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Frontiers in Public Health 2023The study aimed to determine whether the National Cancer Institute's (NCI) recent suggestion of associations between acrylonitrile (AN) exposure and mortality in lung...
OBJECTIVES
The study aimed to determine whether the National Cancer Institute's (NCI) recent suggestion of associations between acrylonitrile (AN) exposure and mortality in lung and bladder cancer and pneumonitis is robust to alternative methods of data analysis.
MATERIALS AND METHODS
We used the Richardson method to indirectly adjust risk ratios (RRs) in relation to AN exposure for potential confounding by smoking and asbestos. We repeated key analyses omitting workers from Plant 4 to account for possible local, historical shipyard-related asbestos exposures.
RESULTS
The adjustment of lung cancer RRs for confounding by both smoking and asbestos and omitting Plant 4 workers yielded mostly decreased RRs and much less evidence of a positive association with cumulative AN exposure.
CONCLUSION
Overall, our reanalysis provided little evidence to support NCI's suggestion of associations between AN exposure and mortality in lung and bladder cancer and pneumonitis.
Topics: United States; Humans; Cohort Studies; Acrylonitrile; National Institute for Occupational Safety and Health, U.S.; Occupational Exposure; Lung Neoplasms; Asbestos; Urinary Bladder Neoplasms
PubMed: 37089484
DOI: 10.3389/fpubh.2023.1122346 -
JCI Insight Aug 2021Gorham-Stout disease (GSD) is a sporadically occurring lymphatic disorder. Patients with GSD develop ectopic lymphatics in bone, gradually lose bone, and can have...
Gorham-Stout disease (GSD) is a sporadically occurring lymphatic disorder. Patients with GSD develop ectopic lymphatics in bone, gradually lose bone, and can have life-threatening complications, such as chylothorax. The etiology of GSD is poorly understood, and current treatments for this disease are inadequate for most patients. To explore the pathogenesis of GSD, we performed targeted high-throughput sequencing with samples from a patient with GSD and identified an activating somatic mutation in KRAS (p.G12V). To characterize the effect of hyperactive KRAS signaling on lymphatic development, we expressed an active form of KRAS (p.G12D) in murine lymphatics (iLECKras mice). We found that iLECKras mice developed lymphatics in bone, which is a hallmark of GSD. We also found that lymphatic valve development and maintenance was altered in iLECKras mice. Because most iLECKras mice developed chylothorax and died before they had significant bone disease, we analyzed the effect of trametinib (an FDA-approved MEK1/2 inhibitor) on lymphatic valve regression in iLECKras mice. Notably, we found that trametinib suppressed this phenotype in iLECKras mice. Together, our results demonstrate that somatic activating mutations in KRAS can be associated with GSD and reveal that hyperactive KRAS signaling stimulates the formation of lymphatics in bone and impairs the development of lymphatic valves. These findings provide insight into the pathogenesis of GSD and suggest that trametinib could be an effective treatment for GSD.
Topics: Acrylonitrile; Aniline Compounds; Animals; Bone and Bones; Disease Models, Animal; Gain of Function Mutation; High-Throughput Nucleotide Sequencing; Humans; Lymphangiogenesis; Lymphatic Vessels; Mice; Osteolysis, Essential; Proto-Oncogene Proteins p21(ras); Pyridones; Pyrimidinones; Signal Transduction; Tertiary Lymphoid Structures
PubMed: 34156985
DOI: 10.1172/jci.insight.149831 -
Materials (Basel, Switzerland) Jun 2024The glycolysis process of flexible polyurethane foams containing styrene-acrylonitrile and calcium carbonate as fillers was explored in detail. The use of DABCO as a...
The glycolysis process of flexible polyurethane foams containing styrene-acrylonitrile and calcium carbonate as fillers was explored in detail. The use of DABCO as a catalyst allowed us to reduce the catalyst concentration and the polyurethane-to-glycol mass ratio to 0.1% and 1:1, respectively. The glycolysis process allowed us to obtain a high-purity polyol (99%), which can totally replace raw polyols in the synthesis of new flexible polyurethane foams, maintaining the standard mechanical properties of the original one and modifying the ratio of isocyanates employed to correct the closed cell structure caused by the impurities present in the recovered polyol. This isocyanate mixture was also optimized, resulting in a ratio of 30 and 70% of the isocyanates TDI80 and TDI65, respectively. Additionally, the fillers incorporated in the glycolyzed foams were recovered. Both recovered fillers, styrene-acrylonitrile and calcium carbonate, were fully characterized, showing a quality very similar to that of commercial compounds. Finally, the replacement of commercial fillers by the recovered ones in the synthesis of new polyurethane foams was studied, demonstrating the feasibility of using them in the synthesis of new foams without significantly altering their properties.
PubMed: 38930213
DOI: 10.3390/ma17122844 -
Nanomaterials (Basel, Switzerland) Jun 2020Thermally stabilized and subsequently carbonized nanofibers are a promising material for many technical applications in fields such as tissue engineering or energy...
Thermally stabilized and subsequently carbonized nanofibers are a promising material for many technical applications in fields such as tissue engineering or energy storage. They can be obtained from a variety of different polymer precursors via electrospinning. While some methods have been tested for post-carbonization doping of nanofibers with the desired ingredients, very little is known about carbonization of blend nanofibers from two or more polymeric precursors. In this paper, we report on the preparation, thermal treatment and resulting properties of poly(acrylonitrile) (PAN)/poly(vinylidene fluoride) (PVDF) blend nanofibers produced by wire-based electrospinning of binary polymer solutions. Using a wide variety of spectroscopic, microscopic and thermal characterization methods, the chemical and morphological transition during oxidative stabilization (280 °C) and incipient carbonization (500 °C) was thoroughly investigated. Both PAN and PVDF precursor polymers were detected and analyzed qualitatively and quantitatively during all stages of thermal treatment. Compared to pure PAN nanofibers, the blend nanofibers showed increased fiber diameters, strong reduction of undesired morphological changes during oxidative stabilization and increased conductivity after carbonization.
PubMed: 32575861
DOI: 10.3390/nano10061210 -
International Journal of Molecular... Jan 2023New -alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles with putative kinase inhibitory activity and their (-cymene)Ru(II) piano-stool complexes were prepared and...
New -alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles with putative kinase inhibitory activity and their (-cymene)Ru(II) piano-stool complexes were prepared and tested for their antiproliferative efficacy in various cancer models. Some of the indole-based derivatives inhibited tumor cell proliferation at (sub-)micromolar concentrations with IC values below those of the clinically relevant multikinase inhibitors gefitinib and sorafenib, which served as positive controls. A focus was set on the investigation of drug mechanisms in HCT-116 p53-knockout colon cancer cells in order to evaluate the dependence of the test compounds on p53. Colony formation assays as well as experiments with tumor spheroids confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic caspase-3/7 activity and ROS formation, as well as anti-angiogenic properties. Docking calculations with EGFR and VEGFR-2 identified the two 3-aryl-2-(pyrid-3-yl)acrylonitrile derivatives and as potential kinase inhibitors with a preferential activity against the VEGFR-2 tyrosine kinase. Forthcoming studies will further unveil the underlying mode of action of the promising new derivatives as well as their suitability as an urgently needed novel approach in cancer treatment.
Topics: Humans; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Indoles; Molecular Docking Simulation; Molecular Structure; Protein Kinase Inhibitors; Structure-Activity Relationship; Tumor Suppressor Protein p53; Tyrphostins; Vascular Endothelial Growth Factor Receptor-2; HCT116 Cells
PubMed: 36614289
DOI: 10.3390/ijms24010854 -
SN Applied Sciences Dec 2022Fused filament fabrication is a 3D printing technique that has gained widespread use from homes to schools to workplaces. Thermoplastic filaments, such as...
Fused filament fabrication is a 3D printing technique that has gained widespread use from homes to schools to workplaces. Thermoplastic filaments, such as acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA), are extruded at temperatures near their respective glass transition temperature or melting point, respectively. Little has been reported on the inorganic elemental composition and concentrations present in these materials or the methods available for extracting that information. Because inorganic constituents may be included in the aerosolized particulates emitted during the printing process, identifying elements that could be present and at what specific concentrations is critical. The objective of the current research is to determine the range of metals present in thermoplastic filaments along with their relative abundance and chemical speciation as a function of polymer type, manufacturer, and color. A variety of filaments from select manufacturers were digested using a range of techniques to determine the optimal conditions for metal extraction from ABS and PLA polymers. The extraction potential for each method was quantified using by ICP-MS analysis. When possible, further characterization of the chemical composition of the filaments was investigated using X-ray Absorption spectroscopy to determine chemical speciation of the metal. Optimal digestion conditions were established using a high temperature, high pressure microwave-assisted acid digestion method to produce the most complete and repeatable extraction results. The composition and abundance of metals in the filaments varied greatly as a function of polymer, manufacturer, and color. Potential elements of concern present in the filaments at elevated concentration included that could pose a respiratory risk included Si, Al, Ti, Cu, Zn, and Sn. XAS analysis revealed a mixture of metal oxides, mineral, and organometallic compounds were present in the filaments that were being used to increase opaqueness impart color (dyes), polymeric catalysts, and flame retardants. This work shows that a variety of metals are present in the starting materials used for 3D printing and depending on their partitioning into 3D printed products and byproducts as well as the exposure route, may pose a health risk which merits further investigation.
PubMed: 37383926
DOI: 10.1007/s42452-022-05221-7 -
Bioorganic Chemistry Jul 2022Leishmaniasis produces approximately-one million of new cases annually, making it one of the most important tropical diseases. As current treatments are not fully...
Leishmaniasis produces approximately-one million of new cases annually, making it one of the most important tropical diseases. As current treatments are not fully effective and are toxic, it is necessary to develop new therapies that are more effective and less toxic, and cause a controlled cell death, with which we can avoid the immunological problems caused by necrosis. In this work 32 acrylonitriles were studied in vitro against Leishmania amazonensis. Three compounds Q20 (12.41), Q29 (11.2) and Q31 (11.56) had better selectivity than the reference compound, miltefosine (11.14) against promastigotes of these parasites, for this reason they were selected to determine their mechanism of action to know the cell death type of they produce. The results of the mechanisms of action show that these three acrylonitriles tested produce chromatin condensation, decreased mitochondrial membrane potential, altered plasma permeability and production of reactive oxygen species. All these characteristic events seem to indicate programmed cell death. Therefore, this study demonstrates the activity of acrylonitriles derivatives as possible leishmanicidal agents.
Topics: Acrylonitrile; Animals; Antiprotozoal Agents; Cell Death; Leishmania mexicana; Macrophages; Mice; Mice, Inbred BALB C
PubMed: 35597192
DOI: 10.1016/j.bioorg.2022.105872 -
ACS Chemical Biology Oct 2022Nanopore direct RNA sequencing (dRNA-Seq) reads reveal RNA modifications through consistent error profiles specific to a modified nucleobase. However, a null data set is...
Nanopore direct RNA sequencing (dRNA-Seq) reads reveal RNA modifications through consistent error profiles specific to a modified nucleobase. However, a null data set is required to identify actual RNA modification-associated errors for distinguishing it from confounding highly intrinsic sequencing errors. Here, we reveal that inosine creates a signature mismatch error in dRNA-Seq reads and obviates the need for a null data set by harnessing the selective reactivity of acrylonitrile for validating the presence of actual inosine modifications. Selective reactivity of acrylonitrile toward inosine altered multiple dRNA-Seq parameters like signal intensity and trace value. We also deduced the stoichiometry of inosine modification through deviation in signal intensity and trace value using this chemical biology approach. Furthermore, we devised Nano ICE-Seq, a protocol to overcome the low coverage issue associated with direct RNA sequencing. Taken together, our chemical probe-based approach may facilitate the knockout-free detection of disease-associated RNA modifications in clinical scenarios.
Topics: Nanopore Sequencing; High-Throughput Nucleotide Sequencing; Acrylonitrile; Inosine; RNA
PubMed: 36190780
DOI: 10.1021/acschembio.2c00221 -
Polymers Nov 2021The miscibility and phase separation of poly(methyl methacrylate) (PMMA) and styrene-acrylonitrile (SAN) have already been investigated using various methods. However,...
The miscibility and phase separation of poly(methyl methacrylate) (PMMA) and styrene-acrylonitrile (SAN) have already been investigated using various methods. However, these methods have limitations that often result in inconsistent characterization. Consequently, the reasons for the dependence of miscibility on composition as well as on processing temperature have not yet been proved. The phase separation of PMMA/SAN blends was therefore investigated for the first time using a novel technique, nanoscale AFM-IR. It couples nanoscale atomic force microscopy (AFM) with infrared (IR) spectroscopy. Therefore, the phase morphology can be chemically identified and precisely classified within the nm-regime. The PMMA/SAN blends, on the other hand, were analyzed of their changes in morphology under different thermal treatments. It was possible to visualize and define the phase separation, as well as dependence of the miscibility on the mixing ratio. In the miscible domain, no two individual phases could be detected down to the nanometer range. It was shown that with increasing temperature, the morphology changes and two different phases are formed, where the phase boundaries can be sharply defined. The onset of these changes could be identified at temperatures of about 100 °C.
PubMed: 34771366
DOI: 10.3390/polym13213809 -
Materials (Basel, Switzerland) Oct 2020There is a pressing demand to synthesize polymers that have antibacterial and antifungal properties. The aim of this study was to synthesize a crosslinked hydrophilic...
There is a pressing demand to synthesize polymers that have antibacterial and antifungal properties. The aim of this study was to synthesize a crosslinked hydrophilic terpolymer with acrylamide, acrylonitrile, acrylic acid, acrylamido-2-methylpropane sulphonic acid and ethylene glycol dimethacrylate as a crosslinker. The chemical structure and thermal stability of the prepared cross-linked terpolymers were confirmed by spectroscopic and thermal analyses. Moreover, the swelling experiments were performed to investigate their swelling capacity. Furthermore, the efficiency of the synthesized cross-linked polymer gels was assessed as an antimicrobial agent against Gram-positive, Gram-negative bacteria and fungal strains. The synthesized polymers showed broad inhibition effect, with more antibacterial activity by the AM4 polymer sample containing high percentage of acrylonitrile monomer in the prepared terpolymers (4 mol ratio of acrylic acid: 1 mol ratio of acrylamide: 16 mole ratio of acrylonitrile against Gram negative bacterial strain), while sample M3 terpolymer (1 mol ratio of acrylamide: 1 mole ratio acrylonitrile: 3 mole ratio of acrylamido-2-methylpropane sulphonic acid) showed a promising anti-fungal activity.
PubMed: 33143385
DOI: 10.3390/ma13214891