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1.
Psychol Health Med ; : 1-9, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297726

RESUMO

The study aimed to investigate the individual and combined association of health-risk behaviors with mental health among Chinese children. A cross-sectional study was conducted in Wuhan, China, from May to June 2018. Participants self-reported the information on physical activity (PA), screen time (ST), fruit and vegetable (FV) intake, and sleep duration. Mental health, including depression, social anxiety and self-esteem, was assessed using standard questionnaires. A total of 1296 children (704 males and 592 females) aged 9.2 ± 0.4 years were included in the present study. The prevalence of low PA, high ST, low FV intake, and inadequate sleep duration was 45.6%, 18.0%, 69.7%, and 64.7%, respectively. Overall, significant associations were found between individual health-risk behavior and increased risks of mental health. Furthermore, children with three or four health-risk behaviors showed significantly increased risks of anxiety (OR: 3.18, 95%CI: 1.63-6.21), depression (OR: 4.55, 95%CI: 2.28-9.09) and low self-esteem (OR: 3.59, 95%CI: 2.20-5.88) compared with those without health-risk behavior. Results of this study revealed a high prevalence of health-risk behaviors among Chinese children. Furthermore, the clustering of health-risk behavior was associated with significantly increased risks of mental health in this population. Considering these findings, it is important to perform early interventions to reduce children's health-risk behavior and prevent mental health problems.

2.
Arthritis Rheumatol ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964675

RESUMO

OBJECTIVES: To understand the association between obesity-related traits and risk of rheumatoid arthritis (RA), we conducted genetic correlation analysis and two-sample Mendelian randomization (MR) study, using genome-wide genetic data based on >850,000 individuals of European ancestry. METHODS: We collected summary statistics from the hitherto largest GWAS conducted for body mass index (BMI, N=806,810), waist-to-hip ratio (WHR, N=697,734), WHR adjusted for BMI (WHRadjBMI, N=694,649) and RA (Ncase =14,361, Ncontrol =43,923). We conducted cross-trait linkage disequilibrium score regression and ρ-HESS to quantify genetic correlation between pairs of traits (causal overlap). For each obesity-related exposure, we utilized independent, genome-wide significant SNPs (p<5×10-9 ) as instruments to perform MR analysis (causal relationship). We interrogated the causal relationship in both the general population and in a sex-specific manner. We also performed sensitivity analyses to validify MR model assumptions. RESULTS: Despite a negligible overall genetic correlation between the three obesity-related traits and RA, we found significant local genetic correlation from several regions on chromosome 6 (positions 28-29M, 30-35M, 50-52M), highlighting a shared genetic basis. We further observed an increased risk of RA per SD increment (4.8 kg/m2 ) in genetically predicted BMI (OR=1.22; 95%CI: 1.09-1.37). The effect was consistent across sensitivity analyses and comparable between sexes (male: OR=1.22, 95% CI: 1.04-1.44; female: OR=1.19, 95%CI: 1.04-1.36). However, we did not find evidence supporting a causal role of either WHR (OR=0.98; 95%CI: 0.84-1.14) or WHRadjBMI (OR=0.90; 95%CI: 0.79-1.04) in RA. CONCLUSIONS: Genetically predicted BMI significantly increases RA risk. Future studies are needed to understand the biological mechanisms underlying such a link.

3.
Ann Neurol ; 88(6): 1229-1236, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32981134

RESUMO

OBJECTIVE: We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke. METHODS: Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p < 5 × 10-8 ) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non-cases). RESULTS: Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA-I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA-I was attenuated to the null after mutual adjustment. INTERPRETATION: The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA-I needs further investigation. ANN NEUROL 2020;88:1229-1236.

4.
Chemosphere ; 260: 127627, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32673864

RESUMO

Nickel is the most prevailing metal allergen with the highest sensitization rate among the "TOP 25" contact allergens and can affect about 15% of the human population. It is an essential trace metal in plants, animals, and humans. However, the environmental levels of nickel are considerably higher than what is needed for human life. Exposure to high levels of nickel can lead to skin allergies, lung fibrosis, and carcinogenesis. Few existing studies have closely examined the toxicity of nickel, let alone investigated the effective detoxification pathways. Here, we developed a high-throughput screening platform to comprehensively evaluate the nickel toxicity in wild-type C. elegans and explore the underlying detoxification mechanisms in transgenic nematodes. We demonstrated that nickel exerted multiple toxic effects on growth, brood size, feeding, and locomotion in C. elegans. Of which, brood size is the most sensitive endpoint. Nickel was found to first bind to phytochelatin (PC) after entering the worms' body and this PC-Ni complex was further transported by the ABC transporter, CeHMT-1, into the coelomocytes for further detoxification. Our study also demonstrated that the high-throughput screening platform is a promising system for evaluation and investigation of the ecological risks of heavy metals.


Assuntos
Caenorhabditis elegans/fisiologia , Níquel/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Caenorhabditis elegans/metabolismo , Locomoção , Metais Pesados/toxicidade , Nematoides , Níquel/toxicidade , Fitoquelatinas/metabolismo
5.
bioRxiv ; 2020 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-32511346

RESUMO

The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CL pro or M pro ) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CL pro . We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov . These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.

6.
J Agric Food Chem ; 68(22): 6076-6083, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32401500

RESUMO

Carboxylesterases (CarEs) are a multigene superfamily of metabolic enzymes involved in metabolic detoxification of xenobiotics. In this study, an α-esterase gene (BoαE1) was identified from Bradysia odoriphaga. Phylogenetic analysis classified BoαE1 into the α-esterase clade. Developmental expression analysis indicated that BoαE1 was significantly expressed in the second to fourth larval stages. Tissue-specific expression analysis indicated that BoαE1 was highly expressed in the larval midgut. After exposure to LC30 of malathion, the CarE activity of B. odoriphaga was induced and the transcriptional level of BoαE1 was significantly up-regulated. Silencing of BoαE1 significantly increased the susceptibility of B. odoriphaga larvae to malathion. Inhibition assays in vitro indicated that malathion significantly inhibited BoαE1 activity. GC-MS assay showed that BoαE1 possesses hydrolase activity toward malathion and participates in the detoxification of malathion. These results strongly suggest that BoαE1 plays a crucial role in detoxification of malathion in B. odoriphaga.

7.
J Enzyme Inhib Med Chem ; 35(1): 880-896, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32223461

RESUMO

Abnormal alterations in the expression and biological function of retinoid X receptor alpha (RXRα) have a key role in the development of cancer. Potential modulators of RXRα as anticancer agents are explored in growing numbers of studies. A series of (4/3-(pyrimidin-2-ylamino)benzoyl)hydrazine-1-carboxamide/carbothioamide derivatives are synthesised and evaluated for anticancer activity as RXRα antagonists in this study. Among all synthesised compounds, 6A shows strong antagonist activity (half maximal effective concentration (EC50) = 1.68 ± 0.22 µM), potent anti-proliferative activity against human cancer cell lines HepG2 and A549 cells (50% inhibition of cell viability (IC50) values < 10 µM), and low cytotoxic property in normal cells such as LO2 and MRC-5 cells (IC50 values > 100 µM). Further bioassays indicate that 6A inhibits 9-cis-RA-induced activity in a dose-dependent manner, and selectively binds to RXRα-=LΒD with submicromolar affinity (Kd = 1.20 × 10-7 M). 6A induces time-and dose-dependent cleavage of poly ADP-ribose polymerase, and significantly stimulates caspase-3 activity, leading to RXRα-dependent apoptosis. Finally, molecular docking studies predict the binding modes for RXRα-LBD and 6A.

8.
Diabetologia ; 63(7): 1305-1311, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32270255

RESUMO

AIMS/HYPOTHESIS: Observational studies have shown a bidirectional association between major depressive disorder (MDD) and cardiometabolic diseases. We conducted a two-sample bidirectional Mendelian randomisation (MR) study to assess the causal associations of MDD with type 2 diabetes, coronary artery disease (CAD) and heart failure and vice versa. METHODS: We extracted summary-level data for MDD, type 2 diabetes, CAD and heart failure from corresponding published large genome-wide association studies of individuals mainly of European-descent. In total, 96 SNPs for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD and 12 SNPs for heart failure were proposed as instrumental variables at the genome-wide significance level (p < 5 × 10-8). The random-effects inverse-variance weighted method was used for the main analyses. RESULTS: Genetic liability to MDD was significantly associated with type 2 diabetes and CAD at the Bonferroni-corrected significance level. The ORs of type 2 diabetes and CAD were respectively 1.26 (95% CI 1.10, 1.43; p = 6 × 10-4) and 1.16 (95% CI 1.05, 1.29; p = 0.0047) per one-unit increase in loge odds of MDD. There was a suggestive association between MDD and heart failure (OR 1.11 [95% CI 1.01, 1.21]; p = 0.033). We found limited evidence supporting causal effects of cardiometabolic diseases on MDD risk in the reverse MR analyses. CONCLUSIONS/INTERPRETATION: The present study strengthened the evidence that MDD is a potential risk factor for type 2 diabetes and CAD. Whether MDD is causally related to heart failure needs further study. DATA AVAILABILITY: All data included in this study were uploaded as supplements and are also publicly available through published GWASs and open GWAS datasets (UK Biobank, 23andMe and Psychiatric Genomics: https://datashare.is.ed.ac.uk/handle/10283/3203; DIAGRAM: http://diagram-consortium.org/downloads.html; CARDIoGRAMplusCD4: www.cardiogramplusc4d.org/; HERMES: http://www.kp4cd.org/datasets/mi). Graphical abstract.

9.
Int J Behav Med ; 27(4): 400-405, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32096097

RESUMO

BACKGROUND: Adverse childhood experiences (ACEs) have been linked to long-term health outcomes, while the impact of such experience has not been investigated among Zambian youth. This study examined the associations of ACEs with individual and clusters of health risk behavior among college students in Zambia. METHOD: A total of 624 college students participated in this cross-sectional study. A self-administered questionnaire was used to collect information on their ACEs and health risk behaviors. RESULTS: There were 58.3% (364) reporting some forms of ACEs, with 27.6% (172), 16.3% (102), and 14.4% (90) being exposed to 1, 2, and ≥ 3 ACEs, respectively. The prevalence of health risk behaviors ranged from 6.0 to 34.2%. Overall, ACEs were associated with increased risk of smoking, binge drinking, suicide attempt, risky sexual behaviors, and illicit drug use. Logistic regression suggested that participants with ≥ 3 ACEs (OR, 3.62; 95% CI, 2.14-6.13) were more likely to engage in the unhealthy cluster, characterized by the presence of any health risk behavior, than those without ACE. CONCLUSION: ACEs were associated with individual and clustering of health risk behaviors among Zambia college students. Our study suggests that early intervention is needed to prevent long-term adverse health consequences in this population.


Assuntos
Experiências Adversas da Infância , Comportamentos de Risco à Saúde , Estudantes/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Assunção de Riscos , Fumar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Adulto Jovem , Zâmbia
10.
Aging (Albany NY) ; 12(1): 825-843, 2020 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-31929112

RESUMO

BACKGROUND: The correlation between superoxide dismutase 2 (SOD2) V16A variant and urological cancer susceptibility has been widely studied, however, with divergent results. RESULTS: Totally, 9,910 cancer patients and 11,239 control subjects were enrolled. V16A variant is associated with an increased susceptibility to urological cancer (A-allele vs. V-allele: OR = 1.06, 95% CI = 1.00 - 1.13, P = 0.047; AA+AV vs. VV: OR = 1.09, 95% CI = 1.02 - 1.16, P = 0.008), especially for prostate cancer (PCa). Serum SOD2 level of PCa patients with VV+VA genotypes was lower than in those with AA genotypes. SOD2 expression is downregulated in both prostate and bladder cancer, as compared to the control. Furthermore, SOD2 was found to be downregulated in more advanced PCa participants, as compared to the ones in early stages. PCa subjects with low SOD2 expression displayed a shorter disease-free survival (DFS) time compared to that of the high SOD2 expression counterparts. CONCLUSIONS: The SOD2 V16A variant may be associated with increased urological cancer susceptibility, especially for prostate cancer. METHODS: A pooled analysis utilizing odds ratios (ORs), in silico tools and ELISA was adopted to demonstrate this association. We also used immunohistochemical staining (IHS) to assess SOD2 expression.

11.
J Am Coll Health ; 68(6): 587-592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30849021

RESUMO

Objective: This study aimed to assess the impact of a health education intervention on health behaviors, self-efficacy, and well-being among college students. Participants: Between March and October 2016, a total of 532 undergraduates participated. Methods: A theory-based intervention was conducted at Wuhan University, China. Participants were assigned to a control or intervention group (IG). The IG attended a 7-week health education class on knowledge, attitude, and practice of health behaviors. Results: Participants in the IG, compared with those in the control group (CG), reported significantly increased prevalence of high physical activity and regular breakfast, as well as lower screen time, sugar beverage intake, and Internet addiction tendency. Furthermore, intervention students improved in health behavior scores (p = 0.040), compared with the CG, while the changes in subjective well-being and self-efficacy remained similar between the two groups. Conclusions: Health education may promote health behaviors among Chinese college students.

12.
Am J Prev Med ; 58(2): 294-301, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31735481

RESUMO

INTRODUCTION: Evidence on the combined effect of fruit and vegetable intake and total fat intake on hypertension is scarce. This study aimed to explore the relationship among fruit and vegetable intake, fat intake, and hypertension risk among Chinese adults. METHODS: Individuals who participated in the China Health and Nutrition Survey (2004, 2006, 2009, and 2011) and were free of hypertension at baseline (n=4,368) were categorized into quartiles (Q1, lowest; Q4, highest) according to their dietary fruit and vegetable intake and fat intake. Generalized estimation equation models, adjusted for confounders, were used to explore the relationship of fat intake with hypertension and systolic and diastolic blood pressure among all adults and within quartiles of fruit and vegetable intake. Data analyses were performed in 2018. RESULTS: A total of 1,086 adults developed hypertension during follow-up. In the total population, the OR of the highest quartile of fat intake was 1.40 (95% CI=1.12, 1.75) compared with the lowest. Among individuals with low fruit and vegetable intake, the odds of hypertension for those in Q3 (OR=1.97, 95% CI=1.37, 2.83) and Q4 (OR=1.81, 95% CI=1.14, 2.90) of fat intake, compared with individuals in Q1, were even higher than for the overall sample. For each 50-gram increase in FI per day, the ORs of hypertension increased from fat intake Q1 to Q4 among all respondents and those with low fruit and vegetable intake, but not among those with high fruit and vegetable intake. Systolic blood pressure increased by 1.08 mm Hg (95% CI=0.03, 2.13) per 50-gram fat intake per day increment in the fruit and vegetable intake Q1 group, whereas the association was not significant in the fruit and vegetable intake Q2-Q4 groups. CONCLUSIONS: Fruit and vegetable intake modifies the relationship between fat intake and hypertension, whereby high fruit and vegetable intake may offset the detrimental effect of fat intake on hypertension. Increased fruit and vegetable intake and controlled fat intake are recommended to prevent hypertension in Chinese adults.


Assuntos
Pressão Sanguínea , Dieta/estatística & dados numéricos , Gorduras na Dieta/administração & dosagem , Frutas , Hipertensão/epidemiologia , Verduras , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais
13.
Bioorg Med Chem ; 27(20): 115069, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31492533

RESUMO

A novel series of fatty acid synthase (FAS) inhibitors with D-(-)-pantolactone moiety and potential utility for the treatment of obesity were designed, synthesized and characterized, in which the structure of compound 3k was further confirmed by single X-ray diffraction. The mouse FAS inhibitory activity of synthesized compounds was evaluated. Major synthesized compounds (except 3g, 3i, 3k, 3l, and 3n) exhibited moderate FAS inhibitory properties with IC50 values in the range of 13.68 ±â€¯1.52-33.19 ±â€¯1.39 µM, reference inhibitor C75 has IC50 value of 13.86 ±â€¯2.79 µM. Eight compounds (3c, 3d, 3e, 3f, 3j, 3m, 3q and 3r) also displayed inhibitory effect on lipid accumulation in human HepG2 cells. Additionally, the molecular docking study revealed that compound 3m having good inhibition activity against FAS and lipid accumulation also showed promising binding affinities with hFAS, while its binding model with hFAS (PDB ID: 4PIV) was different from that of reference compound C75.


Assuntos
4-Butirolactona/análogos & derivados , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Receptor fas/antagonistas & inibidores , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células Hep G2 , Humanos , Lipídeos/antagonistas & inibidores , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Receptor fas/metabolismo
14.
Mar Drugs ; 17(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470583

RESUMO

Penicillum citreonigrum XT20-134 (MCCC 3A00956) is a fungus with cytotoxic activity, derived from deep-sea sediment. Five new compounds, adeninylpyrenocine (1), 2-hydroxyl-3-pyrenocine-thio propanoic acid (2), ozazino-cyclo-(2,3-dihydroxyl-trp-tyr) (3), 5,5-dichloro-1-(3,5-dimethoxyphenyl)-1,4-dihydroxypentan-2-one (4), and 2,3,4-trihydroxybutyl cinnamate (5), together with 19 known compounds (6-24), were isolated from an ethyl acetate (EtOAc) extract of its fermentation. The structures of the new compounds were comprehensively characterized by high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR). All isolates were evaluated for their cytotoxic activities. The heteroatom-containing new compounds 2 and 4 showed potent cytotoxicity to the human hepatoma tumor cell Bel7402 with IC50 values of 7.63 ± 1.46, 13.14 ± 1.41 µM and the human fibrosarcoma tumor cell HT1080 with IC50 values of 10.22 ± 1.32, 16.53 ± 1.67 µM, respectively.


Assuntos
Organismos Aquáticos/química , Citotoxinas/química , Penicillium/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citotoxinas/farmacologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos
15.
J Agric Food Chem ; 67(36): 9979-9988, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31411878

RESUMO

A delta class glutathione S-transferase gene (BoGSTd2) is identified from Bradysia odoriphaga for the first time. Developmental expression analysis showed that expression of BoGSTd2 is significantly higher in the fourth instar larval stage and the adult stage. Tissue-specific expression analysis found that BoGSTd2 was expressed predominantly in the midgut and Malpighian tubules in the fourth instar larvae and the abdomen of adults. Expression of BoGSTd2 was significantly upregulated following exposure to chlorpyrifos and clothianidin. In vitro inhibition and metabolic assays indicated that recombinant BoGSTd2 could not directly metabolize chlorpyrifos and clothianidin. Nevertheless, disk diffusion assays indicated that BoGSTd2 plays an important role in protection against oxidative stress. RNAi assays showed that BoGSTd2 participates in the elimination of reactive oxygen species induced by chlorpyrifos and clothianidin. These results strongly suggest that BoGSTd2 plays an important role in chlorpyrifos and clothianidin detoxification in B. odoriphaga by protecting tissues from oxidative stress induced by these insecticides.


Assuntos
Dípteros/enzimologia , Glutationa Transferase/metabolismo , Proteínas de Insetos/metabolismo , Inseticidas/metabolismo , Animais , Clorpirifos/metabolismo , Dípteros/genética , Dípteros/crescimento & desenvolvimento , Dípteros/metabolismo , Glutationa Transferase/genética , Guanidinas/metabolismo , Inativação Metabólica , Proteínas de Insetos/genética , Larva/enzimologia , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Neonicotinoides/metabolismo , Estresse Oxidativo , Tiazóis/metabolismo
16.
ACS Appl Mater Interfaces ; 11(31): 27558-27567, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31317730

RESUMO

Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellular functions. Precise quantification of GSH via advanced noninvasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable near-infrared spectroscopy (NIR) absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors. This special ratiometric PAI nanoprobe (CR-POM) is synthesized through the self-assembly of croconaine (CR) dye and molybdenum-based polyoxometalate (POM) clusters with opposite NIR absorbance change in response to GSH. The resulting amplified ratiometric absorbance (Ab866/Ab700), the relatively low limit of detection value (0.51 mM), and the unique acidity-activated self-aggregation contribute to the prolonged intratumoral retention and enhanced tumor accumulation of CR-POM for accurate quantification of intratumoral GSH (0.5-10 mM). Featuring the additional merit of 64Cu radiolabeling for whole-body positron-emission tomography imaging, the smartly designed CR-POM nanoprobe will open new horizons for real-time noninvasive monitoring of biodistribution and simultaneous accurate quantification of GSH levels, especially in tumor and other GSH-related pathophysiological processes.


Assuntos
Corantes Fluorescentes , Glutationa/metabolismo , Nanopartículas , Neoplasias Experimentais , Técnicas Fotoacústicas , Tomografia por Emissão de Pósitrons , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Radioisótopos de Cobre/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo
17.
Chemosphere ; 234: 232-241, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31220657

RESUMO

Heavy metals, a class of persistent environmental toxicants, are harmful to human health. Cd and Pb are two of the most common toxic heavy metals that have been linked with cancers and malfunction of the nervous system. Notably, contamination of Mn usually coexisted with Cd and Pb in environmental and occupational settings. Studies regularly examined the toxic effects on individual metals; however, potential health and toxic effects of mixtures containing two or more heavy metals are unknown. Here, we investigated toxic effects of Cd, Pb, Mn, and their binary and ternary mixtures in the nematode Caenorhabdities elegans. The toxic outcomes, including effects on growth, reproduction, and feeding, were measured via high-throughput platform analysis. The transgenic strain BY250 with GFP in dopaminergic neurons was used to explore the neurodegenerative effects induced by single metals or their mixtures. The combination index(CI) for mixtures effect was calculated using isobolograms methods. Following the exposure, we found significant toxic effects in C. elegans. For single metals, the toxicity order for growth, reproduction, and feeding were Pb > Cd > Mn. For mixtures, the mixture of Cd + Mn induced a less than addictive effect in C. elegans, whereas the mixtures of Cd + Pb, Pb + Mn, and Cd + Pb + Mn induced greater-than-additive effects. Both single metals and their mixtures induced abnormality in dopaminergic neurons. These results showed combinative toxic and neurodegenerative effects of heavy metal mixtures, and future studies will focus on characterization of concentration-response patterns and identification of potential molecular mechanisms in C. elegans model.


Assuntos
Cádmio/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Chumbo/toxicidade , Manganês/toxicidade , Medição de Risco/métodos , Animais , Modelos Biológicos , Testes de Toxicidade
18.
J Agric Food Chem ; 67(13): 3565-3574, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30866622

RESUMO

Two OBP genes, BodoOBP1 and BodoOBP2, were cloned from Bradysia odoriphaga, a major agricultural pest of Chinese chives. The amino acid sequence alignment of both BodoOBPs showed high similarity. Fluorescence competitive binding assays revealed that both BodoOBPs have a moderate binding affinity to dipropyl trisulfide. Tissue expression profiles indicated that both BodoOBPs are antennae-specific and more abundant in the male antennae than in the female antennae. Developmental expression profile analysis indicated that expression levels of both BodoOBPs were higher in the male adult stage than in the other developmental stages. Both BodoOBPs also showed differential expression in pre- and postmating adults. RNAi assays indicated that ability of dsOBPs-treated males to detect females was significantly reduced compared to controls. Attraction of plant volatile dipropyl trisulfide to dsOBPs-treated adults was also significantly lower than in the control. Our findings indicate that both BodoOBPs are involved in host-seeking behavior and in detecting sex pheromones.


Assuntos
Dípteros/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Sequência de Aminoácidos , Animais , Cebolinha-Francesa/parasitologia , Dípteros/química , Dípteros/genética , Dípteros/crescimento & desenvolvimento , Dissulfetos/química , Dissulfetos/metabolismo , Feminino , Proteínas de Insetos/química , Masculino , Dados de Sequência Molecular , Doenças das Plantas/parasitologia , Receptores Odorantes/química , Alinhamento de Sequência
19.
J Agric Food Chem ; 67(10): 2877-2885, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30785752

RESUMO

Fusarium solani H915 (MCCC3A00957), a fungus originating from mangrove sediment, showed potent inhibitory activity against tea pathogenic fungus Pestalotiopsis theae. Successive chromatographic separation on an ethyl acetate (EtOAc) extract of F. solani H915 resulted in the isolation of five new alkenoic diacid derivatives: fusarilactones A-C (1-3), and fusaridioic acids B (4) and C (5), in addition to seven known compounds (6-12). The chemical structures of these metabolites were elucidated on the basis of UV, IR, HR-ESI-MS, and NMR spectroscopic data. The antifungal activity of the isolated compounds was evaluated. Compounds with a ß-lactone ring (1, 2, and 7) exhibited potent inhibitory activities, while none of the other compounds show activity. The ED50 values of the compounds 1, 2, and 7 were 38.14 ± 1.67, 42.26 ± 1.96, and 18.35 ± 1.27 µg/mL, respectively. In addition, inhibitory activity of these compounds against 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene expression was also detected using real-time RT-PCR. Results indicated that compounds 1, 2, and 7 may inhibit the growth of P. theae by interfering with the biosynthesis of ergosterol by down-regulating the expression of HMG-CoA synthase.


Assuntos
Camellia sinensis/microbiologia , Fungicidas Industriais/farmacologia , Fusarium/química , Lactonas/farmacologia , Doenças das Plantas/microbiologia , Água do Mar/microbiologia , Fungicidas Industriais/química , Fungicidas Industriais/isolamento & purificação , Fungicidas Industriais/metabolismo , Fusarium/genética , Fusarium/isolamento & purificação , Fusarium/metabolismo , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/metabolismo , Estrutura Molecular , Xylariales/efeitos dos fármacos , Xylariales/genética , Xylariales/crescimento & desenvolvimento
20.
J Public Health (Oxf) ; 41(2): e169-e176, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29901755

RESUMO

BACKGROUND: Few studies have investigated the effect of smoking on type 2 diabetes in women compared with men, even though several epidemiological studies provided a clear picture of the risk among the entire population. METHODS: We systematically searched PubMed and Embase up to August 2017 for prospective studies that were stratified by sex with measures of the relative risk (RR) for type 2 diabetes and current smoking compared with non-smoking. The sex-specific RRs and their ratios (RRRs), comparing women with man, were pooled using random-effects models. RESULTS: Seventeen articles were identified including 20 prospective cohorts with 5 077 289 participants and 223 084 incident cases of type 2 diabetes. The pooled RRR suggested a similar risk of type 2 diabetes associated with smoking in women compared with men (RRR: 0.98, 95% confidence interval [CI]: 0.96-1.01). Furthermore, no significant sex difference in the RR was found between former smokers and those who had never smoked (RRR: 0.98, 95% CI: 0.92-1.04). CONCLUSIONS: The findings of this meta-analysis indicate that female smokers had similar risk of type 2 diabetes with male smokers.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Fumar/efeitos adversos , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
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