Particle size is generally considered to be the primary factor in the design of nanocrystal photocatalysts, because the reduction of particle size increases the number of active sites. However, the ...benefit from the size reduction can be canceled by a higher electron−hole recombination rate due to the confined space in sphere-shaped nanoparticles. Here we report a mechanistic study on a novel nanobelt structure that overcomes the drawback of sphere-shaped nanoparticles. Single-crystalline anatase TiO2 nanobelts with two dominant surfaces of (101) facet exhibit enhanced photocatalytic activity over the nanosphere counterparts with an identical crystal phase and similar specific surface area. The ab initio density functional theory (DFT) calculations show that the exposed (101) facet of the nanobelts yields an enhanced reactivity with molecular O2, facilitating the generation of superoxide radical. Moreover, the nanobelts exhibit a lower electron−hole recombination rate than the nanospheres due to the following three reasons: (i) greater charge mobility in the nanobelts, which is enabled along the longitudinal dimension of the crystals; (ii) fewer localized states near the band edges and in the bandgap due to fewer unpassivated surface states in the nanobelts; and (iii) enhanced charge separation due to trapping of photogenerated electrons by chemisorbed molecular O2 on the (101) facet. Our results suggest that the photocatalysis efficiency of nanocrystals can be significantly improved by tailoring the shape and the surface structure of nanocrystals, which provides a new concept for rational design and development of high-performance photocatalysts.
Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco ...cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.
Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does ...the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO), and ventilation dust particles activated nuclear factor kappa B (NFκB) within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1β, IL-6, TNFα, and IL-8) within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1β release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Both acellular and cellular systems found ROS generation in e-cig emissions.•E-cig features (brand, flavor) highly influence ROS formation.•Operational parameters (puffing and voltage) highly ...influence on ROS formation.•E-cig emission can contain comparable level of ROS compared to tobacco cigarette.•Influence of parameters should be considered in e-cig toxicological studies.
Electronic cigarettes (e-cigs) have fast increased in popularity but the physico-chemical properties and toxicity of the generated emission remain unclear. Reactive oxygen species (ROS) are likely present in e-cig emission and can play an important role in e-cig toxicity. However, e-cig ROS generation is poorly documented. Here, we generated e-cig exposures using a recently developed versatile exposure platform and performed systematic ROS characterization on e-cig emissions using complementary acellular and cellular techniques: 1) a novel acellular Trolox-based mass spectrometry method for total ROS and hydrogen peroxide (H2O2) detection, 2) electron spin resonance (ESR) for hydroxyl radical detection in an acellular and cellular systems and 3) in vitro ROS detection in small airway epithelial cells (SAEC) using the dihydroethidium (DHE) assay. Findings confirm ROS generation in cellular and acellular systems and is highly dependent on the e-cig brand, flavor, puffing pattern and voltage. Trolox method detected a total of 1.2–8.9nmol H2O2eq./puff; H2O2 accounted for 12–68% of total ROS. SAEC cells exposed to e-cig emissions generated up to eight times more ROS compared to control. The dependency of e-cig emission profile on e-cig features and operational parameters should be taken into consideration in toxicological studies.
Recent research indicates that cadmium (Cd) induces oxidative damage in cells; however, the mechanism of the oxidative stress induced by this metal is unclear. We investigated the effects of Cd on ...the individual complexes of the electron transfer chain (ETC) and on the stimulation of reactive oxygen species (ROS) production in mitochondria. The activity of complexes II (succinate:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome
c oxidoreductase) of mitochondrial ETC from liver, brain, and heart showed greater inhibition by Cd than the other complexes. Cd stimulated ROS production in the mitochondria of all three tissues mentioned above. The effect of various electron donors (NADH, succinate, and 2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinol) on ROS production was tested separately in the presence and in the absence of Cd. ESR showed that complex III might be the only site of ROS production induced by Cd. The results of kinetic studies and electron turnover experiments suggest that Cd may bind between semiubiquinone and cytochrome
b
566 of the Q
0 site of cytochrome
b of complex III, resulting in accumulation of semiubiquinones at the Q
0 site. The semiubiquinones, being unstable, are prone to transfer one electron to molecular oxygen to form superoxide, providing a possible mechanism for Cd-induced generation of ROS in mitochondria.
Background: Engineered nanosized materials, such as single-wall carbon nanotubes (SWCNT), are emerging as technologically important in different industries. Objective: The unique physical ...characteristics and the pulmonary toxicity of SWCNTs raised concerns that respiratory exposure to these materials may be associated with cardiovascular adverse effects. Methods: In these studies we evaluated aortic mitochondrial alterations by oxidative stress assays, including quantitative polymerase chain reaction of mitochondrial (mt) DNA and plaque formation by morphometric analysis in mice exposed to SWCNTs. Results: A single intrapharyngeal instillation of SWCNTs induced activation of heme oxygenase-1 (HO-1), a marker of oxidative insults, in lung, aorta, and heart tissue in HO-1 reporter transgenic mice. Furthermore, we found that C57BL/6 mice, exposed to SWCNT (10 and$40\mu g/mouse$), developed aortic mtDNA damage at 7, 28, and 60 days after exposure. mtDNA damage was accompanied by changes in aortic mitochondrial glutathione and protein carbonyl levels. Because these modifications have been related to cardiovascular diseases, we evaluated whether repeated exposure to SWCNTs ($20\mu g/mouse$once every other week for 8 weeks) stimulates the progression of atherosclerosis in ApoE-/-transgenic mice. Although SWCNT exposure did not modify the lipid profiles of these mice, it resulted in accelerated plaque formation in$ApoE^{-/-} mice$fed an atherogenic diet. Plaque areas in the aortas, measured by the en face method, and in the brachiocephalic arteries, measured histopathologically, were significantly increased in the SWCNT-treated mice. This response was accompanied by increased mtDNA damage but not inflammation. Conclusions: Taken together, the findings are of sufficient significance to warrant further studies to evaluate the systemic effects of SWCNT under workplace or environmental exposure paradigms.
Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of ...hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosarcomas. Via both its core protein and heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in
lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor. There are several immunotherapeutic approaches to targeting GPC3, including vaccines, monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, cytolytic T lymphocytes, and CAR T cells. These therapies offer a potentially novel means to target these pediatric solid embryonal tumors. A key pediatric-specific consideration of GPC3-targeted immunotherapeutics is that GPC3 can be physiologically expressed in normal tissues during the first year of life, particularly in the liver and kidney. In summary, this article reviews the current evidence for targeting childhood cancers with GPC3-directed immunotherapies.
A chemical free, nanotechnology-based, antimicrobial platform using Engineered Water Nanostructures (EWNS) was recently developed. EWNS have high surface charge, are loaded with reactive oxygen ...species (ROS), and can interact-with, and inactivate an array of microorganisms, including foodborne pathogens. Here, it was demonstrated that their properties during synthesis can be fine tuned and optimized to further enhance their antimicrobial potential. A lab based EWNS platform was developed to enable fine-tuning of EWNS properties by modifying synthesis parameters. Characterization of EWNS properties (charge, size and ROS content) was performed using state-of-the art analytical methods. Further their microbial inactivation potential was evaluated with food related microorganisms such as Escherichia coli, Salmonella enterica, Listeria innocua, Mycobacterium parafortuitum, and Saccharomyces cerevisiae inoculated onto the surface of organic grape tomatoes. The results presented here indicate that EWNS properties can be fine-tuned during synthesis resulting in a multifold increase of the inactivation efficacy. More specifically, the surface charge quadrupled and the ROS content increased. Microbial removal rates were microorganism dependent and ranged between 1.0 to 3.8 logs after 45 mins of exposure to an EWNS aerosol dose of 40,000 #/cm(3).
Massive apoptosis of keratinocytes has been implicated in the pathogenesis of chemotherapy-induced skin toxicities, but the underlying mechanisms of action are not well understood. The present study ...investigated the apoptotic effect of doxorubicin (DOX) on HaCaT keratinocytes and determined the underlying mechanisms. Treatment of the cells with DOX induced reactive oxygen species (ROS) generation and a concomitant increase in apoptotic cell death through the mitochondrial death pathway independent of p53. Electron spin resonance and flow cytometry studies showed that superoxide is the primary oxidative species induced by DOX and responsible for the death inducing effect. Ectopic expression of mitochondrial superoxide scavenging enzyme (MnSOD) or treatment with MnSOD mimetic (MnTBAP) inhibited DOX-induced superoxide generation and apoptosis. The mechanism by which superoxide mediates the apoptotic effect of DOX was shown to involve downregulation of Bcl-2 through ubiquitin–proteasomal degradation. Superoxide induces dephosphorylation of Bcl-2 through MAP kinase ERK1/2 inactivation, which promotes ubiquitination of Bcl-2. We also provide evidence for the oxidative modification of ERK1/2 through cysteine sulfenic acid formation. These findings indicate a novel pathway for redox regulation of apoptosis regulatory proteins, which could be important in the understanding of chemotherapy-induced toxicities and development of preventive treatment strategies which are currently lacking.
Oxidative stress is a putative factor responsible for reducing function and increasing apoptotic signaling in skeletal muscle with aging. This study examined the contribution and functional ...significance of the xanthine oxidase enzyme as a potential source of oxidant production in aged skeletal muscle during repetitive in situ electrically stimulated isometric contractions. Xanthine oxidase activity was inhibited in young adult and aged mice via a subcutaneously placed time-release (2.5mg/day) allopurinol pellet, 7days before the start of in situ electrically stimulated isometric contractions. Gastrocnemius muscles were electrically activated with 20 maximal contractions for 3 consecutive days. Xanthine oxidase activity was 65% greater in the gastrocnemius muscle of aged mice compared to young mice. Xanthine oxidase activity also increased after in situ electrically stimulated isometric contractions in muscles from both young (33%) and aged (28%) mice, relative to contralateral noncontracted muscles. Allopurinol attenuated the exercise-induced increase in oxidative stress, but it did not affect the elevated basal level of oxidative stress that was associated with aging. In addition, inhibition of xanthine oxidase activity decreased caspase-3 activity, but it had no effect on other markers of mitochondrial-associated apoptosis. Our results show that compared to control conditions, suppression of xanthine oxidase activity by allopurinol reduced xanthine oxidase activity, H2O2 levels, lipid peroxidation, and caspase-3 activity; prevented the in situ electrically stimulated isometric contraction-induced loss of glutathione; prevented the increase in catalase and copper–zinc superoxide dismutase activities; and increased maximal isometric force in the plantar flexor muscles of aged mice after repetitive electrically evoked contractions.
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