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1.
Respir Res ; 25(1): 75, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317149

RESUMO

BACKGROUND: Electronic cigarettes (EC) have gained popularity, especially among young people, with the introduction of fourth-generation devices based on e-liquids containing nicotine salts that promise a smoother vaping experience than freebase nicotine. However, the toxicological effects of nicotine salts are still largely unknown, and the chemical diversity of e-liquids limits the comparison between different studies to determine the contribution of each compound to the cytotoxicity of EC aerosols. Therefore, the aim of this study was to evaluate the toxicological profile of controlled composition e-liquid aerosols to accurately determine the effects of each ingredient based on exposure at the air-liquid interface. METHODS: Human lung epithelial cells (A549) were exposed to undiluted aerosols of controlled composition e-liquids containing various ratios of propylene glycol (PG)/vegetable glycerin (VG) solvents, freebase nicotine, organic acids, nicotine salts, and flavoured commercial e-liquids. Exposure of 20 puffs was performed at the air-liquid interface following a standard vaping regimen. Toxicological outcomes, including cytotoxicity, inflammation, and oxidative stress, were assessed 24 h after exposure. RESULTS: PG/VG aerosols elicited a strong cytotoxic response characterised by a 50% decrease in cell viability and a 200% increase in lactate dehydrogenase (LDH) production, but had no effects on inflammation and oxidative stress. These effects occurred only at a ratio of 70/30 PG/VG, suggesting that PG is the major contributor to aerosol cytotoxicity. Both freebase nicotine and organic acids had no greater effect on cell viability and LDH release than at a 70/30 PG/VG ratio, but significantly increased inflammation and oxidative stress. Interestingly, the protonated form of nicotine in salt showed a stronger proinflammatory effect than the freebase nicotine form, while benzoic acid-based nicotine salts also induced significant oxidative stress. Flavoured commercial e-liquids was found to be cytotoxic at a threshold dose of ≈ 330 µg/cm². CONCLUSION: Our results showed that aerosols of e-liquids consisting only of PG/VG solvents can cause severe cytotoxicity depending on the concentration of PG, while nicotine salts elicit a stronger pro-inflammatory response than freebase nicotine. Overall, aerosols from fourth-generation devices can cause different toxicological effects, the nature of which depends on the chemical composition of the e-liquid.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adolescente , Nicotina/toxicidade , Vaping/efeitos adversos , Sais , Solventes , Propilenoglicol/toxicidade , Propilenoglicol/química , Glicerol/química , Glicerol/farmacologia , Aerossóis , Aromatizantes , Inflamação
2.
Environ Health Perspect ; 132(2): 26001, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38319881

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS. OBJECTIVES: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest. This work builds from the 2022 evidence map that collated evidence on a separate set of ∼150 PFAS. Like our previous work, this SEM does not include PFAS that are the subject of ongoing or completed assessments at the US EPA. METHODS: SEM methods were used to search, screen, and inventory mammalian bioassay and epidemiological literature from peer-reviewed and gray literature sources using manual review and machine-learning software. For each included study, study design details and health end points examined were summarized in interactive web-based literature inventories. Some included studies also underwent study evaluation and detailed extraction of health end point data. All underlying data is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 13,000 studies were identified from scientific databases. Screening processes identified 121 mammalian bioassay and 111 epidemiological studies that met screening criteria. Epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Mammalian bioassay evidence (available for 30 PFAS) commonly assessed effects in the reproductive, whole-body, nervous, and hepatic systems. Overall, 41 PFAS had evidence across mammalian bioassay and epidemiology data streams (roughly 11% of searched chemicals). DISCUSSION: No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search. Results from this SEM, our 2022 SEM on ∼150 PFAS, and other PFAS assessment products from the US EPA are compiled into a comprehensive PFAS dashboard that provides researchers and regulators an overview of the current PFAS human health landscape including data gaps and can serve as a scoping tool to facilitate prioritization of PFAS-related research and/or risk assessment activities. https://doi.org/10.1289/EHP13423.


Assuntos
Fluorocarbonos , Animais , Estados Unidos , Humanos , United States Environmental Protection Agency , Reprodução , Medição de Risco , Fluorocarbonos/toxicidade , Mamíferos
3.
Sci Rep ; 14(1): 3121, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326390

RESUMO

A response to manganese nanoparticles was studied in seedlings of two wheat cultivars and a model system of plant cell membranes. Nanoparticles at concentrations of 125 and 250 mg/ml were applied foliar. The application of NPs enhanced the content of Mn in plant cells, indicating its penetration through the leaf surface. The stressful effect in the plant cells was estimated based on changes in the activity of antioxidant enzymes, content of chlorophylls and starch. MnNPs evoked no significant changes in the leaf morphology, however, an increase in enzyme activity, starch accumulation, and a decrease in chlorophyll synthesis indicated the stress occurrence. Moreover, a rise in the electrokinetic potential of the chloroplast membrane surface and the reconstruction of their hydrophobic parts toward an increase in fatty acid saturation was found.


Assuntos
Manganês , Nanopartículas , Manganês/toxicidade , Manganês/metabolismo , Plântula/metabolismo , Triticum/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Clorofila/metabolismo , Nanopartículas/toxicidade , Nanopartículas/química , Membrana Celular/metabolismo , Amido/metabolismo
4.
Sci Rep ; 14(1): 3184, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326450

RESUMO

Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell's viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian 'Big Four' snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell's viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell's viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.


Assuntos
Mordeduras de Serpentes , Humanos , Animais , Naja naja , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Víboras/toxicidade , Elapidae , Venenos Elapídicos/farmacologia , Venenos Elapídicos/uso terapêutico , Mioblastos , Atrofia
5.
FASEB J ; 38(3): e23448, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38305779

RESUMO

Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver of diabetes-associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis, and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycemia across multiple tissues using single-cell RNA sequencing (scRNA-seq) and identified conserved, as well as organ-specific, changes associated with diabetes complications. By studying an early time point of diabetes, we focus on biological processes involved in the initiation of the disease, before the later organ-specific manifestations had supervened. We used a mouse model of type 1 diabetes and performed scRNA-seq on cells isolated from the heart, kidney, liver, and spleen of streptozotocin-treated and control male mice after 8 weeks and assessed differences in cell abundance, gene expression, pathway activation, and cell signaling across organs and within organs. In response to hyperglycemia, endothelial cells, macrophages, and monocytes displayed organ-specific transcriptional responses, whereas fibroblasts showed similar responses across organs, exhibiting altered metabolic gene expression and increased myeloid-like fibroblasts. Furthermore, we found evidence of endothelial dysfunction in the kidney, and of endothelial-to-mesenchymal transition in streptozotocin-treated mouse organs. In summary, our study represents the first single-cell and multi-organ analysis of early dysfunction in type 1 diabetes-associated hyperglycemia, and our large-scale dataset (comprising 67 611 cells) will serve as a starting point, reference atlas, and resource for further investigating the events leading to early diabetic disease.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Camundongos , Animais , Masculino , Diabetes Mellitus Tipo 1/genética , Células Endoteliais , Estreptozocina/toxicidade , Camundongos Endogâmicos C57BL , Hiperglicemia/genética , Análise de Sequência de RNA
6.
Philos Trans R Soc Lond B Biol Sci ; 379(1898): 20220510, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38310928

RESUMO

Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In this review, we will discuss the impacts of the chemical exposome complexity on the balance between detoxication and side effects. There is a large discrepancy between the limited number of proteins involved in these pathways (few dozens) and the diversity and complexity of the chemical exposome (tens of thousands of chemicals). Several XMP proteins have a low specificity which allows them to bind and/or metabolize a large number of chemicals. This leads to undesired consequences, such as cross-inhibition, inefficient metabolism, release of toxic intermediates, etc. Furthermore, several XMP proteins have endogenous functions that may be disrupted upon exposure to exogenous chemicals. The gut microbiome produces a very large number of metabolites that enter the body and are part of the chemical exposome. It can metabolize xenobiotics and either eliminate them or lead to toxic derivatives. The complex interactions between chemicals of different origins will be illustrated by the diverse roles of the aryl hydrocarbon receptor which binds and transduces the signals of a large number of xenobiotics, microbiome metabolites, dietary chemicals and endogenous compounds. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.


Assuntos
Expossoma , Microbioma Gastrointestinal , Animais , Xenobióticos/química , Xenobióticos/metabolismo , Xenobióticos/toxicidade , Inativação Metabólica , Receptores de Hidrocarboneto Arílico/metabolismo
7.
Sci Rep ; 14(1): 2868, 2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311636

RESUMO

The escalating presence of heavy metals (HMs) in the Panjkora River water and their impact on fish pose a significant challenge to both the ecological community and human health. Consequently, a study was conducted with the primary aim of elucidating their influence on human health-related issues. To address this, the concentrations of heavy metals, including arsenic (As), cadmium (Cd), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn), in both water and the fish species Crossocheilus diplocheilus were investigated across various locations within the study area. The quantification of HMs concentration was carried out utilizing an atomic absorption spectrophotometer. The highest concentration in water was found as 0.060 mg/L for Pb and lowest for Fe, whereas the highest concentration in fish was 2.028 mg/kg for Pb and lowest for As. Human health risk associated with fish eating was evaluated by using health risk indices (HRI) for non-carcinogenic health risks and targeted cancer risk (TR) for carcinogenic health risks. The values of the health risk index (HRI) were found greater than 1 except Fe (0.0792), Zn (0.782), and Mn (0.541). The highest mean HRI > 1 was recorded for As (62.99), Cd (26.85), and Pb (10.56). This implies that fish consumption from river Panjkora is not safe up to some extent. Similarly, the TR value for As, Cd, and Pb was found 2.8 [Formula: see text], 1.6 [Formula: see text], 2.8 ×[Formula: see text] which showed cancer risk. There is a detected risk to human health associated with the consumption of fish from the Panjkora River. The government must implement adaptive measures to address this significant issue of water pollution in the study area. Additionally, there is a need for further extensive and prolonged research studies in this context.


Assuntos
Arsênio , Metais Pesados , Neoplasias , Poluentes Químicos da Água , Animais , Humanos , Qualidade da Água , Cádmio , Chumbo , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Arsênio/toxicidade , Arsênio/análise , Manganês , Rios , Peixes , Medição de Risco
8.
Part Fibre Toxicol ; 21(1): 4, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311718

RESUMO

BACKGROUND: Micro- and nanoplastics (MNPs) represent one of the most widespread environmental pollutants of the twenty-first century to which all humans are orally exposed. Upon ingestion, MNPs pass harsh biochemical conditions within the gastrointestinal tract, causing a unique protein corona on the MNP surface. Little is known about the digestion-associated protein corona and its impact on the cellular uptake of MNPs. Here, we systematically studied the influence of gastrointestinal digestion on the cellular uptake of neutral and charged polystyrene MNPs using THP-1-derived macrophages. RESULTS: The protein corona composition was quantified using LC‒MS-MS-based proteomics, and the cellular uptake of MNPs was determined using flow cytometry and confocal microscopy. Gastrointestinal digestion resulted in a distinct protein corona on MNPs that was retained in serum-containing cell culture medium. Digestion increased the uptake of uncharged MNPs below 500 nm by 4.0-6.1-fold but did not affect the uptake of larger sized or charged MNPs. Forty proteins showed a good correlation between protein abundance and MNP uptake, including coagulation factors, apolipoproteins and vitronectin. CONCLUSION: This study provides quantitative data on the presence of gastrointestinal proteins on MNPs and relates this to cellular uptake, underpinning the need to include the protein corona in hazard assessment of MNPs.


Assuntos
Microplásticos , Coroa de Proteína , Humanos , Microplásticos/toxicidade , Coroa de Proteína/química , Coroa de Proteína/metabolismo , Poliestirenos/toxicidade , Plásticos , Digestão
9.
J Wound Care ; 33(Sup2a): xxxii-xl, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324419

RESUMO

OBJECTIVE: Chlorhexidine-iodophor (CHX-IP) composite solution is a polymer of chlorhexidine and iodophor produced with new technology, for use in diabetic foot infection. However, the effect of CHX-IP on the growth activity of fibroblasts remains unknown, thus the effects of different concentrations of CHX-IP composite solution on the viability and micromorphology of human skin fibroblasts were studied in vitro cell culture in this study. METHOD: A cell viability assay was applied to calculate cell viability and an inverted fluorescence microscope was used to observe cell morphology over five days. RESULTS: The results showed that the toxic effect of CHX-IP on fibroblasts was solution concentration-dependent and decreased over time. When the concentration of CHX-IP was 5.0mg/ml, 2.5mg/ml, 0.625mg/ml, 0.15625mg/ml, 0.078125mg/ml or 0mg/ml, the difference of optical density (OD) value on different days was statistically significant (p<0.05). There were statistically significant differences in the OD value of fibroblasts among different concentrations of CHX-IP on: day 2 (F=4.809, p=0.004); day 3 (F=21.508, p<0.001); day 4 (F=63.952, p<0.001); and day 5 (F=160.407, p<0.001). In addition, a concentration of 5.0mg/ml CHX-IP resulted in a fibroblastic viability rate of 0% on day 4, when CHX-IP was diluted to 2.5mg/ml or 1.25 mg/ml, fibroblastic viability rate decreased to 0% day 5. However, when the CHX-IP was diluted to 0.15625mg/ml or 0.078125mg/ml, the fibroblastic cell viability rate increased slightly on day 5. The morphology of cells observed under microscope indirectly supported this result. CONCLUSION: The findings of this study showed that the toxic effect of CHX-IP on fibroblasts was solution concentration-dependent and decreased over time.


Assuntos
Anti-Infecciosos Locais , Clorexidina , Humanos , Clorexidina/farmacologia , Anti-Infecciosos Locais/toxicidade , Iodóforos/farmacologia , Pele , Fibroblastos
10.
Hum Exp Toxicol ; 43: 9603271241231947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324556

RESUMO

Objectives: Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers, such as solid tumors, leukemia, lymphomas and breast cancer. It can also cause injuries to multiple organs, including the heart, liver, and brain or kidney, although cardiotoxicity is the most prominent side effect of DOX. In this study, we examined the potential effects of DOX on autophagy activity in two different mouse fibroblasts.Methods: Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX to assess changes in the expression of two commonly used autophagy protein markers, LC3II and p62. We also examined the effects of DOX the on expression of key genes that encode components of the molecular machinery and regulators modulating autophagy in response to both extracellular and intracellular signals.Results: We observed that LC3II levels increased and p62 levels decreased following the DOX treatment in NIH3T3 cells. However, similar effects were not observed in primary cardiac fibroblasts. In addition, DOX treatment induced the upregulation of a significant number of genes involved in autophagy in NIH3T3 cells, but not in primary cardiac fibroblasts.Conclusions: Taken together, these results indicate that DOX upregulates autophagy in fibroblasts in a cell-specific manner.


Assuntos
Estresse Oxidativo , Transdução de Sinais , Humanos , Criança , Animais , Camundongos , Células NIH 3T3 , Fibroblastos , Doxorrubicina/toxicidade , Autofagia , Cardiotoxicidade/metabolismo , Miócitos Cardíacos/metabolismo , Apoptose
11.
J Toxicol Environ Health A ; 87(8): 342-356, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38310537

RESUMO

The assessment of amphibian responses as bioindicators of exposure to chemical pollutants is an important tool for conservation of native species. This study aimed to investigate the effects of chronic aluminum (Al) and zinc (Zn) exposure on survival, body size, morphology (malformations), and immune system (leukocyte profile) in P. cuvieri tadpoles. Ecotoxicological analyses were performed utilizing chronic toxicity tests in which 210 tadpoles at the 25th Gosner developmental stage were exposed to Al and Zn. Individuals of P. cuvieri were maintained in glass containers containing various concentrations of aluminum sulfate (0.1, 0.2, or 0.3 mg/L) and zinc sulfate (0.18, 0.27 or 0.35 mg/L), and tests were performed in triplicate. After 14 days, amphibians were weighed, measured and survival rate, malformations in the oral and intestine apparatus, leukocyte profile, and ratio between neutrophils and lymphocytes determined. The differing concentrations of Al and Zn did not produce lethality in P. cuvieri where 95% of the animals survived 326 hr following metal exposure. Individuals exposed to Zn achieved greater body growth and weight gain compared to controls. Aluminum increased weight gain compared controls. These metals also produced malformations of the oral and intestine apparatus and enhanced occurrence of hemorrhages, especially at the highest doses. Lymphocytes were the predominant cells among leukocytes, with lymphopenia and neutrophilia observed following Al and Zn treatment, as evidenced by elevated neutrophil/lymphocyte ratio, an important indicator of stress in animals. Data suggest that further studies need to be carried out, even with metal concentrations higher than those prescribed by CONAMA, to ensure the conservation of this species.


Assuntos
Poluentes Químicos da Água , Zinco , Humanos , Animais , Zinco/farmacologia , Zinco/toxicidade , Alumínio/farmacologia , Larva , Anuros/fisiologia , Metais , Sistema Imunitário/química , Tamanho Corporal , Aumento de Peso , Poluentes Químicos da Água/toxicidade
12.
Mol Biol Rep ; 51(1): 277, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319443

RESUMO

BACKGROUND: The most widely used food additive monosodium glutamate (MSG) has been linked to immunopathology. Conversely, quercetin (Q), a naturally occurring flavonoid has been demonstrated to have immunomodulatory functions. Therefore, the purpose of the study is to determine if quercetin can mitigate the deleterious effects of MSG on immune cells, and the possible involvement of TLR, if any.  METHODS AND RESULTS: This study was conducted on Q, to determine how it affects the inflammatory response triggered by MSG in primary cultured thymocytes and splenocytes from rats (n = 5). Q shielded cells by augmenting cell survival and decreasing lactate dehydrogenase leakage during MSG treatment. It decreased IL-1ß, IL-6, IL-8, and TNF-α expression and release by hindering NF-kB activation and by inhibiting the JAK/STAT pathway. Moreover, Q prevented NLRP3 activation, lowered IL-1ß production, and promoted an anti-inflammatory response by increasing IL-10 production. Q reduced MSG-induced cellular stress and inflammation by acting as an agonist for PPAR-γ and LXRα, preventing NF-kB activation, and lowering MMP-9 production via increasing TIMP-1. Additionally, Q neutralized free radicals, elevated intracellular antioxidants, and impeded RIPK3, which is involved in inflammation induced by oxidative stress, TNF-α, and TLR agonists in MSG-treated cells. Furthermore, it also modulated TYK2 and the JAK/STAT pathway, which exhibited an anti-inflammatory effect. CONCLUSIONS: MSG exposure is associated with immune cell dysfunction, inflammation, and oxidative stress, and Q modulates TLR to inhibit NF-kB and JAK/STAT pathways, providing therapeutic potential. Further research is warranted to understand Q's downstream effects and explore its potential clinical applications in inflammation.


Assuntos
NF-kappa B , Transdução de Sinais , Animais , Ratos , Anti-Inflamatórios , Inflamação/induzido quimicamente , Janus Quinases , Quercetina/farmacologia , Glutamato de Sódio/toxicidade , Baço , Fatores de Transcrição STAT , Timócitos , Fator de Necrose Tumoral alfa
13.
J Glob Health ; 14: 04032, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38299774

RESUMO

*Joint senior authorship. BACKGROUND: Previous studies have observed the adverse effects of ambient fine particulate matter pollution (PM2.5) on heart failure (HF). However, evidence regarding the impacts of specific PM2.5 components remains scarce. METHODS: We included 58 129 patients hospitalised for HF between 2013 and 2017 in 11 cities of Shanxi, China from inpatient discharge database. We evaluated exposure to PM2.5 and its components ((sulphate (SO42-), nitrate (NO3-), ammonium (NH4+), organic matter (OM) and black carbon (BC)), along with meteorological factors using bilinear interpolation at each patients' residential address. We used multivariable logistic and linear regression models to assess the associations of these components with in-hospital case fatality, hospital expenses, and length of hospital stay. RESULTS: Increase equivalents to the interquartile range (IQR) in OM (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.02, 1.26) and BC (OR = 1.14; 95% CI = 1.02, 1.26) were linked to in-hospital case fatality. Per IQR increments in PM2.5, SO42-, NO3-, OM, and BC were associated with cost increases of 420.62 (95% CI = 285.75, 555.49), 221.83 (95% CI = 96.95, 346.71), 214.93 (95% CI = 68.66, 361.21), 300.06 (95% CI = 176.96, 423.16), and 303.09 (95% CI = 180.76, 425.42) CNY. Increases of 1 IQR in PM2.5, SO42-, OM, and BC were associated with increases in length of hospital stay of 0.10 (95% CI = 0.02, 0.19), 0.09 (95% CI = 0.02, 0.17), 0.10 (95% CI = 0.03, 0.17), and 0.16 (95% CI = 0.08, 0.23) days. CONCLUSIONS: Our findings suggest that ambient SO42-, OM, and BC might be significant risk factors for HF, emphasising the importance of formulating customised guidelines for the chemical constituents of PM and controlling the emissions of the most dangerous components.


Assuntos
Poluentes Atmosféricos , Insuficiência Cardíaca , Humanos , Material Particulado/toxicidade , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Tempo de Internação , China/epidemiologia , Exposição Ambiental/efeitos adversos
14.
JAMA Netw Open ; 7(2): e2354298, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38300617

RESUMO

Importance: With new legal abortion restrictions, timing of prenatal care initiation is critical to allow for discussion of reproductive options among pregnancies exposed to teratogenic medications. Objective: To investigate the prevalence of prenatal exposure to teratogenic medications and prenatal care initiation across gestational weeks. Design, Setting, and Participants: This descriptive, population-based cross-sectional study used health encounter data from a national sample of individuals with employer-sponsored health insurance. A validated algorithm identified pregnancies among persons identifying as female that ended with a live or nonlive outcome between January 2017 and December 2019. Data were analyzed from December 2022 to December 2023. Exposures: Prenatal exposure to any of 137 teratogenic medications, measured via pharmacy and medical claims. Measurement of prenatal care initiation was adapted from the Children's Health Care Quality Measures. Main Outcomes and Measures: Prevalence of prenatal exposure to teratogens and prenatal care initiation by gestational week. Timing of prenatal teratogenic exposure was compared with timing of prenatal care initiation and legal abortion cutoffs. Results: Among 639 994 pregnancies, 472 472 (73.8%; 95% CI, 73.7%-73.9%) had a live delivery (mean [SD] age, 30.9 [5.4] years) and 167 522 (26.2%; 95% CI, 26.1%-26.3%) had a nonlive outcome (mean [SD] age, 31.6 [6.4] years). Of pregnancies with live deliveries, 5.8% (95% CI, 5.7%-5.8%) were exposed to teratogenic medications compared with 3.1% (95% CI, 3.0%-3.2%) with nonlive outcomes. Median time to prenatal care was 56 days (IQR, 44-70 days). By 6 weeks' gestation, 8186 pregnancies had been exposed to teratogenic medications (25.2% [95% CI, 24.7%-25.7%] of pregnancies exposed at any time during gestation; 1.3% [95% CI, 1.3%-1.3%] of all pregnancies); in 6877 (84.0%; 95% CI, 83.2%-84.8%), prenatal care was initiated after 6 weeks or not at all. By 15 weeks, teratogenic exposures had occurred for 48.9% (95% CI, 48.4%-49.5%) of all teratogen-exposed pregnancies (2.5% [2.4-2.5] of all pregnancies); prenatal care initiation occurred after 15 weeks for 1810 (16.8%; 95% CI, 16.1%-17.5%) with live deliveries and 2975 (58.3%; 95% CI, 56.9%-59.6%) with nonlive outcomes. Teratogenic medications most used within the first 15 gestational weeks among live deliveries included antiinfectives (eg, fluconazole), anticonvulsants (eg, valproate), antihypertensives (eg, lisinopril), and immunomodulators (eg, mycophenolate). For nonlive deliveries, most antihypertensives were replaced by vitamin A derivatives. Conclusions and Relevance: In this cross-sectional study, most exposures to teratogenic medications occurred in early pregnancy and before prenatal care initiation, precluding prenatal risk-benefit assessments. Prenatal care commonly occurred after strict legal abortion cutoffs, prohibiting consideration of pregnancy termination if concerns about teratogenic effects arose.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Teratógenos , Gravidez , Criança , Feminino , Humanos , Adulto , Teratógenos/toxicidade , Anti-Hipertensivos , Estudos Transversais , Cuidado Pré-Natal
15.
Sci Rep ; 14(1): 2835, 2024 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310166

RESUMO

Guangxi, China, is one of the world's largest karst regions where potential toxic elements tend to accumulate, resulting in high soil background values. This study explores the ecological risk, elemental baseline values, and sources of potential toxic elements in karst regions, expanding the research to include 21 common elements. The significance of this research lies in its implications for the management of potential toxic element pollution, the formulation of environmental quality standards, and soil remediation in karst areas. In this study, 12,547 topsoil samples (0-20 cm) were collected in the study area. Pollution assessment and ecological risk evaluation of eight potential toxic elements (Zn, Ni, Cu, Pb, Cd, Hg, Cr, and As) were conducted using the geo-accumulation index method and potential ecological risk index method. Multivariate statistical analysis was applied to analyze the total content of 21 common elements (Zn, Ni, Cu, Pb, P, Cd, Hg, Co, Mn, Cr, V, I, S, As, pH, Se, N, CaO, Corg, Mo, and F). Additionally, the potential sources of 21 soil elements were preliminarily quantitatively analyzed using the principal component analysis-absolute principal component scores-multiple linear regression receptor model. The results showed that (1) Zn, Ni, Cu, Pb, Cd, Cr, V, and As were enriched in the research area and Ca, Cd, Mn, Mo, Hg, As, and Cu might have been influenced by human activities; (2) Cr, Pb, As, and Zn were generally lightly polluted, with Hg having a moderate potential ecological risk level; and (3) Ni and Zn have contributions of 37.99% and 35.07% from geological sources, agricultural fertilization, and pesticides. Mo, V, Cr, Se, Hg, and As exhibit contributions ranging from 39.44 to 59.22% originating from geological backgrounds and human activities. Corg, S, N, and P show contributions of 45.39% to 80.33% from surface vegetation. F, Co, Mn, and Pb have contributions ranging from 31.63 to 47.93% from acidic rocks in the soil parent material, mining activities, and transportation. Cd and CaO derive 31.67% and 40.23%, respectively, from soil parent material and industrial sources. I has 31.94% from geological background and human activities, and 31.95% from soil parent material and atmospheric sources. Cu has 30.56% from geological sources. The study results can serve as a scientific basis for element research in karst areas domestically and internationally.


Assuntos
Arsênio , Mercúrio , Metais Pesados , Poluentes do Solo , Humanos , Arsênio/toxicidade , Arsênio/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Cádmio/análise , Chumbo/análise , Monitoramento Ambiental/métodos , China , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Solo/química , Mercúrio/análise , Medição de Risco
16.
PeerJ ; 12: e16795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313003

RESUMO

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, choline-acetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models.


Assuntos
Produtos Biológicos , Transtornos da Memória , NF-kappa B , Animais , Ratos , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Lipopolissacarídeos/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , NF-kappa B/metabolismo , Produtos Biológicos/farmacologia
17.
Methods Mol Biol ; 2769: 15-25, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315386

RESUMO

Diethylnitrosamine (DEN) is a chemical hepatocarcinogenic agent that triggers a large array of oncogenic mutations after a single injection. Initiated hepatocytes subsequently undergo clonal expansion within a proliferative environment, rendering the DEN model a comprehensive carcinogen. In rodent studies, DEN finds extensive utility in experimental liver cancer research, mimicking several aspects of human hepatocellular carcinoma (HCC), including angiogenesis, metabolic reprogramming, immune exhaustion, and the ability to metastasize. Beyond the wealth of scientific insights gleaned from this model, the objective of this chapter is to review morphological, genomic, and immunological characteristics associated to DEN-induced HCC. Furthermore, this chapter provides a detailed procedural guide to effectively induce hepatocarcinogenesis in mice through a single intraperitoneal injection of DEN.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Humanos , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Hepatócitos/patologia , Camundongos Endogâmicos C57BL
18.
Methods Mol Biol ; 2769: 27-55, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315387

RESUMO

The hepatotoxic N-nitroso compound diethylnitrosamine (DEN) administered intraperitoneally (i.p.) induces liver neoplasms in rodents that reproducibly recapitulate some aspects of human hepatocarcinogenesis. In particular, DEN drives the stepwise formation of pre-neoplastic and neoplastic (benign or malignant) hepatocellular lesions reminiscent of the initiation-promotion-progression sequence typical of chemical carcinogenesis. In humans, the development of hepatocellular carcinoma (HCC) is also a multi-step process triggered by continuous hepatocellular injury, chronic inflammation, and compensatory hyperplasia that fuel the emergence of dysplastic liver lesions followed by the formation of early HCC. The DEN-induced liver tumorigenesis model represents a versatile preclinical tool that enables the study of many tumor development modifiers (genetic background, gene knockout or overexpression, diets, pollutants, or drugs) with a thorough follow-up of the multistage process on live animals by means of high-resolution imaging. Here, we provide a comprehensive protocol for the induction of hepatocellular neoplasms in wild-type C57BL/6J male mice following i.p. DEN injection (25 mg/kg) at 14 days of age and 36 weeks feeding of a high-fat high-sucrose (HFHS) diet. We emphasize the use of ultrasound liver imaging to follow tumor development and provide histopathological correlations. We also discuss the extrinsic and intrinsic factors known to modify the course of liver tumorigenesis in this model.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Camundongos , Animais , Lactente , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/diagnóstico por imagem , Dietilnitrosamina/toxicidade , Camundongos Endogâmicos C57BL , Carcinogênese/patologia , Dieta Hiperlipídica/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Ultrassonografia
19.
Methods Mol Biol ; 2769: 57-65, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315388

RESUMO

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). Obesity is a known risk factor of NASH, which, in turn, increases the risk of developing cirrhosis (liver scarring) and hepatocellular carcinoma (HCC). In addition to being a potentially life-threatening condition, public health concerns surrounding NASH are amplified by the lack of FDA-approved treatments. Although various preclinical models reflecting both the histopathology and the pathophysiological progression of human NASH exist, most of these models are diet-based and require 6-13 months for NASH symptom manifestation. Here, we describe a simple and rapid-progression model of NASH and NASH-driven HCC in mice. Mice received a western diet equivalent (WD; i.e., a high-fat, high-fructose, and high-cholesterol diet), high-sugar water (23.1 g/L fructose and 18.9 g/L glucose), and weekly intraperitoneal injections of carbon tetrachloride (CCl4) at a dose of 0.2 µL/g of body weight. The resulting phenotype, consisting in liver fibrosis and HCC, appeared within 24 weeks of diet/treatment initiation and presented similar histological and transcriptomic features as human NASH and NASH-driven HCC, thereby supporting the adequacy of this preclinical model for the development and evaluation of drugs that can prevent or reverse these diseases.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Carcinoma Hepatocelular/genética , Tetracloreto de Carbono/toxicidade , Neoplasias Hepáticas/patologia , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Cirrose Hepática/patologia , Frutose , Dieta Hiperlipídica/efeitos adversos , Fígado/patologia , Camundongos Endogâmicos C57BL
20.
Hum Exp Toxicol ; 43: 9603271241231945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38316638

RESUMO

This study examined the impact of mercury (Hg) vapor exposure from amalgams among all American pregnant women. Amalgam-Hg vapor exposure among 1,665,890 weighted-pregnant women (n = 37) was examined in the 2015-2020 National Health and Nutrition Examination Survey (NHANES). Correlation coefficients between amalgam surfaces and daily micrograms (µg) of urinary Hg excretion and daily µg of Hg vapor exposure from amalgams per kilogram (Kg) bodyweight were calculated. Daily Hg vapor exposure from amalgams was compared to Hg vapor safety limits. About 600,000 pregnant women (∼36%) had at least one amalgam surface. Median daily urinary Hg excretion was ∼2.5-fold higher among pregnant women with amalgams as compared to pregnant women without amalgams. A significant correlation was observed between the number of amalgam surfaces and daily urinary Hg excretion. Among pregnant women with amalgams, it was estimated that the median daily Hg vapor dose from amalgams was 7.66 µg of Hg and 0.073 µg of Hg/Kg bodyweight. Among all pregnant women, ∼28% received daily Hg vapor doses from amalgams above the least restrictive United States (US) Environmental Protection Agency (EPA) safety limit and ∼36% received above the most restrictive California (CA) EPA safety limit. Given the potential for fetal toxicological effects from prenatal Hg vapor exposure, special emphasis needs to be placed on reducing/eliminating amalgams in pregnancy/women of reproductive age and future studies should evaluate adverse pregnancy outcomes.


Assuntos
Mercúrio , Gestantes , Humanos , Feminino , Gravidez , Inquéritos Nutricionais , Mercúrio/toxicidade , Amálgama Dentário
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