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1.
Ecotoxicol Environ Saf ; 220: 112367, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34052758

RESUMO

Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 µmol/L ZEA and either 50 µmol/L AICAR or 5 µmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Estrogênios não Esteroides/toxicidade , Ácido Láctico/metabolismo , Células de Sertoli/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Metabolismo Energético/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Glicólise/genética , Masculino , Ácido Pirúvico/metabolismo , Ratos , Células de Sertoli/metabolismo
2.
Nanotechnology ; 32(33)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-33971629

RESUMO

The unbalanced charge transport is always a key influencing factor on the device performance of quantum dot light-emitting diodes (QLEDs), particularly for the blue QLEDs due to their large optical band gap. Here, a method of electron transport layer (ETL) doping was developed to regulate the energy levels and the carrier mobility of the ETL, which resulted in more balanced charge injection, transport and recombination in the blue emitting CdZnS/ZnS core/shell QLEDs. Consequently, an enhanced performance of blue QLEDs was achieved by modulating the charge balance through ETL doping. The maximum external quantum efficiency and luminance was dramatically increased from 2.2% to 7.3% and from 3786 cd m-2to 9108 cd m-2, respectively. The results illustrate that charge transport layer doping is a simple and effective strategy to regulate the charge injection barrier and carrier mobility of QLEDs.

3.
Tob Induc Dis ; 19: 10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584165

RESUMO

INTRODUCTION: There are few reports on the beliefs about thirdhand smoke in Chinese families with primary school children. This study aims to understand the beliefs about thirdhand smoke among parents or grandparents of primary school children in Shanghai and to provide an evidence base to incorporate thirdhand smoke preventative action into tobacco control interventions. METHODS: We performed a cross-sectional survey among parents and grandparents of children aged 6-13 years in the Changjiang Road Primary School and recruited 843 participants to make assessments on the 'beliefs about thirdhand smoke' (BATHS) scale. Sociodemographic details including age, gender, marital status, education level, personal income and type of home ownership (new house, secondhand house with or without redecoration) and health status of children (whether they suffered from respiratory diseases or not) were investigated. Scale assessment, univariate and multivariate analyses to explore the factors influencing the BATHS scale and subscale scores, were performed using SPSS version 22.0. RESULTS: Participants who were aged >65 years were more likely to get lower scores on the BATHS scale (OR=0.476; 95% CI: 0.311-0.728, p=0.001). Undergraduates (OR=1.190; 95% CI: 1.020-1.388, p=0.027) and graduates (OR=1.4490; 95% CI: 1.102-1.906, p=0.008) obtained higher scores. Moreover, the scores of residents living in a secondhand house with redecoration (OR=0.882; 95% CI: 0.782-0.995, p=0.041) and without redecoration (OR=0.801; 95% CI: 0.698-0.919, p=0.002) were lower compared with those of new-house owners. The scores for participants whose children suffered from respiratory diseases in the past six months (OR=1.104; 95% CI: 1.003-1.216, p=0.043) were higher than those whose children had no respiratory diseases. CONCLUSIONS: This study shows that younger people, females, those with higher incomes, and higher education levels, were more likely to believe the thirdhand smoke impacts on health and its persistence in the environment. Our findings can guide targeted actions for smoke-free home interventions.

4.
Sci Total Environ ; 765: 142740, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33071125

RESUMO

Mechanisms for hematotoxicity and health effects from exposure to low doses of benzene (BZ) remain to be identified. To address the information gap, our investigation was focused onto using appropriate populations and cell cultures to investigate novel BZ-induced effects such as disruption of DNA repair capacity (DRC). From our study, abnormal miRNAs were identified and validated using lymphocytes from 56 BZ-poisoned workers and 53 controls. In addition, 173 current BZ-exposed workers and 58 controls were investigated for key miRNA expression using RT-PCR and for cellular DRC using a challenge assay. Subsequently, the observed activities in lymphocytes were verified using human HL-60 (p53 null) and TK6 (p53 wild-type) cells via 1,4-benzoquinone (1,4-BQ) treatment and miR-222 interferences. The targeting of MDM2 by miR-222 was validated using a luciferase reporter. Our results indicate induction of genotoxicity in lymphocytes from workers with low exposure doses to BZ. In addition, miR-222 expression was up-regulated among both BZ-poisoned and BZ-exposed workers together with inverse association with DRC. Our in vitro validation studies using both cell lines indicate that 1,4-BQ exposure increased expression of miR-222 and Comet tail length but decreased DRC. Loss of miR-222 reduced DNA damage, but induced S-phase arrest and apoptosis. However, silencing of MDM2 failed to activate p53 in TK6 cells. In conclusion, our in vivo observations were confirmed by in vitro studies showing that BZ/1,4-BQ exposures caused genotoxicity and high expression of miR-222 which obstructed expression of the MDM2-p53 axis that led to failed activation of p53, abnormal DRC and serious biological consequences.


Assuntos
Benzeno , MicroRNAs , Apoptose , Benzeno/toxicidade , Dano ao DNA , Reparo do DNA , Humanos , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
5.
J Asian Nat Prod Res ; 23(2): 138-149, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009450

RESUMO

Three series of sulfonate derivatives of paeonol were synthesized and screened in vitro for their anti-oomycete activity against P. capsici, respectively. Among all the compounds, 4m displayed the best promising and pronounced anti-oomycete activity against P. capsici than zoxamide, with the EC50 values of 24.51 and 26.87 mg/L, respectively. The results show that acetyl and 4-OCH3 are two necessary groups. The existence of these two sites is closely related to the anti-oomycete activity. Relatively speaking, hydroxyl group is well tolerated, and the results showed that after modification of hydroxyl group with sulfonyl, the anti-oomycete activity was significantly increased. [Formula: see text].


Assuntos
Acetofenonas , Acetofenonas/farmacologia , Estrutura Molecular
6.
Int J Pharm ; 592: 120098, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33220381

RESUMO

Drug toxicity and insufficient drug dosing place a limit on the effect of chemotherapy. Optimal efficacy is achieved by exposing tumor cells to the maximum tolerated dose of a chemotherapeutic drug. In this study, we developed a strategy (graphic summary) for enhancing the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to achieve actively guided tumor targeting of the photothermal therapeutic agent indocyanine green (ICG) and the chemotherapeutic drug 2-methoxyestradiol (2-ME), which were loaded into thermosensitive liposomes (TSLs) with surface-grafted tumor-targeting peptide cRGDyk (cRGDyk-2-ME@ICG-TSLs). In vitro studies demonstrated that cRGDyk-2-ME@ICG-TSLs effectively induced drug accumulation and cytotoxicity in NIR laser-irradiated B16-F10 melanoma cells using dual targeting based on the cRGDyk peptide and temperature sensitivity. An in vivo study showed that 24 h after intravenously injecting cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, the dual-mode NIR fluorescence/photoacoustic imaging could accurately identify tumors and normal tissues. In addition, the combination of cRGDyk-2-ME@ICG-TSLs and NIR radiation suppressed tumor growth in tumor-bearing nude mice and was associated with a low risk of side effects on normal organs. Our results indicate that TSLs are a suitable drug delivery system for diagnostic and chemotherapeutic agents guided by dual-mode imaging.


Assuntos
Verde de Indocianina , Fototerapia , 2-Metoxiestradiol , Animais , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Medicina de Precisão , Nanomedicina Teranóstica
7.
J Hazard Mater ; 401: 123390, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32659584

RESUMO

Monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), phthalate metabolites (mPAEs), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine of school children aged 8-11 years from Shenzhen, China were measured in order to investigate oxidative stress damage from co-exposure to PAHs and PAEs. The concentrations of OH-PAHs and mPAEs in urine were 0.36-36.5 (median: 3.86) and 9.48-1609 (median: 240) ng/mL respectively. Gender and age did not influence urinary concentrations of ΣOH-PAHs and ΣmPAEs, but geographical variations (i.e., urban versus suburban) were observed. Levels of 8-OHdG were positively correlated with urinary OH-PAHs and mPAEs, with correlation coefficients (r) varying between 0.160 and 0.365 (p < 0.05). OH-PAHs made a greater contribution to oxidative DNA damage than mPAEs when these two types of pollutants were present at the same concentrations. Human health risks were assessed using the hazard quotient and the hazard index for the cumulative risk of a complex of chemicals. The results demonstrated that risks from PAHs could be neglected, but that 29.5 % of school children may be subject to obvious health risks from PAEs, especially diethylhexyl phthalate.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Biomarcadores/metabolismo , Criança , China , Humanos , Estresse Oxidativo , Ácidos Ftálicos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Instituições Acadêmicas
8.
Tob Induc Dis ; 18: 76, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32994762

RESUMO

INTRODUCTION: The use of electronic cigarettes (e-cigarettes) in adults is increasing globally, and similar trends may be observed in the young population. Our objective was to estimate the awareness and use of e-cigarettes among the students from two comprehensive universities in Shanghai, China, and to identify the factors that may influence their decision to use e-cigarettes and their possible adverse effects. METHODS: An online cross-sectional survey was conducted among the students of Shanghai Jiao Tong University and Fudan University. A total of 869 students (412 males and 457 females), mean age 21.09 years (SD=2.44), were recruited in 2018. Multivariate binary logistic regression analyses were performed to explore the associations between ever e-cigarette use and influencing factors. RESULTS: Of the responding students, 88.4% were aware of e-cigarettes, 4.6% had used e-cigarettes at least once in their lifetime, and 1.7% were current e-cigarettes users. Males and smokers were more likely to use e-cigarettes (ever used e-cigarettes even once) than females (OR=3.51; 95% CI: 1.69-7.27; p=0.001) and non-smokers (OR=28.58; 95% CI: 14.03-58.20; p<0.001). University students were easily motivated to use e-cigarettes when their peers also used them, and the risk ratio was 4.15 (95% CI: 2.11-8.19) compared with if their peers never used e-cigarettes. The major factors found to motivate university students to use e-cigarettes were the belief that e-cigarettes were less harmful or not harmful (55.0%) and the perception that e-cigarettes were helpful to quit smoking (37.5%). The survey also indicated that 72.4% of the respondents heard about e-cigarettes from television advertisements, 42.7% from websites online, and 41.2% from their parents and friends. CONCLUSIONS: University students who were males, cigarette smokers and whose peers used e-cigarettes were more likely to use e-cigarettes. The use of traditional cigarettes should be controlled strictly in order to reduce the likelihood of e-cigarette use among university students.

9.
J Exp Clin Cancer Res ; 39(1): 157, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795333

RESUMO

BACKGROUND: Many cancer-associated single nucleotide polymorphisms (SNPs) are located in the genomic regions of long non-coding RNAs (lncRNAs). Mechanisms of these SNPs in connection to cancer risk are not fully understood. METHODS: Association of SNP (rs140618127) in lncRNA LOC146880 with non-small cell lung cancer (NSCLC) was evaluated in a case-control study of 2707 individuals. The mechanism of the SNP's biologic influence was explored with in vitro and in vivo experiments, including plasmid transfection, siRNA knockdown, flow cytometry assessment, and assays of cell proliferation, migration, invasion, and colony formation. RESULTS: Association analysis showed that A allele of SNP rs140618127 was associated with low risk of NSCLC in the Chinese population. Lab experiments indicated that SNP rs140618127 contained a binding site for miR-539-5p and the binding between miR-539-5p and LOC146880 resulted in declined phosphorylation of an oncogene, ENO1. The reduced phosphorylation of ENO1 led to decreased phosphorylation of PI3K and Akt, which is further linked to the decline in cell proliferation and tumor progression. CONCLUSION: The study demonstrates that SNP rs140618127 in lncRNA loc146880 provides an alternate binding site for microRNA miR-539-5p which affects the phosphorylation of ENO1 and activation of the PI3K and Akt pathway.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Fosfopiruvato Hidratase/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/genética , Prognóstico , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Nanomedicine ; 28: 102224, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32428675

RESUMO

Anlotinib is a new type of small-molecule multi-target tyrosine kinase inhibitor with inhibitory effects against angiogenesis and tumor growth. An effective targeted nano-delivery system is urgently needed to effectively utilize anlotinib for the treatment of melanoma and lung metastases. In this study, an anlotinib-loaded reduction-sensitive nanomicelle, cyclic RGD peptide (cRGDyk)-anlotinib-reduction sensitive micelles (cARM), was developed as a tumor microenvironment-responsive delivery platform. The micelle carrier was formed by the self-assembly of reduction-sensitive amphiphilic copolymers DSPE-SS-PEG2k and DSPE-PEG2k-cRGDyk. The disulfide bonds in the amphiphilic block of micelles are responsive to elevated GSH in tumor cells for controlled drug release. In a B16F10 tumor-bearing mouse model, cRGDyk-anlotinib-RM (cARM) showed better tumor tissue accumulation and internalization than those for non-reduction-sensitive micelles. Therefore, this reduction-sensitive drug delivery system benefits from its specificity, prolonged blood circulation time, effective absorption by tumor cells, and rapid release of intracellular drugs and is therefore a promising strategy.


Assuntos
Indóis/química , Peptídeos Cíclicos/química , Quinolinas/química , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Melanoma/metabolismo , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Cicatrização/efeitos dos fármacos
11.
Toxins (Basel) ; 12(3)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32210020

RESUMO

Exposure to aflatoxin is considered to be one of the causes of hepatocellular carcinoma (HCC). With the development of bioinformation, we sought to reveal the occurrence and development of aflatoxin-induced HCC through data research. We identified differentially expressed genes (DEGs) of datasets GSE127791 (Aflatoxin-treated pluripotent stem cell derived human hepatocytes vs. controls) and GSE64041 (liver carcinoma with unknown cause vs. non-cancerous tissue) by GEO2R to find the common DEGs. Gene ontology (GO) and KEGG path enrichment analysis were used to annotate the function of DEGs. Hub genes were screened from identified DEGs by protein-protein interaction (PPI) network analysis. The prognostic value of hub genes in cancer databases were evaluated. We obtained 132 common DEGs and 11 hub genes. According to cluster analysis and protein co-expression networks, we screened out the key genes, histidine-rich glycoprotein (HRG) and phosphoenolpyruvate carboxykinase 2 (PCK2). Oncomine database and survival curve analysis showed that the decline in HRG and PCK2 expression in the development of HCC indicated poor prognosis. We speculated that the decreased expression of HRG and PCK2 after aflatoxin exposure to hepatocyte may be related to aflatoxin induced hepatocyte injury and carcinogenesis. In addition, the decreased expression of HRG and PCK2 in the occurrence and development of HCC suggests a poor prognosis of HCC.


Assuntos
Aflatoxinas/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Mapas de Interação de Proteínas/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Neoplasias Hepáticas/genética , Família Multigênica , Análise de Sobrevida
12.
Toxicol Lett ; 323: 1-9, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982503

RESUMO

Zearalenone (ZEA) is a prevalent non-steroidal estrogenic mycotoxin produced mainly by Fusarium contamination. Our previous study showed that ZEA induces the autophagy of Sertoli cells (SCs). However, the underlying mechanisms are still unknown. Several studies have indicated that the increasing level of cytoplasmic Ca2+ could induce autophagy through CaMKKß and AMPK pathways. Thus in order to investigate the potential mechanism underlying ZEA-induced autophagy, the activity of calmodulin-dependent kinase kinase ß(CaMKKß)and AMP-activated protein kinase (AMPK) signaling pathway in ZEA-infected TM4 cells was studied. In the present study, ZEA activated the CaMKKß and AMPK signaling pathways. The AMPK inhibitor and activator significantly inhibited and stimulated the effect of ZEA on AMPK, the transformation from LC3I to LC3II, and the distribution of LC3 dots. In addition, cytosolic calcium (Ca2+) was increased gradually with the concentration of ZEA. After treatment of ZEA-infected cells with 1, 2-bis (2-aminophenoxy) ethane-N, N, N', N'- tetraacetic acid- tetraac etoxymethyl ester (BAPTA-AM) and 2-aminoethyl diphenylborinate (2-APB), the intracellular concentration of Ca2+ reduced significantly. Also, the activities of CaMKKß and AMPK and subsequent autophagy decreased. Moreover, the antioxidant NAC significantly decreased activities of AMPK and autophagy -related protein. Therefore, it can be speculated that ROS- mediated ER-stress induced by ZEA activates AMPK via Ca2+-CaMKKß leading to autophagy in TM4 cells.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Autofagia/efeitos dos fármacos , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/fisiologia , Cálcio/fisiologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Células Cultivadas , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/fisiologia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/fisiologia
13.
Environ Mol Mutagen ; 61(4): 456-464, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31743483

RESUMO

The rodent Pig-a assay has been used extensively as a potential regulatory assay for evaluating the in vivo mutagenicity of test substances. Although the assay can be conducted in different mammalian species, there have been only a few reports describing its use in humans, and rarely in genotoxicant-exposed human populations. In this study, PIG-A mutation frequencies (MFs) were evaluated in 36 azathioprine (AZA; human carcinogen)-treated inflammatory bowel disease (IBD) patients and 36 healthy volunteers. IBD patients exhibited a slight but statistically higher MF (6.10 ± 4.44 × 10-6 ) than healthy volunteers (4.97 ± 2.74 × 10-6 ) (P = 0.0489). The estimated relative risk for the exposed patients was 1.22 which indicated that AZA is a risk factor for inducing PIG-A mutation. However, the PIG-A MF showed no associations with AZA treatment duration or total AZA exposure. In addition, we performed the cytokinesis-block micronucleus test on the same samples. The frequencies of micronuclei (MN) and nuclear buds (NBUD) in IBD patients (MN: 4.70 ± 2.86‰; NBUD: 1.89 ± 0.95‰) were significantly higher than in healthy volunteers (MN: 1.47 ± 0.77‰, P < 0.001; NBUD: 0.90 ± 0.58‰, P = 0.004). MN frequency also had significant correlations with AZA treatment duration (P = 0.011) and total AZA exposure (P = 0.018). Our findings indicate that AZA-treated IBD patients have only a marginally significant increase in PIG-A MF; in contrast, a much stronger AZA-associated increase in genotoxicity was detected with the lymphocyte MN assay. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Antimetabólitos/efeitos adversos , Azatioprina/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Proteínas de Membrana/genética , Mutagênicos/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Taxa de Mutação , Adulto Jovem
14.
Tob Induc Dis ; 17: 30, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31516473

RESUMO

INTRODUCTION: E-cigarettes were invented in China, and most of the world's e-cigarettes have been produced in China. However, awareness and use of e-cigarettes in China are lower than in Europe and America. Against the backdrop of the increasing use of e-cigarettes, the supervision of e-cigarettes in China has been almost non-existent. METHODS: A literature search was carried out in five popular Chinese and English databases. These databases were PubMed, EMBASE, the Cochrane Library, China national knowledge infrastructure (CNKI), and Wan-fang database. RESULTS: Twenty-one studies were identified, and a comprehensive analysis of e-cigarette awareness ratio was conducted for different regions of China and according to gender, age group, and smoking status. We also examined e-cigarette use and associated risk factors, and the relationship between e-cigarette use and smoking cessation. In 2015, the prevalence of 'ever use' and 'current use' of e-cigarettes in China were 3.1% and 0.5%, respectively. The review indicates that the awareness ratio of e-cigarettes was about 66% in Hong Kong, whereas the ratio for Tianjin was lower (43.6%). Online sales were the main channel for selling e-cigarettes to 80% of the users. Awareness of e-cigarettes has been increasing in China. Awareness was higher in men compared to women in all age groups. Nevertheless, e-cigarette use in China was lower than in developed countries. E-cigarette users were more likely to try to quit smoking, but the relationship between e-cigarette use and smoking cessation is still unclear. Governance is necessary for e-cigarette use and marketing effort. CONCLUSIONS: This study investigated the awareness and use of e-cigarettes in China and the existing regulations for e-cigarette use and marketing. The lack of regulations for e-cigarette use and the unrestricted practice encourage the increase in adoption of e-cigarettes and misconceptions of the benefits of using e-cigarettes. Hence, it is crucial that the government of China prioritize the establishment and implementation of regulations for e-cigarette use and marketing.

15.
Molecules ; 24(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284444

RESUMO

Zearalenone (ZEA) interferes with the function of the male reproductive system, but its molecular mechanism has yet to be completely elucidated. Sertoli cells (SCs) are important in the male reproductive system. Silencing information regulator 1 (SIRT1) is a cell metabolism sensor and resveratrol (RSV) is an activator of SIRT1. In this study we investigated whether SIRT1 is involved in the regulation of ZEA-induced lactate metabolism disorder in SCs. The results showed that the cytotoxicity of ZEA toward SCs increased with increasing ZEA concentration. Moreover, ZEA induced a decrease in the production of lactic acid and pyruvate of SCs and inhibited the expression of glycolytic genes and lactic acid production-related proteins. ZEA also led to a decreased expression of SIRT1 in energy receptors and decreased ATP levels in SCs. However, the ZEA-induced cytotoxicity and decline in lactic acid production in SCs were alleviated by the use of RSV, which is an activator of SIRT1. In summary, ZEA decreased lactic acid production in SCs, while the treatment with an SIRT1 activator, RSV, restored the inhibition of lactic acid production in SCs and reduced cytotoxicity of ZEA toward SCs.


Assuntos
Ácido Láctico/metabolismo , Resveratrol/farmacologia , Células de Sertoli/metabolismo , Sirtuína 1/metabolismo , Zearalenona/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Masculino , Ratos Wistar , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-31035709

RESUMO

Zearalenone (ZEA) is a non-steroidal estrogen mycotoxin produced by several Gibberella and Fusarium species. Accumulating evidence has indicated that ZEA strongly stimulates cell proliferation. However the detailed molecular and cellular mechanisms of ZEA-mediated induction of cell proliferation have not yet been completely explained. The aim of this study was to detect the role of miRNAs in ZEA-mediated induction of cell proliferation. The effects of ZEA on cell proliferation were assessed using a cell counting kit assay and xCELLigence system. Micro-RNA sequencing was performed after treatment of TM3 cells with ZEA (0.01 µmol/L) for different time periods (0, 2, 6 and 18 h). Cell function and pathway analysis of the miRNA target genes were performed by Ingenuity Pathway Analysis (IPA). We found that ZEA promotes TM3 cell proliferation at low concentrations. miRNA sequenceing revealed 66 differentially expressed miRNAs in ZEA-treated cells in comparison to the untreated control ( p < 0.05). The miRNA sequencing indicated that compared to control group, there were 66 miRNAs significant change (p < 0.05) in ZEA-treated groups. IPA analysis showed that the predicated miRNAs target gene involved in cell Bio-functions including cell cycle, growth and proliferation, and in signaling pathways including MAPK and RAS-RAF-MEK-ERK pathways. Results from flow cytometry and Western Blot analysis validated the predictions that ZEA can affect cell cycle, and the MAPK signaling pathway. Taking these together, the cell proliferation induced ZEA is regulated by miRNAs. The results shed light on the molecular and cellular mechanisms for the mediation of ZEA to induce proliferation.


Assuntos
Proliferação de Células/efeitos dos fármacos , MicroRNAs/metabolismo , Zearalenona/toxicidade , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Estrogênios Conjugados (USP) , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , MicroRNAs/genética , Transdução de Sinais/efeitos dos fármacos
17.
J Clin Lab Anal ; 33(4): e22858, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30980423

RESUMO

BACKGROUND: It has indicated that single nuclear polymorphisms (SNPs) in the regions encoding non-coding transcripts are associated with lung cancer susceptibility. In a previous microarray study, we identified 13 differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) and associations of SNPs in these lncRNA genes with lung cancer were unknown. We conducted a case-control study to address this issue. METHODS: Using the TaqMan method, we genotyped 17 SNPs located in the 13 lncRNA genes in 1294 cases with NSCLC and 1729 healthy controls. Unconditional logistic regression and Cox proportional hazards regression were used to analyze the associations of these SNPs with NSCLC risk and patient survival, respectively. These analyses were also repeated in subgroups of cases and controls stratified by gender, age group, smoking status, disease stage, and histological type. RESULTS: We identified three SNPs associated with NSCLC risk. For SNP rs498238, CC genotype was associated with lower risk compared to TT genotype (adjusted OR = 0.33, 95%CI: 0.11-0.97, P = 0.043). For rs16901995, CT/TT genotypes were associated with lower risk compared to CC genotype in non-smokers (adjusted OR = 0.78, 95%CI: 0.62-0.98, P = 0.035). Variant genotypes in rs219741 were associated with NSCLC risk in young patients, and the adjusted OR was 1.47 (95%CI: 1.03-2.10, P = 0.033) when compared to the wild genotype. No SNPs were found to be associated with patient overall survival in the study. CONCLUSION: The study suggests that some genetic polymorphisms in the lncRNA genes may influence the risk of NSCLC among Chinese.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
18.
Ecotoxicol Environ Saf ; 175: 263-271, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30903882

RESUMO

Zearalenone (ZEA) is a phenolic resorcylic acid lactone mycotoxin produced by several Fusarium species that grow on temperate and tropical crops. The number of reports documenting the immunotoxic effects of ZEA is increasing, but the underlying mechanism is not clear. The purpose of this study was to investigate the effects of ZEA on T cell chemotaxis and evaluate changes in adhesion and migration proteins associated with this process. Specifically, T cells were isolated from BALB/C mouse splenic lymphocytes, activated by concanavalin A (Con A), and then exposed to different concentrations of ZEA. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used observe the ultrastructural changes inside the cell and on the cell surface, respectively. The transwell migration assay was used to evaluate the effect of ZEA on T cell chemotaxis in the presence of CCL19 or CCL21. A confocal 3D laser was used to capture the morphology of perforated cells and western blot was used to detect the expression of proteins associated with cell migration and adhesion. Additionally, we used flow cytometry to examine the expression of chemokine receptors on T cells. Finally, the chemokine (RANTES and MIP-1α) levels secreted by T cells were assessed using cytometric bead array. Overall, our data showed that treatment with ZEA caused ultrastructural damage on the surface as well as inside of T cells. Moreover, ZEA inhibited T cell chemotaxis which was mediated by CCL19 or CCL21 and disrupted the balance of T cell subtypes. The expression of T cell adhesion and migration proteins was also inhibited by ZEA. The expression of T cell chemokine receptor as well as secretion of RANTES and MIP-1α by T cells was suppressed after ZEA treatment. In summary, our results indicate that ZEA reduced the chemotactic effect of T cells mediated by chemokines, which was likely linked to the inhibition of T cell motility and accompanied by decreased expression of adhesion and migration proteins.


Assuntos
Adesão Celular/efeitos dos fármacos , Quimiocinas/biossíntese , Quimiotaxia/efeitos dos fármacos , Receptores de Quimiocinas/biossíntese , Linfócitos T/efeitos dos fármacos , Zearalenona/toxicidade , Animais , Movimento Celular/efeitos dos fármacos , Quimiocina CCL19/biossíntese , Quimiocina CCL21/biossíntese , Quimiocina CCL5/biossíntese , Citometria de Fluxo , Humanos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia
19.
Food Chem Toxicol ; 126: 262-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825585

RESUMO

Zearalenone (ZEA), a non-steroidal estrogen mycotoxin produced by several species of Fusarium fungi, can be metabolized into many other derivatives by microorganisms, plants, animals and humans. It can affect mammalian reproductive capability by impacting the synthesis and secretion of sex hormones, including testosterone, estradiol and progesterone. This review summarizes the mechanisms in which ZEA and its derivatives disturb the synthesis and secretion of sex steroid hormones. Because of its structural analogy to estrogen, ZEA and its derivatives can exert a variety of estrogen-like effects and engage in estrogen negative feedback regulation, which can result in mediating the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary gland. ZEA and its derivatives can ultimately reduce the number of Leydig cells and granulosa cells by inducing oxidative stress, endoplasmic reticulum (ER) stress, cell cycle arrest, cell apoptosis, and cell regeneration delay. Additionally, they can disrupt the mitochondrial structure and influence mitochondrial functions through overproduction of reactive oxygen species (ROS) and aberrant autophagy signaling ways. Finally, ZEA and its derivatives can disturb the expressions and activities of the related steroidogenic enzymes through cross talking between membrane and nuclear estrogen receptors.


Assuntos
Hormônios Esteroides Gonadais/biossíntese , Mamíferos/fisiologia , Zearalenona/química , Zearalenona/toxicidade , Animais , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Reprodução/efeitos dos fármacos
20.
Toxins (Basel) ; 10(10)2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30274213

RESUMO

A high concentration of Zearalenone (ZEA) will perturb the differentiation of germ cells, and induce a death of germ cells, but the toxic mechanism and molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable role in spermatogenesis. In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively. The data revealed that ZEA could inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase and trigger the autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway. Promoting or inhibiting the level of autophagy could either augment or reverse the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling pathway. Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process.


Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células de Sertoli/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Zearalenona/toxicidade , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Masculino , Ratos Wistar , Células de Sertoli/metabolismo , Transdução de Sinais/efeitos dos fármacos
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