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1.
Oncologist ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784489

RESUMO

BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.

2.
Arch Toxicol ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848666

RESUMO

Deoxynivalenol (DON) cannot be totally removed due to its stable chemical characteristics and chronic exposure to low doses of DON causes significant toxic effects in humans and animals. However, the potential hazard of such low-dose exposure in target organs still remains not completely understood, especially in liver, which is mainly responsible for detoxification of DON. In the present study, we demonstrated for the first time that estimated human daily DON exposure (25 µg/kg bw) for 30 and 90 days caused low-grade inflammatory infiltration around hepatic centrilobular veins, elevated systemic IL-1ß, IL-6 and TNF-α and impaired liver function evidenced by increased serum ALT activity. At the molecular level, expressions of autophagy-related proteins as well as Cleaved Caspase-3 and Cleaved Caspase-7 were upregulated during DON exposure, which indicated the activation of autophagy and apoptosis. Importantly, AAV-mediated liver-specific overexpression of HO-1 reversed DON-induced liver damages, upregulated autophagy and attenuated apoptosis in liver, while AAV-mediated HO-1 silence aggravated DON-induced liver damages, inhibited autophagy and increased apoptosis. Furthermore, in vitro experiments demonstrated that lentivirus-mediated HO-1 overexpression in Hepa 1-6 cells prolonged the duration of autophagy and delayed the onset of apoptosis. HO-1 silence in Hepa 1-6 cells inhibited activation of autophagy and accelerated occurrence of apoptosis, and these could be recovered by CO pre-treatment. Therefore, we suppose that HO-1 might be a potential research target to protect human and animal from liver injuries induced by low dose of DON exposure.

3.
Mutat Res ; 782: 108285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31843139

RESUMO

Mycotoxins, produced by fungi, are secondary metabolites causing adverse, toxic and pathological effects on human and animals. Studies about the association between mycotoxins and microRNAs (miRNAs) were developed since miRNAs have been demonstrated to play a critical role in many developmental processes for regulating messenger RNA (mRNA). As published studies showed, dozens of miRNAs were influenced by mycotoxins, indicating that miRNAs can play important roles in the occurrence and development of mycotoxicosis. Besides, a hypothesis called competing endogenous RNA (ceRNA) was reported to indirectly modulate the expression of mRNA via miRNA response elements (MREs) to consequently regulate cell functions. As a result, four common miRNAs were focused to predict the corresponding ceRNAs based on their own characteristics and the effects of mycotoxins on them, in hope of providing potential ways or directions of miRNAs regulation for mycotoxicosis, and expanding the research field about mycotoxicosis from ceRNA.

4.
Clin Nutr ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31540775

RESUMO

BACKGROUND & AIMS: Drinking water and food are the major sources of strontium in human. Strontium is essential for bone metabolism, while its role in glucose and lipid metabolism is largely unknown. We aimed to investigate the association of strontium, a bone-seeking element, with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) and to further explore the potential mechanisms. METHODS: The case-control study included 1448 newly diagnosed T2DM patients, 782 IGR patients, and 2230 matched controls with normal glucose tolerance. Plasma strontium and other plasma minerals were quantified via inductively coupled plasma mass spectrometry. Multivariable logistic regression analysis was used to evaluate the independent associations between plasma strontium and T2DM and IGR. RESULTS: Plasma strontium was inversely associated with T2DM and IGR. After adjustment for sociodemographic, lifestyle factors, and multiple plasma metals, the odds ratios (95% confidence intervals) of T2DM and IGR were 0.45 (0.35-0.57) and 0.55 (0.43-0.71), respectively, comparing the highest to the lowest quartile of plasma strontium levels. In spline analysis, the odds of T2DM and IGR decreased remarkably with increasing strontium concentration and followed by a plateau. Additionally, plasma strontium was negatively associated with total cholesterol, low density lipoprotein cholesterol, and lipid peroxidation (plasma malondialdehyde level). CONCLUSIONS: The current study indicated that higher plasma strontium concentration was associated with lower odds of T2DM and IGR. Further studies are warranted to confirm these findings and to clarify the underlying mechanisms.

5.
Wei Sheng Yan Jiu ; 48(1): 94-98, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31032775

RESUMO

OBJECTIVE: To explore the effects of deoxynivalenol-induced mRNA expressions of inflammation and apoptosis in BeWo cells. METHODS: After been cultured and transferred, BeWo cells were seeded for the CCK-8 assay. Then incubated with DON in the appropriate doses and time according to the CCK-8 result. ELISA kit was used to measure the ß-HCG levels in BeWo cells. qPCR was used to measure mRNA expressions of inflammation(IL-6, IL-8, TNF-α and Cox-2) and apoptosis(Caspase-3 and Bcl-xl) in BeWo cells. RESULTS: Compared with the control group, IL-6, TNF-α and Cox-2 significantly increased in BeWo cells which were exposed in 50 nmol/L DON in 3, 12 and 24 h(P<0. 01), while IL-8 only significantly increased in 24 h(P<0. 01). Caspase-3 significantly decreased in 3, 12 and 24 h(P<0. 01), and Bcl-xl significantly increased in 24 h(P<0. 01). CONCLUSION: The change in the level of inflammation and apoptosis may be one of the critical molecular mechanisms for DON-induced embryotoxicity.


Assuntos
Apoptose , Citocinas , RNA Mensageiro , Tricotecenos , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Inflamação , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Tricotecenos/farmacologia
6.
Toxicol Appl Pharmacol ; 374: 20-31, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31034930

RESUMO

Deoxynivalenol (DON) is one of the most common mycotoxins which contaminate cereals and their by-products worldwide. Previous studies have stated toxic effects of DON on liver. Heme oxygenase-1 (HO-1) plays a potential role in protecting liver and maintaining gut microbiota homeostasis. Therefore, a study on the potential and basic interaction between DON, HO-1 and intestinal flora would be helpful for better understanding DON-induced hepatotoxicity. In the present study, male C57BL6/J mice were exposed to 25 µg/kg bw/day DON for 30 days. Compared with control group, liver lymphocytes accumulation and elevated ALT activity were observed in DON group, however, AST activity was not notably changed. Several genera, including Parabacteroides and Enterobacter, were significantly increased after DON administration while Lactobacillus, Odoribacter and Lachnospiracea incertae sedis were mostly reduced. The top distinct microbial pathways predicted by PICRUSt included signal transduction, metabolism and genetic information processing. Importantly, liver-specific knockdown of HO-1 caused more severe pathological alterations in liver after DON administration and overexpression of HO-1 protected against DON-induced liver inflammation. The gut microbiota and related microbial pathways were changed in different ways after gene-editing. In conclusion, low dose of DON triggered low-grade inflammation in liver and changes in gut microbiota. HO-1 could attenuate DON-induced inflammation in liver, where gut microbiota may play an important role. HO-1 also could be a potential protective factor between homeostasis of gut microbiota and DON-induced hepatotoxicity in animal models.

7.
Environ Int ; 127: 85-93, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30909097

RESUMO

BACKGROUND: Biomonitoring studies have shown the presence of structurally diverse perfluoroalkyl acids (PFAAs) in humans but only a few studies are available regarding the differential structural effects of PFAAs on human health. OBJECTIVE: The specific association between different structural PFAAs and both gestational diabetes mellitus (GDM) and glucose homeostasis in pregnant women was investigated. METHODS: A prospective nested case-control study including 439 women was conducted during 2013-2015 in Beijing, China. First trimester maternal serum was collected and analyzed for 25 diverse PFAAs with varying carbon chain lengths, linear/branched isomers and carboxylate or sulfonate functional groups. The analyzed PFAAs were grouped into different exposure variables depending on structure characteristics. GDM cases were diagnosed at 24-28 weeks of gestation and individually matched in a 1:2 ratio to controls. Conditional logistic and linear regression was used to evaluate the association between structurally grouped PFAAs and both GDM risk and glucose homeostasis parameters. RESULTS: Among the 25 PFAAs, 12 perfluoroalkyl carboxylates (PFCAs) and 8 perfluoroalkyl sulfonates (PFSAs) were detected in >55.0% of samples and were respectively grouped into different structural groups. The structural-based effect was observed for PFCAs, where short-chain (C4-C7) PFCAs continuous level was significantly associated with GDM with an estimated odds ratio (OR) of 1.99 (95% CI: 1.29, 3.09), and the multivariable-adjusted ORs (95% CI) of GDM for increasing tertiles of short-chain PFCAs were 1.00 (ref.), 1.82 (0.80, 4.16) and 3.01 (1.31, 6.94), P trend = 0.011. Additionally, increased concentration of short-chain PFCAs was significantly associated with higher postprandial glucose levels (P < 0.05). Non-significant association was observed between structure grouped PFSAs and GDM as well as glucose homeostasis. CONCLUSION: This investigation suggests a structure-specific association between short-chain PFCAs exposure and both GDM risk and impaired glucose homeostasis in pregnant women. These findings warrant further investigation with larger samples and a wide range of short-chain PFCAs exposure.


Assuntos
Diabetes Gestacional/sangue , Fluorcarbonetos/sangue , Glucose/metabolismo , Adulto , Glicemia , Ácidos Carboxílicos , Estudos de Casos e Controles , China , Diabetes Gestacional/etiologia , Feminino , Homeostase , Humanos , Razão de Chances , Gravidez , Estudos Prospectivos , Adulto Jovem
8.
Am J Clin Nutr ; 109(2): 1-7, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753322

RESUMO

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography-tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption.


Assuntos
Dieta , Propionatos/sangue , Resorcinóis/sangue , Secale/química , Acidente Vascular Cerebral/sangue , Triticum/química , Grãos Integrais/química , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/prevenção & controle , Estudos de Casos e Controles , Fibras na Dieta/administração & dosagem , Fibras na Dieta/uso terapêutico , Comportamento Alimentar , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/sangue , Acidente Vascular Cerebral/prevenção & controle
9.
Aging Dis ; 10(1): 157-173, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30705776

RESUMO

Skeletal muscle aging is characterized by decline in skeletal muscle mass and function along with growing age, which consequently leads to age-related sarcopenia, if without any preventive timely treatment. Moreover, age-related sarcopenia in elder people would contribute to falls and fractures, disability, poor quality of life, increased use of hospital services and even mortality. Whey protein (WP) and/or resistance training (RT) has shown promise in preventing and treating age-related sarcopenia. It seems that sex hormones could be potential contributors for gender differences in skeletal muscle and age-related sarcopenia. In addition, skeletal muscle and the development of sarcopenia are influenced by gut microbiota, which in turn is affected by WP or RT. Gut microbiota may be a key factor for WP and/or RT against age-related sarcopenia. Therefore, focusing on sex hormones and gut microbiota may do great help for preventing, treating and better understanding age-related sarcopenia.

10.
Thorac Cancer ; 10(2): 156-162, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30480367

RESUMO

BACKGROUND: Mediastinal cystic lesions account for approximately 15-20% of all mediastinal masses and are difficult to differentiate because of similar imaging manifestation. The aim of this study was to differentiate mediastinum cystic lesions through endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) and parameters from cyst-fluid analysis. METHODS: Over a period of eight years, 37 patients suspected with mediastinal cystic lesions were assessed. Cyst fluid was collected via EUS-FNA and further examined using cytological and biochemical techniques. Definitive diagnosis was established based on cytology, surgical pathology, and/or clinical follow-up. RESULTS: Based on the final pathological reports or long-term follow-up, 19 patients were diagnosed with benign cysts, 14 with benign or malignant tumors, 2 with tuberculosis, 1 with an abscess, and 1 with a pancreatic pseudocyst. Computed tomography or magnetic resonance imaging mistakenly distinguished eight cases as solid masses (27.03%), but EUS revealed cystic characteristics. Carcinoembryonic antigen and lactate dehydrogenase (LDH) were evaluated from the cyst fluid obtained by EUS-FNA. There was no statistically significant difference in carcinoembryonic antigen values between benign and malignant cysts; however the average LDH value in the malignancy group was significantly higher than in the benign group. CONCLUSION: EUS-FNA showed great potential for differentiating mediastinal lesions by combining imaging manifestation and cytological examination. The elevated LDH value from cyst fluid chemical analysis could be used as an auxiliary indicator for diagnosing malignancy.

11.
Nutrients ; 10(10)2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279333

RESUMO

The aim of this study was to compare the impact of whole milk supplementation on gut microbiota and cardiometabolic biomarkers between lactose malabsorbers (LM) and absorbers (LA). We performed a pair-wise intervention study of 31 LM and 31 LA, 1:1 matched by age, sex, body mass index, and daily dairy intake. Subjects were required to add 250 mL/day whole milk for four weeks in their routine diet. At the beginning and the end of the intervention period, we collected data on gut microbiota and cardiometabolic biomarkers. Whole milk supplementation significantly increased Actinobacteria (P < 0.01), Bifidobacterium (P < 0.01), Anaerostipe (P < 0.01), and Blautia (P = 0.04), and decreased Megamonas (P = 0.04) in LM, but not LA. Microbial richness and diversity were not affected. The fecal levels of short-chain fatty acids (SCFAs) remained stable throughout the study. Body fat mass (P < 0.01) and body fat percentage (P < 0.01) reduced in both groups, but the changes did not differ between groups. No significant differences in other cardiometabolic markers were found between LM and LA. When compared with LA, whole milk supplementation could alter the intestinal microbiota composition in LM, without significant changes in fecal SCFAs and cardiometabolic biomarkers.


Assuntos
Dieta/métodos , Microbioma Gastrointestinal/fisiologia , Intolerância à Lactose/sangue , Intolerância à Lactose/microbiologia , Leite/metabolismo , Actinobacteria/isolamento & purificação , Adulto , Animais , Bifidobacterium/isolamento & purificação , Biomarcadores/sangue , Fezes/microbiologia , Feminino , Humanos , Masculino , Leite/química , Adulto Jovem
12.
BMC Health Serv Res ; 18(1): 635, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30103736

RESUMO

BACKGROUND: Quota payment for specific diseases under global budget is one of the most typical modes of provider payment system reform in rural China. This study aimed to assess this reform mode from aspects of the total fee, structure of the fee and enrollees' benefits. METHODS: A total of 127,491 inpatient records from 2014 to 2016 were extracted from the New Rural Cooperative Medical Scheme (NRCMS) database in Weiyuan County, Gansu Province. Total fee, actual compensation ratio, out-of-pocket ratio, constituent ratio of the treatment fee, constituent ratio of the inspection and laboratory fee, and length of stay were selected as dependent variables. Both generalized additive models (GAMs) and multiple linear regression models were used to measure the change in dependent variables along with year. RESULTS: Prior to the adjustment of the compensation type, out-of-pocket ratio and length of stay decreased, while total fee, actual compensation ratio, constituent ratio of the treatment fee, and constituent ratio of the inspection and laboratory fee increased. After the compensation type was adjusted, the mean of the total fee increased rapidly in 2015 and remained stable in 2016. The mean length of stay increased in 2015 but decreased in 2016. A comparison of inpatients suffering from diseases covered by quota payments and those suffering from general diseases revealed that total fee, out-of-pocket ratio, and length of stay decreased and actual compensation ratio increased for the former, whereas the opposite was true for the latter. Constituent ratio of the treatment fee and constituent ratio of the inspection and laboratory fee increased for both samples, except for the constituent ratio of the inspection and laboratory fee of quota payment diseases in 2016, which did not change. CONCLUSIONS: Quota payment for specific diseases under global budget had obviously positive effects on cost control in Weiyuan, Gansu. Considering the limited coverage of quota payment for diseases, the long-term effect of this reform mode and its replicability awaits further evaluation.


Assuntos
Controle de Custos , Gastos em Saúde/estatística & dados numéricos , Hospitalização/economia , Mecanismo de Reembolso , Serviços de Saúde Rural/economia , Orçamentos , China , Humanos , Renda , Modelos Lineares , Recursos Humanos
13.
Food Chem Toxicol ; 112: 342-354, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29331731

RESUMO

Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and grain products. DON contamination in fodder and food is a serious threat for health, since it impairs the immune and gastrointestinal systems of both human and animals. Gut microbiota seems to play a more and more important part in human and animals' health according to related researches. Previous studies implied some associations among gut microbiota, DON and immune system. For example, DON affects immune system as well as the composition and abundance of gut microbiota, and the latter influences immune system as well. In the present short review, we not only provide the available information about the toxic consequences of DON-induced immunotoxicity on different animals and cell lines and discuss its main possible molecule mechanisms, but also summarize research results concerning the role of gut microbiota in DON-induced immunotoxicity and gender differences, with the aim to find some potential therapeutic strategies to tackle DON-induced immunotoxicity.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Tricotecenos/toxicidade , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Humanos , Intestinos/microbiologia
14.
Diabetes Care ; 41(3): 440-445, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29263162

RESUMO

OBJECTIVE: To examine the association of plasma alkylresorcinol metabolite 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, with type 2 diabetes (T2D) and impaired glucose regulation (IGR) in a Chinese population. RESEARCH DESIGN AND METHODS: A total of 1,060 newly diagnosed T2D patients, 736 newly diagnosed IGR patients, and 1,443 control subjects with normal glucose tolerance were recruited in the case-control study. Plasma DHPPA concentrations were determined by high-performance liquid chromatography-tandem mass spectroscopy. Multivariate logistic regression analysis was used to evaluate the independent association of plasma DHPPA concentrations with the likelihood of T2D and IGR. RESULTS: After adjustment for age, sex, BMI, and family history of diabetes, the odds ratios (95% CI) of T2D and IGR were 0.57 (0.45, 0.73) and 0.66 (0.50, 0.85), respectively, comparing the lowest with the highest quartile of plasma DHPPA concentrations. Further adjustment for current smoking status, current alcohol consumption, physical activity, history of hypertension, and educational level did not change the observed association materially. Similar results were also obtained in T2D and IGR groups combined. The inverse association of plasma DHPPA with T2D persisted in stratified analyses according to age, sex, BMI, current smoking status, current alcohol consumption, physical activity, family history of diabetes, and history of hypertension. CONCLUSIONS: These findings suggested that higher plasma DHPPA concentrations were associated with lower odds of T2D and IGR. Further studies are warranted to confirm these findings in prospective cohorts.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Intolerância à Glucose/sangue , Fenilpropionatos/sangue , Secale , Triticum , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , China , Diabetes Mellitus Tipo 2/etiologia , Dieta , Feminino , Intolerância à Glucose/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resorcinóis/sangue , Fatores de Risco
15.
Am J Clin Nutr ; 106(3): 888-894, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28724646

RESUMO

Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent.Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms.Design: This was an age- and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped.Results: Medians (IQRs) of plasma TMAO concentration were 1.47 µmol/L (0.81-2.20 µmol/L) for controls and 1.77 µmol/L (1.09-2.80 µmol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) (P-trend < 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed (P = 0.093).Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials.gov as NCT03130894.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Metilaminas/sangue , Óxidos/sangue , Adulto , Carnitina/sangue , Estudos de Casos e Controles , Colina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Feminino , Genótipo , Humanos , Intestinos/microbiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Oxigenases/genética , Oxigenases/metabolismo , Polimorfismo Genético
16.
Toxins (Basel) ; 9(6)2017 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-28598396

RESUMO

Deoxynivalenol (DON) belongs to the type B group of trichothecenes family, which is composed of sesquiterpenoid metabolites produced by Fusarium and other fungi in grain. DON may cause various toxicities, such as cytotoxicity, immunotoxicity, genotoxicity as well as teratogenicity and carcinogenicity. In the present study, we focus on a hypothesis that DON alters the expressions of Nrf2/HO-1 pathway by inducing embryotoxicity in C57BL/6 mouse (5.0, 2.5, 1.0, and 0 mg/kg/day) and BeWo cell lines (0 and 50 nM; 3 h, 12 h and 24 h). Our results indicate that DON treatment in mice during pregnancy leads to ROS accumulation in the placenta, which results in embryotoxicity. At the same time Nrf2/HO-1 pathway is up-regulated by ROS to protect placenta cells from oxidative damage. In DON-treated BeWo cells, the level of ROS has time-effect and dose-effect relationships with HO-1 expression. Moderate increase in HO-1 protects the cell from oxidative damage, while excessive increase in HO-1 aggravates the oxidative damage, which is called in some studies the "threshold effect". Therefore, oxidative stress may be the critical molecular mechanism for DON-induced embryotoxicity. Besides, Nrf2/HO-1 pathway accompanied by the "threshold effect" also plays an important role against DON-induced oxidative damage in this process.


Assuntos
Embrião de Mamíferos/efeitos dos fármacos , Estresse Oxidativo , Tricotecenos/toxicidade , Animais , Doenças do Desenvolvimento Ósseo/induzido quimicamente , Linhagem Celular , Embrião de Mamíferos/anormalidades , Feminino , Glutationa/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Malondialdeído/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Placenta/efeitos dos fármacos , Placenta/metabolismo , Placenta/patologia , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo
17.
J Appl Toxicol ; 37(9): 1021-1029, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28466983

RESUMO

Deoxynivalenol (DON) is one of the most important mycotoxins in cereal-based foods or other food productions, produced by Fusarium species. Because of the high occurrence of DON in food combined with vast consumption of cereals and grain worldwide, the DON-contaminated food is a very harmful factor for human and animal health. DON has been reported to induce anorexia at lower or chronic doses in animal models. However, further researches for DON-induced anorexia are limited. Previous publications demonstrated a close link between Bacteroidetes and Firmicutes, two kinds of gut microbiota, with weight loss and the effect of low administration of DON on neurotransmitters in the frontal cortex, cerebellum, hypothalamus, hippocampus and pons/medulla. These data are similar to other studies, which show selective 5HTα receptor agonists apparently causing hyperphagia whereas 5HT1ß agonists appear to induce anorexia. Thus, the neurochemical effects of lower DON exposure can be as a result of peripheral toxicological events such as emesis, which overwhelmed its more subtle feed refusal activity. Besides, changes in the microbiota have an impact on stress-related behaviors like anxiety and depression, which can lead to weight loss through decreased feed intake. Gut dysbiosis is also associated with brain dysfunction and with behavioral changes. These conclusions illustrate as well a potential explanation for DON-induced anorexia.In this review, we summarize information about DON-induced anorexia from previous studies and provide our opinion for future investigations that could establish a link between gut microbiota, neurotransmitters, anorexia and weight loss under the DON exposure. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Anorexia/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tricotecenos/toxicidade , Animais , Anorexia/induzido quimicamente , Dieta , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Comportamentos Relacionados com a Saúde , Humanos , Neurotransmissores/farmacologia , Peptídeos/metabolismo , Serotonina/metabolismo , Perda de Peso/efeitos dos fármacos
18.
Toxicol In Vitro ; 41: 150-158, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28286114

RESUMO

Deoxynivalenol (DON) is a toxic fungal secondary metabolite produced by molds of the Fusarium genus, and it is known to cause a spectrum of diseases both in humans and animals, such as emesis, diarrhea, anorexia, immunotoxicity, hematological disorders, impairment of maternal reproduction, and fetal development. The recently revealed teratogenic potential of DON has received much attention. In various animal models, it has been shown that DON led to skeletal deformities of the fetus. However, the underlying mechanisms are not yet fully understood, and toxicological data are also scarce. Several animal research studies highlight the potential link between morphological abnormalities and changes of autophagy in the reproductive system. Because autophagy is involved in fetal development, maintenance of placental function, and bone remodeling, this mechanism has become a high priority for future research. The general aim of the present review is to deliver a comprehensive overview of the current state of knowledge of DON-induced reproductive toxicity in different animal models and to provide some prospective ideas for further research. The focus of the current review is to summarize toxic and negative effects of DON exposure on the reproductive system and the potential underlying molecular mechanisms in various animal models.


Assuntos
Feto/efeitos dos fármacos , Genitália/efeitos dos fármacos , Teratogênios/toxicidade , Tricotecenos/toxicidade , Animais , Autofagia/efeitos dos fármacos , Feto/anormalidades , Humanos
19.
J Appl Toxicol ; 37(7): 784-791, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28138998

RESUMO

Deoxynivalenol (DON), one of trichothecene mycotoxins produced by the fungus Fusarium, is commonly detected in cereal foods and in secondary food production across the world. Lower concentrations of DON induce a dose-related feed refusal (anorexia), whereas it acts as a potent emetic agent at higher levels. DON-induced emesis in humans and livestock can be observed and recorded in both undeveloped and developed regions such as Lixian, Guide and Huangzhong in China and Illinois in the USA. Some studies with different animal models (pigs and minks) suggested that DON could change expressions of 5-hydroxytryptamine, peptide YY, neuropeptide Y2 receptor and nucleobindin-2/nesfatin-1 in plasma and different areas of the brain. Some selective antagonist of 5-hydroxytryptamine 3 receptors can inhibit DON-induced emetic response. Otherwise, the Ca2+ homeostasis and MAPK pathway could be potential directions in future studies. Dolasetron, dantrolene and JNJ-31020028 can be used in clinical treatment but they have potential toxic effects. (-)Epicatechin, ginger phytochemicals and isoflavone can be tested in in vitro and in vivo for their usage as food additives for reducing the emesis. The present review summarizes and discusses some information from previous and recent prominent publications with the aim to provide some comprehensive and helpful data for understanding the mechanism of DON-induced emesis. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Micotoxinas/farmacocinética , Micotoxinas/toxicidade , Tricotecenos/farmacocinética , Tricotecenos/toxicidade , Vômito/induzido quimicamente , Vômito/fisiopatologia , Animais , China , Humanos , Estudos Prospectivos
20.
J Appl Toxicol ; 37(1): 60-70, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27456930

RESUMO

Deoxynivalenol (DON, also known as vomitoxin) is a common mycotoxin found worldwide, especially in contaminated food. DON is toxic to a variety of cells and tissues in humans. Three kinds of conjugated products (DON-3-glucuronide, DON-15-glucuronide and DON-7-glucuronide) can be found as major metabolites in human urine. Females and males show different patterns of exposure levels, and human exposure to DON also shows some geographical differences because of different DON levels in cereal-based foods, food intake habits and UDP-glucuronosyltransferase expression. Specifically, the C12, 13-deepoxy metabolite was found predominantly in French adults but was rarely detected in UK adults. However, a cohort of Spanish individuals demonstrated even lower DON levels than the levels in the UK populations, whereas a very high DON exposure level was detected in South Africa and Linxian, China. Recent publications have further indicated that DON could be detected in the urine of pregnant women from different countries, which suggests that there is a potential risk to both mothers and foetuses. Additionally, phytochemicals have been shown to be less toxic to cells and laboratory animals in research studies and may also be used as food additives for reducing the toxic effects of DON. In this review, we provide global information on DON metabolism, human exposure and gender differences in humans. Also, control strategies for this mycotoxin are discussed. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/análise , Poluentes Ambientais/metabolismo , Tricotecenos/análise , Tricotecenos/metabolismo , África , Biomarcadores/sangue , Biomarcadores/urina , China , Monitoramento Ambiental , Europa (Continente) , Feminino , Humanos , Masculino , Vigilância da População , Fatores Sexuais
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