changes were observed in BALF cell counts, lactate dehydrogenase activity, or hematological parameters. BALF levels of tissue inhibitor of metalloproteinases-1 and protein were elevated in the 30-day exposure group, although histopathology revealed no exposure-related changes in the lungs. In conclusion, this study found no marked pulmonary inflammation or toxicity in rats exposed to 2.5 mg/m of PC 3D printing emissions for up to 30 days (4 hr/day).
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http://dx.doi.org/10.1080/15287394.2025.2473559 | DOI Listing |
Sci Transl Med
March 2025
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2025
Laboratorio 1. Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas-Universidad de Salamanca and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Salamanca 37007, Spain.
We evaluated the in vivo therapeutic efficacy and tolerability of BI-3406-mediated pharmacological inhibition of SOS1 in comparison to genetic ablation of this universal Ras-GEF in various KRAS-dependent experimental tumor settings. Contrary to the rapid lethality caused by SOS1 genetic ablation in SOS2 mice, SOS1 pharmacological inhibition by its specific inhibitor BI-3406 did not significantly affect animal weight/viability nor cause noteworthy systemic toxicity. Allograft assays using different KRAS cell lines showed that treatment with BI-3406 impaired RAS activation and RAS downstream signaling and decreased tumor burden and disease progression as a result of both tumor-intrinsic and -extrinsic therapeutic effects of the drug.
View Article and Find Full Text PDFAnn Surg Oncol
March 2025
Department of Cardiothoracic Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA.
Background: Treatment of non-small cell lung cancer (NSCLC) remains challenging; 5-year survival is as low as 24% for resectable disease. However, the outlook for stage IA NSCLC is favorable, with 5-year survival exceeding 74% and with surgery often being curative. Despite this positive prognosis, low socioeconomic status has been shown to correlate with nonstandard treatment and worse overall survival specifically in stage IA.
View Article and Find Full Text PDFMed Oncol
March 2025
Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, 281406, India.
Cancer continues to be a significant global health concern, consistently ranking as one of the leading causes of mortality across diverse populations and socio-economic contexts. Genistein, a soy-derived isoflavonoid, has gained significant attention for its diverse health benefits, particularly its potent anticancer activity. Emerging pre-clinical and clinical evidences highlights its ability to modulate key cellular processes, including apoptosis, autophagy, angiogenesis, metastasis, immune responses and cell cycle regulation.
View Article and Find Full Text PDFPurinergic Signal
March 2025
Division of Cardiology, Department of Medicine Solna, Karolinska Institutet, Solna, Stockholm, 17177, Sweden.
Atherosclerosis, a chronic inflammatory disease driven by lipid deposition and immune cell activation, remains a leading cause of cardiovascular morbidity and mortality. Emerging evidence highlights the role of purinergic signalling in atherogenesis, particularly the P2Y receptor in macrophages [1]. Using RNA sequencing, proteomics, expression and functional validation in cells, mouse models and human materials, this study provides comprehensive mechanistic insights into how macrophage P2Y receptors contribute to foam cell formation and plaque development through the phospholipase Cβ (PLCβ)/store-operated Ca entry/calreticulin/scavenger receptor A (SR-A) pathway.
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