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1.
Sci Total Environ ; 932: 172876, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38692326

RESUMO

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

2.
J Hazard Mater ; 470: 134298, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626679

RESUMO

4-methylbenzylidene camphor (4-MBC) and micro/nanoplastics (MNPs) are common in personal care and cosmetic products (PCCPs) and consumer goods; however, they have become pervasive environmental contaminants. MNPs serve as carriers of 4-MBC in both PCCPs and the environment. Our previous study demonstrated that 4-MBC induces estrogenic effects in zebrafish larvae. However, knowledge gaps remain regarding the sex- and tissue-specific accumulation and potential toxicities of chronic coexposure to 4-MBC and MNPs. Herein, adult zebrafish were exposed to environmentally realistic concentrations of 4-MBC (0, 0.4832, and 4832 µg/L), with or without polystyrene nanoplastics (PS-NPs; 50 nm, 1.0 mg/L) for 21 days. Sex-specific accumulation was observed, with higher concentrations in female brains, while males exhibited comparable accumulation in the liver, testes, and brain. Coexposure to PS-NPs intensified the 4-MBC burden in all tested tissues. Dual-omics analysis (transcriptomics and proteomics) revealed dysfunctions in neuronal differentiation, death, and reproduction. 4-MBC-co-PS-NP exposure disrupted the brain histopathology more severely than exposure to 4-MBC alone, inducing sex-specific neurotoxicity and reproductive disruptions. Female zebrafish exhibited autism spectrum disorder-like behavior and disruption of vitellogenesis and oocyte maturation, while male zebrafish showed Parkinson's-like behavior and spermatogenesis disruption. Our findings highlight that PS-NPs enhance tissue accumulation of 4-MBC, leading to sex-specific impairments in the nervous and reproductive systems of zebrafish.


Assuntos
Cânfora , Cânfora/análogos & derivados , Peixe-Zebra , Animais , Masculino , Feminino , Cânfora/toxicidade , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Poliestirenos/toxicidade , Nanopartículas/toxicidade , Reprodução/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Compostos Benzidrílicos/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo
3.
Environ Health Perspect ; 132(2): 27011, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381479

RESUMO

BACKGROUND: Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear. OBJECTIVES: This study aimed to investigate the influence of MNPs on HMS-induced estrogenic effects and elucidate the underlying mechanisms in vitro and in vivo. METHODS: We assessed the impact of polystyrene nanospheres (PNSs; 50 nm, 1.0mg/L) on HMS-induced MCF-7 cell proliferation (HMS: 0.01-1µM, equivalent to 2.62-262µg/L) using the E-SCREEN assay and explored potential mechanisms through transcriptomics. Adult zebrafish were exposed to HMS (0.0262-262µg/L) with or without PNSs (50 nm, 1.0mg/L) for 21 d. EDEs were evaluated through gonadal histopathology, fertility tests, steroid hormone synthesis, and gene expression changes in the hypothalamus-pituitary-gonad-liver (HPGL) axis. RESULTS: Coexposure of HMS and PNSs resulted in higher expression of estrogen receptor α (ESR1) and the mRNAs of target genes (pS2, AREG, and PGR), a greater estrogen-responsive element transactivation activity, and synergistic stimulation on MCF-7 cell proliferation. Knockdown of serum and glucocorticoid-regulated kinase 1 (SGK1) rescued the MCF-7 cell proliferation induced by PNSs alone or in combination with HMS. In zebrafish, coexposure showed higher expression of SGK1 and promoted ovary development but inhibited spermatogenesis. In addition, coexposure led to lower egg hatchability, higher embryonic mortality, and greater larval malformation. Coexposure also modulated steroid hormone synthesis genes (cyp17a2, hsd17[Formula: see text]1, esr2b, vtg1, and vtg2), and resulted in higher 17ß-estradiol (E2) release in females. Conversely, males showed lower testosterone, E2, and gene expressions of cyp11a1, cyp11a2, cyp17a1, cyp17a2, and hsd17[Formula: see text]1. DISCUSSION: PNS exposure exacerbated HMS-induced estrogenic effects via SGK1 up-regulation in MCF-7 cells and disrupting the HPGL axis in zebrafish, with gender-specific patterns. This offers new mechanistic insights and health implications of MNP and contaminant coexposure. https://doi.org/10.1289/EHP13696.


Assuntos
Nanosferas , Adulto , Feminino , Humanos , Masculino , Animais , Peixe-Zebra , Células MCF-7 , Poliestirenos/toxicidade , Estrogênios , Glucocorticoides , Esteroides
4.
Environ Pollut ; 335: 122260, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37506809

RESUMO

4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 µg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (erα) mRNA, and an interaction between 4-MBC and ERα suggested ERα's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.


Assuntos
Estrogênios , Peixe-Zebra , Animais , Estrogênios/farmacologia , Peixe-Zebra/metabolismo , Receptor alfa de Estrogênio/metabolismo , Acetilcolinesterase/metabolismo , Protetores Solares/toxicidade , Gônadas/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Cânfora/toxicidade , Fígado/metabolismo , Encéfalo/metabolismo
5.
J Asian Nat Prod Res ; 24(10): 935-944, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36000737

RESUMO

A pair of stilbenes with γ-lactam unit [(+)-1 and (-)-1], a new phenolic glucoside (2), and a new isoflavone glucoside (3), together with two known compounds (4-5) were isolated from the rhizomes of Belamcanda chinensis. The chemical structures of the undescribed compounds were elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 4, and 5 (10 µM) exhibited anti-inflammatory activities with inhibition rates of 30.46%, 60.34%, and 37.91%, respectively, against the NF-κB signaling pathway.


Assuntos
Iridaceae , Gênero Iris , Estilbenos , Rizoma/química , Iridaceae/química , Estilbenos/farmacologia , Estrutura Molecular , Fenóis/farmacologia , Fenóis/química , Glucosídeos/farmacologia
6.
Phytochemistry ; 203: 113370, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35977602

RESUMO

Four undescribed flavonoid glucosides (iridins B-C, tectoridin A and ampelopsinin A); one undescribed phenolic glucoside (diplostephioside B); one undescribed phenolic compound (phenanthrenetriol A); and seventeen known compounds were isolated from the rhizomes of Iris domestica. The chemical structures of the undescribed compounds were established by spectroscopic/spectrometric data interpretation using HRESIMS, NMR, and ECD. Tectoridin A, nigricin A and naringenin exhibited anti-inflammatory activities with inhibition rates of 53.71%, 57.68% and 88.71%, respectively, against the NF-κB signaling pathway at a concentration of 10 µM. 4'-O-methylnyasol (10 µM) exhibited 84.91% antiproliferative activity against the K562 human leukemia cell line with an IC50 value of 4.20 µM.


Assuntos
Antineoplásicos , Gênero Iris , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Flavonoides/análise , Glucosídeos/química , Humanos , Gênero Iris/química , Estrutura Molecular , NF-kappa B , Fenóis , Rizoma/química
7.
PLoS One ; 17(2): e0262942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35171916

RESUMO

This study was designed to explore the therapeutics and the mechanisms of a patented and marked gastric acid and intestine juice-resistant probiotics Bifidobacterium lactis BL-99 (B. lactis BL-99) on the intestinal inflammation and functions in the zebrafish models. After feeding for 6 hours, B. lactis BL-99 was fully retained in the larval zebrafish intestinal tract and stayed for over 24 hours. B. lactis BL-99 promoted the intestinal motility and effectively alleviated aluminum sulfate-induced larval zebrafish constipation (p < 0.01). Irregular high glucose diet induced adult zebrafish intestinal functional and metabolic disorders. After fed with B. lactis BL-99, IL-1ß gene expression was significantly down-regulated, and IL-10 and IL-12 gene levels were markedly up-regulated in this model (p < 0.05). The intestinal lipase activity was elevated in the adult zebrafish intestinal functional disorder model after B. lactis BL-99 treatment (p < 0.05), but tryptase content had no statistical changes (p > 0.05). B. lactis BL-99 improved the histopathology of the adult zebrafish intestinal inflammation, increased the goblet cell numbers, and up-and-down metabolites were markedly recovered after treatment of B. lactis BL-99 (p < 0.05). These results suggest that B. lactis BL-99 could relieve intestinal inflammation and promote intestinal functions, at least in part, through modulating intestinal and microbial metabolism to maintain intestinal health.


Assuntos
Bifidobacterium/fisiologia , Inflamação/terapia , Intestinos/metabolismo , Probióticos/uso terapêutico , Compostos de Alúmen/toxicidade , Animais , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/patologia , Constipação Intestinal/terapia , Análise Discriminante , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Glucose/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Intestinos/microbiologia , Intestinos/patologia , Larva/efeitos dos fármacos , Larva/metabolismo , Probióticos/farmacologia , Regulação para Cima/efeitos dos fármacos , Peixe-Zebra/crescimento & desenvolvimento
8.
Toxicol Lett ; 354: 1-13, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718095

RESUMO

Aurantio-obtusin (AO) is a major anthraquinone (AQ) compound derived from Cassiae semen (CS). Although pharmacological studies have shown that the CS extracts can serve as effective agents in preclinical and clinical practice, AQ-induced hepatotoxicity in humans has attracted widespread attention. To explore whether AO induces hepatotoxicity and its underlying mechanisms, we exposed larval zebrafish and mice to AO. We found that AO delayed yolk sac absorption, and increased liver area and inflammation in the larval zebrafish. This inflammation was manifested as an increase in liver neutrophils and the up-regulated mRNA expression of interleukin-6 (Il-6) and tumor necrosis factor-α (Tnf-α) in the larval zebrafish. Furthermore, a pharmacokinetics study showed that AO was quickly absorbed into the blood and rapidly metabolized in the mice. Of note, AO induced hepatotoxicity in a gender-dependent manner, characterized by liver dysfunction, increased hepatocyte necrosis with inflammatory infiltration, and up-regulated mRNAs of Il-6, Tnf-α and monocyte chemotactic protein 1(Mcp1) in the female mice after 28-day oral administration. It also highlighted that AO triggered NOD-like receptor protein (NLRP) signaling in the female mice, as evidenced by the increased NLRP3, Caspase-1, pro-IL-1ß, IL-1ß and IL-18. Finally, we found that AO led to a significant increase in potassium calcium-activated channel, subfamily N, member 4 (KCNN4) and reactive oxygen species (ROS) levels, along with decreased nuclear factor kappa B p65 (NF-κB p65), in the female mouse livers. In conclusion, AO induced hepatotoxicity by activating NLRP3 inflammasome signaling, at least in part, through increased KCNN4 and ROS production, and NF-κB inhibition.


Assuntos
Antraquinonas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Peixe-Zebra/metabolismo , Animais , Cassia/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Humanos , Larva/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos
9.
Front Cell Dev Biol ; 9: 721130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595173

RESUMO

The zebrafish as an alternative animal model for developmental toxicity testing has been extensively investigated, but its assay protocol was not harmonized yet. This study has validated and optimized the zebrafish developmental toxicity assay previously reported by multiple inter-laboratory studies in the United States and Europe. In this study, using this classical protocol, of 31 ICH-positive compounds, 23 compounds (74.2%) were teratogenic in zebrafish, five had false-negative results, and three were neither teratogenic nor non-teratogenic according to the protocol standard; of 14 ICH-negative compounds, 12 compounds (85.7%) were non-teratogenic in zebrafish and two had false-positive results. After we added an additional TI value in the zebrafish treated with testing compounds at 2 dpf along with the original 5 dpf, proposed a new category as the uncategorized compounds for those TI values smaller than the cutoff both at 2 dpf and 5 dpf but inducing toxic phenotypes, refined the testing concentration ranges, and optimized the TI cut-off value from ≥ 10 to ≥ 3 for compounds with refined testing concentrations, this optimized zebrafish developmental assay reached 90.3% sensitivity (28/31 positive compounds were teratogenic in zebrafish) and 88.9% (40/45) overall predictability. Our results from this study strongly support the use of zebrafish as an alternative in vivo method for screening and assessing the teratogenicity of candidate drugs for regulatory acceptance.

10.
Molecules ; 26(14)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34299477

RESUMO

As a traditional Chinese medicine, Patrinia scabiosifolia Link has been used to treat various inflammatory-related diseases, and recent studies have shown that it possesses potent anti-inflammatory activity. Therefore, phytochemical investigation on whole plants of P. scabiosifolia were carried out, which led to the isolation of two new iridoid glucosides, patriniscabiosides A (1) and B (2), together with six known compounds (3-8). The structural elucidation of all compounds was performed by HRESIMS and extensive spectroscopic analyses including IR, 1D, 2D NMR, and electronic circular dichroism (ECD). All the isolated compounds were tested for their anti-inflammatory activity using the NF-κB-Dependent Reporter Gene Expression Assay, and compound 3 displayed anti-inflammatory activity through the inhibition of the NF-κB pathway, with an inhibitory rate of 73.44% at a concentration of 10 µM.


Assuntos
Anti-Inflamatórios/farmacologia , Glucosídeos Iridoides/farmacologia , NF-kappa B/antagonistas & inibidores , Patrinia/química , Anti-Inflamatórios/química , Células HEK293 , Humanos , Estrutura Molecular
11.
Part Fibre Toxicol ; 18(1): 20, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098985

RESUMO

BACKGROUND: Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current "microplastic exposure" is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected. RESULTS: We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure. CONCLUSIONS: There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.


Assuntos
Microplásticos , Poliestirenos , Animais , Apoptose , Células Epiteliais , Camundongos , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Espécies Reativas de Oxigênio , Distribuição Tecidual
12.
Zebrafish ; 17(6): 382-393, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33232637

RESUMO

This study was aimed to assess effects of three strains of probiotics Lactobacillus acidophilus NCFM, Lactobacillus rhamnosus HN001, and Bifidobacterium animalis subsp. lactis Bi-07 on the intestinal motility and inflammation in the zebrafish models. The intestinal motility model was established using 5 days postfertilization (dpf) zebrafish administered with a fluorescent dye Nile red at 10 ng/mL for 16 h, followed by probiotics treatment for 24 h and the intestinal motility was inversely proportional to the intestinal fluorescence intensity that was quantitatively measured by image analysis. The intestinal inflammation was induced by treating 3 dpf neutrophil fluorescent zebrafish with 0.0125% of trinitrobenzenesulfonic acid for 48 h. Probiotics were administered at low, moderate, and high concentrations determined based on maximum tolerable concentration through soaking. All three strains of probiotics promoted intestinal movement, of which B. animalis subsp. lactis Bi-07 was most potent at lower concentrations. L. rhamnosus HN001 and B. animalis subsp. lactis Bi-07 had the therapeutic effects on the intestinal inflammation and the inflammation-associated mucosal damage recovery. The anti-inflammatory mechanisms of L. rhamnosus HN001 was related to both reduce inflammatory factor interleukin-6 (IL-6) and restored tissue repair factor transforming growth factor-ß-1 (TGFß-1); whereas B. animalis subsp. lactis Bi-07 was probably only associated with TGFß-1 elevation. Using larval zebrafish models for probiotics screening and assessment would speed up product research and development and improve products' efficacy and quality.


Assuntos
Bifidobacterium animalis/química , Motilidade Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Lacticaseibacillus rhamnosus/química , Lactobacillus acidophilus/química , Probióticos/farmacologia , Peixe-Zebra , Animais , Inflamação/fisiopatologia
13.
Eur J Pharmacol ; 889: 173292, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32668288

RESUMO

Conventional mammalian ischemic stroke models for drug screening are technically challenging, laborious and time-consuming. In this study, using Ponatinib as an inducer, we developed and characterized a zebrafish ischemic stroke model. This zebrafish ischemic stroke had the cerebral vascular endothelial injury, thrombosis, reduced blood flow, inflammation and apoptosis as well as the reduced motility. The zebrafish ischemic stroke model was validated with 6 known human therapeutic drugs of ischemic stroke (Aspirin, Clopidogrel, Naoxintong capsules, Edaravone, Xingnaojing injection, Shuxuening injection). The mRNA levels of the neovascularization-related gene (vegfaa) and vascular endothelial growth factor receptor gene (VEGFR), neurodevelopment related genes (mbp and α1-tubulin), brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) were significantly downregulated; whereas apoptosis-related genes (caspase-3, caspase-7, caspase-9 and bax/bcl-2), and inflammatory factor genes (IL-1ß, IL-6, IL-10, TNF-α and NF-κB) were remarkably upregulated in the model. These results suggest that the pathophysiology of Ponatinib-induced zebrafish ischemic stroke is similar to that of human ischemic stroke patients and this whole animal model could be used to study the complex cellular and molecular pathogenesis of ischemic stroke and to rapidly identify therapeutic agents.


Assuntos
Antineoplásicos/toxicidade , Isquemia Encefálica/induzido quimicamente , Modelos Animais de Doenças , Imidazóis/toxicidade , AVC Isquêmico/induzido quimicamente , Larva/efeitos dos fármacos , Piridazinas/toxicidade , Animais , Animais Geneticamente Modificados , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Peixe-Zebra
14.
PLoS One ; 15(4): e0232020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324798

RESUMO

OBJECTIVE: To evaluate systematically the quality of the cohort studies on rheumatic diseases in China. METHODS: Relevant databases were searched to find cohort studies on rheumatic diseases in China, and the basic information included in the literature was extracted and analyzed. Chinese and English literature were then compared with regard to methodological quality, according to the Newcastle-Ottawa Scale (NOS). RESULTS: In total, we included 46 cohort studies, with 19 studies published in English and 27 studies published in Chinese. With regard to the basic characteristics of the literature, 78.26% of the studies were published in the past four years; 16 studies were associated with hyperuricemia, followed by eight studies involving systemic lupus erythematosus. The sample size of the studies in Chinese was lower than that in English studies (P< 0.05). The English literature was superior to the Chinese literature in terms of informed consent, ethical review and selection of statistical analysis methods. The methodology quality of the 46 included studies showed that the English and Chinese NOS scores were 5.59 ± 1.25 and 6.06 ± 1.11, respectively, and the difference was significant (P< 0.01). The "representativeness of the exposed group", "demonstration that outcome of interest was not present at start of study", and the "adequacy of follow up of cohorts" scores were relatively low in Chinese and English studies. The score for "was follow-up long enough for outcomes to occur" item in English was higher than that in the Chinese studies; however, the "study controls for the most important factor" score for Chinese papers was better than that for the English papers. CONCLUSION: The Chinese rheumatic disease cohort studies started late, with a small sample size and fewer types of rheumatism. The quality of Chinese studies was better than English studies, and all reports were insufficient. In particular, "selecting exposed groups", "controlling the outcomes before study implementation" and "adequacy of follow-up" needed improvement.


Assuntos
Projetos de Pesquisa/normas , Doenças Reumáticas , China , Estudos de Coortes , Humanos , Controle de Qualidade , Tamanho da Amostra
15.
Neurotoxicology ; 79: 11-19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32247646

RESUMO

Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is an extensively used carbamate insecticide. Its developmental neurotoxicity and the underlying mechanisms have not been well investigated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 6 hpf (hours post fertilization, hpf) to 120 hpf. BPMC induced developmental toxicity with reduced motility in larval zebrafish. The spinal cord neutrophil infiltration, increased ROS production, caspase 3 and 9 activation, central nerve and peripheral motor neuron damage, axon and myelin degeneration were observed in zebrafish treated with BPMC generally in a dose-dependent manner. The expression of eight marker genes for nervous system function or development, namely, a1-tubulin, shha, elavl3, gap43, syn2a, gfap, mbp and manf, was significantly downregulated following BPMC exposure. AChE activity reduction and ache gene expression suppression was also found significantly in BPMC-treated zebrafish. These results indicate that BPMC is highly toxic to zebrafish and that BPMC induces zebrafish developmental neurotoxicity through pathways involved in inflammation, oxidative stress, degeneration and apoptosis.


Assuntos
Carbamatos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Inseticidas/toxicidade , Sistema Nervoso/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Embrião não Mamífero/patologia , Regulação da Expressão Gênica no Desenvolvimento , Mediadores da Inflamação/metabolismo , Locomoção/efeitos dos fármacos , Degeneração Neural , Sistema Nervoso/embriologia , Sistema Nervoso/metabolismo , Sistema Nervoso/patologia , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
16.
J Pharmacol Toxicol Methods ; 102: 106681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32087362

RESUMO

INTRODUCTION: This study was aimed to assess uric acid (UA)-lowering effect and its possible mechanisms of a natural complex product Yaocha in a live zebrafish model. METHODS: The zebrafish high UA model was established by feeding 5 dpf zebrafish with both an uricase inhibitor potassium oxonate at 10 mM and an UA synthesis precursor xanthine sodium at 0.5 mM for 24 h. Yaocha was administered to the high UA zebrafish through soaking at 3 various concentrations, with allopurinol as a positive control. UA level, xanthine oxidase (XOD) activity, and mRNA expression of hypoxanthine guanine-phosphoribosyltransferases transferase (HPRT1) and organic anion transporter 1 (OAT1) were measured. RESULTS: Yaocha effectively reduced UA level and inhibited xanthine oxidase (XO) activity in the high UA zebrafish. Yaocha could be a potential therapeutics for hyperuricemia through up-regulating HPRT1 and OAT1 gene expression and suppressing XO activity. DISCUSSION: These results suggested that Yaocha hold a potential for high UA prevention and therapy, possibly through inhibiting UA production and promoting urate secretion and purine conversion.


Assuntos
Produtos Biológicos/farmacologia , Hiperuricemia/tratamento farmacológico , Ácido Úrico/sangue , Animais , Aspalathus/química , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Dipeptídeos/administração & dosagem , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Hipoxantina Fosforribosiltransferase/genética , Proteína 1 Transportadora de Ânions Orgânicos/genética , Theaceae/química , Peixe-Zebra
17.
J Clin Lab Anal ; 33(8): e22957, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31218740

RESUMO

BACKGROUND: Low concentration C-reactive protein (CRP) has favorable prognostic significance in patients with cardiovascular risks. METHODS: We compared the wr-CRP method with the hs-CRP method both on Roche Cobas c702 analyzer for the determination of low CRP concentration (<20 mg/L) including 200 patients treated in Cardiology Department in Beijing Tsinghua Changgung Hospital (Beijing, China) from December 2018 to March 2019. RESULTS: The two methods were highly correlated (Spearman's rho = 0.995). Deming regression was used to fit the regression analysis model, giving a slope of 1.058 with an intercept of 0.008. The median method difference (wr-CRP - hr-CRP) was 0.120 mg/L (95% CI, 0.086-0.200 mg/L), and the median percent differences were 7.34% (95% CI, 4.27%-8.47%). The percent bias between both methods at the given cutoff CRP values of 1, 3, and 10 mg/L evaluated by Deming regression was 6.60%, 6.07%, and 5.88%, respectively, all of which were less than the acceptable standard (12.50%). The percentage of sample results concordant by both methods for the risk stratification was 96.0% (kappa = 0.937, P < 0.001). CONCLUSIONS: Roche wr-CRP and hs-CRP assays are highly concordant in determining low concentration CRP. Wr-CRP may be used as an alternative to hs-CRP assay on Roche Cobas c702 analyzer to assess the cardiovascular risk, considering its convenience and lower costs.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Testes Diagnósticos de Rotina/métodos , Programas de Rastreamento/métodos , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Testes Diagnósticos de Rotina/classificação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(6): 543-547, 2018 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31032590

RESUMO

OBJECTIVE: Through the establishment of abortion model caused by embryo implantation difficulties, exploring the role of Yun Kang oral liquid in protecting embryos. METHODS: The pregnant rats were divided into 6 groups:normal control group (NC), model group (MG), dydrogesterone group (DT), and three dose groups of low, medium and high levels of Yun Kang oral liquid (YK-L, YK-M, YK-H), 11 in each group.From the first day of pregnancy, daily intragastric administration, the dose of DT group was 3.02 mg/kg, and the doses of Yun Kang oral liquid were 4, 6, and 9 ml/kg, respectively.The rats in NC and MG were treated with an equal volume of purified water for 10 days.On the third day of pregnancy, except for the NC group, the other groups were injected with mifepristone subcutaneously at the back of the neck at a dose of 5 mg/kg to cause an embryo implantation barrier model.On the 10th day of pregnancy, blood was collected from the abdominal aorta in each group.Serum follicle stimulating hormone (FSH), interferon-γ (IFN-γ) and interleukin (IL-4) were measured by enzyme-linked immunosorbent assay.The number of embryo implantation was observed in the uterus, and the pathological changes of the uterus were observed by HE staining. RESULTS: Compared with the NC group, the number of embryo implantation and the serum levels of FSH and IL-4 in the MG group were decreased significantly (P< 0.05, 0.01), and pathological changes such as uterine glandular epithelial hyperplasia and inflammatory cell infiltration in the glandular cavity were observed.Compared with MG group, the number of embryo implantation and serum FSH and IL-4 levels of rats in YK-M and YK-H groups were increased significantly (P<0.05, 0.01).The pathological changes such as uterine glandular epithelial hyperplasia and inflammatory cell infiltration in the gland were also improved.There was no significant difference in serum IFN-γ levels between the groups. CONCLUSIONS: Yun Kang oral liquid may improve the endometrial pathological changes and increase the number of embryo implantation by increasing the levels of serum sex hormone FSH and immune cytokine IL-4 in embryo implantation impediment rats.


Assuntos
Implantação do Embrião , Útero , Animais , Citocinas , Feminino , Interferon gama , Gravidez , Ratos
19.
Int J Clin Exp Med ; 8(7): 10986-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26379894

RESUMO

Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L-threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D-glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What's more, liver injury of alcohol extraction group was more serious than group of water extraction.

20.
J Nanosci Nanotechnol ; 13(3): 1927-30, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23755622

RESUMO

A kind of novel magnetic carbon nanotube composite was prepared and designed for wastewater treatment. Multi-walled carbon nanotubes were decorated with magnetic iron oxide nanoparticles, with an uniform distribution on the nanotube surface. The functionalized carbon nanotubes exhibit superparamagnetic behavior and can be easily and rapidly separated from the dispersion via a magnetic process. The carbon nanotube-iron oxide composites might serve as adsorbent for contaminant adsorption in water, especially for copper ammonia complex removal. The adsorption of copper ammonia complex to carbon nanotube-iron oxide composites is time dependent, and they can be quickly and efficiently removed together through a magnetic separation process. This novel magnetic composites might serve as an efficient and proper adsorbent in wastewater treatment applications.

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