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1.
Sci Total Environ ; 932: 172987, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38734084

RESUMO

Liquid crystal monomers (LCMs) are emerging contaminants characterized by their persistence, bioaccumulation potential, and toxicity. They have been observed in several environmental matrices associated with electronic waste (e-waste) dismantling activities, particularly in China. However, there is currently no information on the pollution caused by LCMs in other developing countries, such as Pakistan. In this study, we collected soil samples (n = 59) from e-waste dismantling areas with different functions in Pakistan for quantification analysis of 52 target LCMs. Thirty out of 52 LCMs were detected in the soil samples, with the concentrations ranging from 2.14 to 191 ng/g (median: 16.3 ng/g), suggesting widespread contamination by these emerging contaminants. Fluorinated LCMs (median: 10.4 ng/g, range: 1.27-116 ng/g) were frequently detected and their levels were significantly (P < 0.05) higher than those of non-fluorinated LCMs (median: 6.11 ng/g, range: not detected (ND)-76.7 ng/g). The concentrations and profiles of the observed LCMs in the soil samples from the four functional areas varied. The informal dismantling of e-waste poses a potential exposure risk to adults and infants, with median estimated daily intake (EDI, ng/kg bw/day) values of 0.0420 and 0.1013, respectively. Calculation of the hazard quotient (HQ) suggested that some LCMs (e.g., ETFMBC (1.374) and EDFPB (1.257)) may pose potential health risks to occupational workers and their families. Considering the widespread contamination and risks associated with LCMs, we strongly recommend enhancing e-waste management and regulation in Pakistan.


Assuntos
Resíduo Eletrônico , Monitoramento Ambiental , Cristais Líquidos , Poluentes do Solo , Paquistão , Resíduo Eletrônico/análise , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Humanos , Exposição Ambiental/estatística & dados numéricos , Medição de Risco
2.
J Mol Cell Cardiol ; 192: 79-93, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761990

RESUMO

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.


Assuntos
Ferroptose , Técnicas de Silenciamento de Genes , Sobrecarga de Ferro , Lipocalina-2 , Miocárdio , RNA Longo não Codificante , Sepse , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Ferroptose/genética , Sepse/complicações , Sepse/genética , Sepse/metabolismo , Camundongos , Lipocalina-2/metabolismo , Lipocalina-2/genética , Masculino , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/complicações , Miocárdio/metabolismo , Miocárdio/patologia , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Regulação da Expressão Gênica , Ferro/metabolismo , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/metabolismo , Traumatismos Cardíacos/genética , Perfilação da Expressão Gênica
4.
Environ Int ; 186: 108609, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38579452

RESUMO

Recently, evidence of aromatic amine antioxidants (AAs) existence in the dust of the electronic waste (e-waste) dismantling area has been exposed. However, there are limited studies investigating occupational exposure and toxicity associated with AAs and their transformation products (p-phenylenediamines-quinones, i.e., PPD-Qs). In this study, 115 dust and 42 hand wipe samples collected from an e-waste recycling industrial park in central China were analyzed for 19 AAs and 6 PPD-Qs. Notably, the median concentration of ∑6PPD-Qs (1,110 ng/g and 1,970 ng/m2) was significantly higher (p < 0.05, Mann-Whitney U test) than that of ∑6PPDs (147 ng/g and 34.0 ng/m2) in dust and hand wipes. Among the detected analytes, 4-phenylaminodiphenylamine quinone (DPPD-Q) (median: 781 ng/g) and 1,4-Bis(2-naphthylamino) benzene quinone (DNPD-Q) (median: 156 ng/g), were particularly prominent, which were first detected in the e-waste dismantling area. Occupational exposure assessments and nuclear receptor interference ability, conducted through estimated daily intake (EDI) and molecular docking analysis, respectively, indicated significant occupational exposure to PPD-Qs and suggested prioritized Liver X receptors (LXRs) disruption potential of PPDs and PPD-Qs. The study provides the first evidence of considerable levels of AAs and PPD-Qs in the e-waste-related hand wipe samples and underscores the importance of assessing occupational exposure and associated toxicity effects.


Assuntos
Antioxidantes , Poeira , Resíduo Eletrônico , Exposição Ocupacional , Reciclagem , Exposição Ocupacional/análise , Humanos , Poeira/análise , China , Quinonas/análise , Aminas/análise
5.
Sci Total Environ ; 924: 171607, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461993

RESUMO

Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of ∑mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in ∑mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.


Assuntos
Dietilexilftalato , Poluentes Ambientais , Hepatopatia Gordurosa não Alcoólica , Ácidos Ftálicos , Humanos , Masculino , Ratos , Animais , Dietilexilftalato/metabolismo , Exposição Ambiental , Ratos Wistar , Ácidos Ftálicos/urina , Poluentes Ambientais/metabolismo , Biomarcadores
6.
Environ Sci Technol ; 58(8): 3908-3918, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38329000

RESUMO

The heterogeneous photodegradation behavior of liquid crystal monomers (LCMs) in standard dust (standard reference material, SRM 2583) and environmental dust was investigated. The measured photodegradation ratios for 23 LCMs in SRM and environmental dust in 12 h were 11.1 ± 1.8 to 23.2 ± 1.1% and 8.7 ± 0.5 to 24.0 ± 2.8%, respectively. The degradation behavior of different LCM compounds varied depending on their structural properties. A quantitative structure-activity relationship model for predicting the degradation ratio of LCMs in SRM dust was established, which revealed that the molecular descriptors related to molecular polarizability, electronegativity, and molecular mass were closely associated with LCMs' photodegradation. The photodegradation products of the LCM compound 4'-propoxy-4-biphenylcarbonitrile (PBIPHCN) in dust, including •OH oxidation, C-O bond cleavage, and ring-opening products, were identified by nontarget analysis, and the corresponding degradation pathways were suggested. Some of the identified products, such as 4'-hydroxyethoxy-4-biphenylcarbonitrile, showed predicted toxicity (with an oral rat lethal dose of 50%) comparable to that of PBIPHCN. The half-lives of the studied LCMs in SRM dust were estimated at 32.2-82.5 h by fitting an exponential decay curve to the observed photodegradation data. The photodegradation mechanisms of LCMs in dust were revealed for the first time, enhancing the understanding of LCMs' environmental behavior and risks.


Assuntos
Poeira , Cristais Líquidos , Animais , Ratos , Relação Quantitativa Estrutura-Atividade , Fotólise
7.
Arch Biochem Biophys ; 754: 109923, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408533

RESUMO

BACKGROUND: Sepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. METHODS: Adult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1ß, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. RESULTS: Compared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1ß and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1ß, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1ß and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1ß protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). CONCLUSION: Apoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.


Assuntos
Sepse , Fator de Necrose Tumoral alfa , Camundongos , Animais , Masculino , Piroptose , Caspase 3 , Espécies Reativas de Oxigênio , Aldeído-Desidrogenase Mitocondrial , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Apoptose , Sepse/complicações , Sepse/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2
8.
J Hazard Mater ; 468: 133835, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394895

RESUMO

While N, N'-substituted p-phenylenediamines (PPDs) and their quinone derivatives (PPDQs) have been widely detected in the environment, there is currently limited data on their occurrence in humans. In this study, we conducted the first serum analysis of two PPDs and PPDQs in the healthy and secondary nonalcoholic fatty liver disease (S-NAFLD) cohorts in South China. The concentrations of four oxidative stress biomarkers (OSBs), namely, 8-iso-prostaglandin F2α (8-PGF2α), 11ß-prostaglandin F2α (11-PGF2α), 15(R)-prostaglandin F2α (15-PGF2α), and 8-hydroxy-2'-deoxyguanosine in serum samples were also measured. Results showed that N-(1,3-dimethybutyl)-N'-phenyl-p-phenylenediamine (6PPD) quinone was the predominant target analytes both in the healthy and S-NAFLD cohorts, with the median concentrations of 0.13 and 0.20 ng/mL, respectively. Significant (p < 0.05) and positive correlations were found between 6PPD concentration and 8-PGF2α, 11-PGF2α, and 15-PGF2α in both the healthy and S-NAFLD cohorts, indicating that 6PPD may be associated with lipid oxidative damage. In addition, concentrations of 6PPD in serum were associated significantly linked with total bilirubin (ß = 0.180 µmol/L, 95%CI: 0.036-0.396) and direct bilirubin (DBIL, ß = 0.321 µmol/L, 95%CI: 0.035-0.677) related to hepatotoxicity. Furthermore, 8-PGF2α, 11-PGF2α, and 15-PGF2α mediated 17.1%, 24.5%, and 16.6% of 6PPD-associated DBIL elevations, respectively. Conclusively, this study provides novel insights into human exposure to and hepatotoxicity assessment of PPDs and PPDQs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatia Gordurosa não Alcoólica , Humanos , Quinonas/toxicidade , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Bilirrubina , Prostaglandinas , Fenilenodiaminas/toxicidade
9.
Lancet ; 403(10423): 247, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245244
10.
Front Med (Lausanne) ; 10: 1289180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38076242

RESUMO

Background: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst. Results: We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT. Conclusion: Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, CRD42023412467.

11.
Eco Environ Health ; 2(3): 131-141, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38074986

RESUMO

Liquid crystal monomers (LCMs) are a family of synthetic organic chemicals applied in the liquid crystal displays (LCDs) of various electric and electronic products (e-products). Due to their unique properties (i.e., persistence, bioaccumulative potential, and toxicity) and widespread environmental distributions, LCMs have attracted increasing attention across the world. Recent studies have focused on the source, distribution, fate, and toxicity of LCMs; however, a comprehensive review is scarce. Herein, we highlighted the persistence and bioaccumulation potential of LCMs by reviewing their physical-chemical properties. The naming rules were suggested to standardize the abbreviations regarding LCMs. The sources and occurrences of LCMs in different environmental compartments, including dust, sediment, soil, leachate, air and particulate, human serum, and biota samples, were reviewed. It is concluded that the LCMs in the environment mainly originate from the usage and disassembly of e-products with LCDs. Moreover, the review of the potential recycling and removal technologies regarding LCMs from waste LCD panels suggests that a combination of natural attenuation and physic-chemical remediation should be developed for LCMs remediations in the future. By reviewing the health risks and toxicity of LCMs, it is found that a large gap exists in their toxicity and risk to organisms. The fate and toxicity investigation of LCMs, and further investigations on the effects on the human exposure risks of LCMs to residents, especially to occupational workers, should be considered in the future.

12.
Cancer Med ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38133525

RESUMO

BACKGROUND: Typical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment-free remission (TFR). METHODS: We conducted a literature review of current developments of treatment-free remission and molecular monitoring methods. RESULTS: More effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies. CONCLUSION: Currently, predictive indicators for treatment-free remission outcomes and recurrence are lacking in clinical practice. In future, treatment-free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment-free remission.

13.
Front Public Health ; 11: 1272149, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026403

RESUMO

Background: Seasons were found to be related to the occurrences of venous thromboembolism (VTE) in hospitalized patients. No previous study has explored whether seasons were associated with VTE risk in pregnant women. This study aimed to investigate the relationships between the season of delivery and VTE risk during hospitalization among pregnant women. Methods: This is a multi-center retrospective cohort study of pregnant women. Participants were those who delivered at seven designated sites in Hubei Province, China, during the period from January 2017 to December 2022. They were categorized according to their season/month of delivery. Information on new-onset VTE during hospitalization was followed. Results: Approximately 0.28% (104/37,778) of the pregnant women developed new-onset VTE during hospitalization for delivery. After adjustment, compared with participants in the spring group, participants in the summer, autumn, and winter groups had an increased risk of VTE during hospitalization. The ORs were 2.59 [1.30, 5.15], 2.83 [1.43, 5.60], and 2.35 [1.17, 4.75] for the summer, autumn, and winter groups, respectively. Pregnant women in the combined group (summer + autumn + winter) had an increased risk of VTE during hospitalization than those in the spring group (OR, 2.59 [1.39, 4.85]). By restricting the analyses among pregnant women without in vitro fertilization, gestational diabetes mellitus, and preterm, the results still remained robust. Compared with participants who delivered in March, April, and May, participants who delivered in June, July, September, November, December, and February had a higher risk of VTE during hospitalization. Conclusion: This study demonstrated that pregnant women who delivered in summer, autumn, and winter had an increased VTE risk during hospitalization compared with those who delivered in spring.


Assuntos
Tromboembolia Venosa , Recém-Nascido , Humanos , Feminino , Gravidez , Tromboembolia Venosa/epidemiologia , Gestantes , Estações do Ano , Estudos Retrospectivos , Hospitalização
14.
J Mol Model ; 29(11): 345, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848622

RESUMO

CONTEXT: The study of CL-20 co-crystal has always been a focal point within the field of energetic material modification. In this study, we employed a combination of density functional theory and molecular dynamics simulations to investigate the properties of hexanitrohexaazaisowurtzitane (CL-20)/3-amino-5-nitro-1,2,4-triazole (ANTA) with different molar ratios ranging from 4:1 to 1:4. Additionally, EXPLO-5 software utilized to predict the detonation properties and products of pure CL-20, ANTA, and CL-20/ANTA systems. The results revealed that there was an interaction between CL-20 and ANTA molecules, which had the potential to form a co-crystal. The most likely molar ratio for co-crystal formation was 1:1, and the main driving forces for co-crystal formation were electrostatic force, dispersion force, and van der Waals force. The co-crystal explosive exhibited moderate sensitivity and excellent mechanical properties. Furthermore, the co-crystal detonation performance at a molar ratio of 1:1 was between that of CL-20 and ANTA, representing a new type of insensitive high-energy material. METHODS: The properties of CL-20/ANTA co-crystal were predicted by molecular dynamics (MD) method under Materials Studio software. For the whole MD simulations, set the temperature at 298 K, and the pressure was 0.0001 GPa. Conducted MD simulation under the NPT ensemble for a total simulation duration of 1 ns. The first 0.5 ns was used for thermodynamic equilibrium, and the last 0.5 ns was used for statistical calculation and analysis. Sampling was recorded every 10 fs during the calculation.

15.
Cell Commun Signal ; 21(1): 278, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37817162

RESUMO

BACKGROUND: Abnormal platelet activation is a key factor in the occurrence and development of thrombotic diseases. However, the physiological mechanisms that underlie platelet homeostasis remain unclear. Oleic acid, one of the most abundant lipids in the human diet, has potential antithrombotic effects. This study aimed to investigate the effects of oleic acid on platelet activation and thrombosis. METHODS: Platelet aggregation, ATP release, and fibrinogen spread were evaluated to determine the role of oleic acid in platelet activation. A ferric chloride-induced carotid injury model was used to establish the effect of oleic acid on thrombus formation in vivo. Western blotting analysis and transfection experiments were performed to determine the mechanisms involved in this process. RESULTS: Oleic acid inhibited platelet aggregation, granule release, and calcium mobilization. Furthermore, it inhibited the spread of platelets on fibrinogen. We also found that oleic acid delayed arterial thrombosis in mice, as demonstrated in a murine model of ferric chloride-induced carotid artery thrombosis. The molecular mechanism of its inhibition of platelet activity may be through the Syk-PLCγ2 and CaMKKß/AMPKα/VASP pathways. In addition, we demonstrated that the phosphorylation of AMPK at Ser496 was an important mechanism of platelet activation. CONCLUSIONS: Our study showed that oleic acid inhibits platelet activation and reduces thrombogenesis by inhibiting the phosphorylation of multiple signaling molecules, offering new insights into the research and development of antiplatelet drugs. Video Abstract.


Assuntos
Ácido Oleico , Trombose , Humanos , Camundongos , Animais , Ácido Oleico/farmacologia , Ácido Oleico/metabolismo , Ativação Plaquetária , Plaquetas , Trombose/metabolismo , Fosforilação , Colágeno/metabolismo , Fibrinogênio/metabolismo , Fibrinogênio/farmacologia
16.
MedComm (2020) ; 4(5): e392, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37808270

RESUMO

Tissue-type plasminogen activator (tPA) encoded by PLAT is a major mediator that promotes fibrinolysis and prevents thrombosis. Pathogenetic mutations in PLAT associated with venous thromboembolism have rarely been reported. Here, we report the first case of a homozygous point mutation c.1411T>C (p.Y471H) in PLAT leading to thromboembolic events and conduct related functional studies. The corresponding tPA mutant protein (tPA-Y471H) and wild-type tPA (tPA-WT) were synthesized in vitro, and mutant mice (PLATH/H mice) were constructed. The molecular docking and surface plasmon resonance results indicated that the mutation impeded the hydrogen-bonding interactions between the protease domain of tPA and the kringle 4 domain of plasminogen, and the binding affinity of tPA and plasminogen was significantly reduced with a difference of one order of magnitude. mRNA half-life assay showed that the half-life of tPA-Y471H was shortened. The inferior vena cava thrombosis model showed that the rate of venous thrombosis in PLATH/H mice was 80% compared with 53% in wild-type mice. Our data suggested a novel role for the protease domain of tPA in efficient plasminogen activation, and demonstrated that this tPA mutation could reduce the fibrinolysis function of the body and lead to an increased propensity for thrombosis.

17.
Environ Res ; 238(Pt 1): 117172, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729961

RESUMO

As alternatives for legacy brominated flame retardants, novel brominated flame retardants (NBFRs) have a wide array of applications in the electronic and electrical fields. The shift of recycling modes of electronic and electrical waste (e-waste) from informal recycling family workshop to formal recycling facilities might come with the change the chemical landscape emitted including NBFRs, however, little information is known about this topic. This study investigated the occurrence characteristics, distribution, and exposure profiles of eight common NBFRs and their derivatives in an e-waste recycling industrial park in central China and illustrated the differences in various functional zones in the recycling park. The highest level of ΣNBFRs in dust samples was found in e-waste storage area at median concentration of 27,400 ng/g, followed by e-waste dismantling workshops (23,300 ng/g), workshop outdoor area (7770 ng/g), and residential area outdoor (536 ng/g). In the e-waste dismantling associated dust samples, tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), tetrabromobisphenol A (TBBPA) and 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) were the predominant components. This paper presented the first evidence regarding the occurrence characteristic and distribution of tetrabromobisphenol S (TBBPS), tetrabromobisphenol A bismethyl ether (TBBPA-BME) and tetrabromobisphenol S bis(2,3-dibromopropyl ether) (TBBPS-BDBPE) in the e-waste associated dust samples. By comparing with previous studies performed in China, this paper also noticed the significant decrease of TBBPA concentrations in the dust probably due to the shift of e-wastes sources and recycling modes. We further assessed the risk of occupational workers exposure to NBFRs. The median EDI (estimated daily intake) value of ΣNBFRs among e-waste dismantling workers was 9.71 ng/kg BW/d with the maximum EDI value being 19.6 ng/kg BW/d, hundreds of times higher than those exposed by general population. The study raises great concern for the health risk of occupational exposure to NBFRs in the e-waste recycling industrial park.


Assuntos
Resíduo Eletrônico , Retardadores de Chama , Humanos , Poeira/análise , Retardadores de Chama/análise , Resíduo Eletrônico/análise , Reciclagem , Etil-Éteres , Éteres Difenil Halogenados/análise , Monitoramento Ambiental
18.
EClinicalMedicine ; 62: 102088, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37533415

RESUMO

Background: Two previous studies found alkaline phosphatase (ALP) levels were related with the development of venous thromboembolism (VTE) in hospitalised patients. VTE is a leading cause of death during pregnancy and postpartum. No prior study has investigated the associations of ALP levels and VTE postpartum, and the related mechanisms remain unclear. This study aimed to investigate the associations between ALP levels and VTE postpartum, and to reveal the potential mechanisms. Methods: In this retrospective cohort study, we included pregnant women who planned to deliver at the Department of Obstetrics and Gynecology in the three designated hospitals in a multicentre cohort of pregnant women in Wuhan, China, during two recruitment periods of January 1, 2018 to December 31, 2019, and May 14, 2020 to March 25, 2022. A total of 10,044 participants with serum ALP and whole blood hemoglobin measurements in late pregnancy (median, 37 (35, 39) weeks) were enrolled. The participants' incidences of VTE (deep venous thrombosis and/or pulmonary embolism) postpartum were confirmed from the medical records. Pregnant women with new-onset VTE postpartum (within 6 weeks after delivery) were confirmed as VTE cases. Findings: Approximately 0.8% (79/10,044) of the pregnant women were diagnosed with VTE postpartum. In the unadjusted model, pregnant women with the lowest quintile of serum ALP levels (≤116 U/L) in late pregnancy had higher risk of VTE postpartum compared with those with the highest quintile (≥199 U/L) (OR, 2.83 [1.32, 6.05]). After adjusting for covariates of demographic, life style, birth outcomes, and other liver enzymes, pregnant women with the lowest quintile of serum ALP levels (≤116 U/L) in late pregnancy had increased risk of VTE postpartum compared with those with the highest quintile (≥199 U/L) (OR, 2.48 [1.14, 5.40]). A one standard deviation decrease of ln-transformed ALP levels were associated with elevated risk of VTE postpartum (OR, 1.29 [1.02, 1.62]). Significant negative associations of ALP with VTE were found in the unadjusted and adjusted models. The negative associations between ALP and VTE remained consistent in sensitivity analyses among participants with non-GDM, single pregnancy, non-preeclampsia, non-postpartum hemorrhage, non-extremely/very preterm and cesarean delivery. Decreased serum ALP levels significantly (P < 0.05) related to decreased hemoglobin, which was significantly (P < 0.05) related to increased risk of VTE postpartum. Decreased hemoglobin significantly (P < 0.05) mediated 7.59% of ALP-associated VTE postpartum. Interpretation: This study suggested that low serum ALP levels in late pregnancy were associated with increased risk of VTE postpartum, and the ALP-associated VTE risk may be partially mediated by hemoglobin, suggesting that serum ALP in late pregnancy could be a promising biomarker for the prediction of VTE postpartum. Funding: The National Natural Science Foundation of China, and the Program for HUST Academic Frontier Youth Team.

19.
Environ Sci Technol ; 57(34): 12794-12805, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37579047

RESUMO

Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the relevant contamination profiles and impacts remain not well studied. This study investigated the occurrence of 28 OPEs and their metabolites (mOPEs) in rainfall runoffs and agricultural soils around one of the largest plastic recycling industrial parks in North China and identified novel organophosphorus compounds (NOPs) using high-resolution mass spectrometry-based nontarget analysis. Twenty and twenty-seven OPEs were detected in runoff water and soil samples, with total concentrations of 86.0-2491 ng/L and 2.53-199 ng/g dw, respectively. Thirteen NOPs were identified, of which eight were reported in the environment for the first time, including a chlorine-containing OPE, an organophosphorus heterocycle, a phosphite, three novel OPE metabolites, and two oligomers. Triphenylphosphine oxide and diphenylphosphinic acid occurred ubiquitously in runoffs and soils, with concentrations up to 390 ng/L and 40.2 ng/g dw, respectively. The downwind areas of the industrial park showed elevated levels of OPEs and NOPs. The contribution of hydroxylated mOPEs was higher in soils than in runoffs. These findings suggest that plastic recycling and reprocessing activities are significant sources of OPEs and NOPs and that biotransformation may further increase the ecological and human exposure risk.


Assuntos
Retardadores de Chama , Plastificantes , Humanos , Plásticos , Compostos Organofosforados/análise , Retardadores de Chama/análise , Solo , Organofosfatos/análise , China , Ésteres/análise , Monitoramento Ambiental
20.
J Hazard Mater ; 459: 132271, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37582303

RESUMO

E-waste dismantlers' occupational exposure to plasticizers, particularly non-phthalate (NPAE) plasticizers, is poorly understood. This study monitored 11 phthalates (PAEs) and 16 NPAEs in dust and hand wipe samples from Central China e-waste workplace and ordinary homes. Concentrations of plasticizers in dust from e-waste dismantling workshops (median: 217 µg/g) were significantly lower than that from ordinary homes (462 µg/g; p < 0.01), however, the trend was similar but not significant in hand wipes from these two scenarios (50.2 vs. 72.3 µg/m2; p = 0.139). PAEs were still the dominant plasticizers, which is, on average, 5.46 and 3.58-fold higher than NPAEs. In all samples, di-(2ethylhexyl) phthalate (65.4%) and tri-octyl trimellitate (44.9%) were the most common PAE and NPAE plasticizers. Increasing dust concentrations of di-iso-nonyl ester 1,2-cyclohexane dicarboxylic acid, citrates and sebacates were significantly associated with their levels in worker's hand wipe, by contrast, this trend was not found in general population. Dust ingestion was the main channel, followed by hand-to-mouth contact, all participants' daily plasticizer intakes (median: 154 ng/kg bw/day) are within safety limits. Our work highlights knowledge gaps about co-exposure to PAEs and NPAEs by multiple pathways in occupational e-waste workers, which could provide baseline data in the future.


Assuntos
Exposição Ocupacional , Ácidos Ftálicos , Humanos , Exposição Ambiental/análise , Plastificantes/análise , Poeira , Ácidos Ftálicos/análise
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