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1.
Artigo em Inglês | MEDLINE | ID: mdl-32016391

RESUMO

OBJECTIVES: This study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the association of bile acids with GDM risk or had an interactive effect with bile acids on GDM risk. DESIGN: We conducted a 1:1 nested case-control study (n=486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational weeks). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk. RESULTS: Of the six detectable LPCs, LPC14:0 <0.24 nmol/mL, LPC15:0 ≥0.45 nmol/mL and LPC18:0 ≥18.00 nmol/mL were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, presence of DCA ≤0.36 nmol/mL greatly amplified the adjusted OR of LPC18:0 ≥18.00 nmol/mL alone for GDM from 8.18(2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, presence of GUDCA ≤0.07 nmol/mL also greatly amplified the adjusted OR of LPC18:0 ≥18.00 nmol/mL alone for GDM from 17.2(1.77-168) up to 73.8 (12.7-429), with significant additive interaction. CONCLUSIONS: LPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM and its molecular mechanism is worth further investigations.

2.
Sci Total Environ ; 712: 136543, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050385

RESUMO

In karst regions, shallow karst fissure (SKF) soil has proven to be an important plant habitat and soil resource. However, how plants affect the microbial abundance and community composition of SKF soil remains poorly studied. We explored the soil microbial community structure differences in fractured soil-plant systems by determining phospholipid fatty acid (PLFA) profiles under three vegetation types (herbs, shrubs and trees) in SKF and used a bare SKF without vegetation as the control in a karst rocky desertification area. The total microbial biomass and microbial community composition differed between surface soil and SKF soil. The total microbial biomass in surface soil was higher than that in SKF soil. In addition, in contrast to surface soil, the microbial communities in SKF soil were more vulnerable to the effects of environmental variables. Furthermore, plants had a significant positive effect on the accumulation of microbial biomass in surface and SKF soil: shrubs had the strongest effect, followed by trees. Vegetation types significantly affected the ratios of saturated PLFAs to monounsaturated PLFAs (SAT/MONO ratio) and cyclopropyl PLFAs to precursors (cy/pre ratio). In contrast to the SKF without vegetation, the SAT/MONO ratio and cy/pre ratio under grasslands, shrublands and trees were low. Herbs and shrubs had the greatest capacity to enhance the ability of soil to respond to environmental stress compared to trees. Our results suggest that, as an important plant habitat in karst regions, the condition of SKF soil should be urgently improved. The stereoscopic collocation of shrub-grass vegetation may be the preferred measure for vegetation restoration. Deep-rooted shrubs and grasses are best at improving soil and plant growth. Our study can be useful for developing strategies for vegetation rehabilitation in karst regions.

3.
J Nutr ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32006008

RESUMO

BACKGROUND: The associations of different adiposity indicators and short-term adiposity change with diabetes risk are not fully elucidated. OBJECTIVE: We aimed to assess the independent and joint effects of different baseline adiposity indicators and short-term body adiposity change on the risk of type 2 diabetes. METHODS: We prospectively followed 10,419 Chinese adults aged 20-80 y in 2008-2012. Incident diabetes was diagnosed based on fasting glucose, 2-h glucose, or glycated hemoglobin (HbA1c) after an oral glucose tolerance test using the American Diabetes Association standard. Cox proportional hazard regression models were used to assess the associations of adiposity indicators and adiposity change with diabetes risk. RESULTS: During a mean follow-up of 2.8 y, we identified 805 type 2 diabetes cases. Baseline BMI, waist circumference, and waist-height ratio (WHtR) were all positively associated with diabetes risk. The area under the curve was significantly greater for waist circumference (0.624) and WHtR (0.627) than for BMI (0.608) (P <0.05). Compared with subjects with stable adiposity levels (±2 kg or ± 3 cm in changes in body weight or waist circumference) from baseline to Year 1, those subjects with the most weight gain or the most waist circumference gain had a 1.53-fold or 1.37-fold greater risk of diabetes; those with the most weight loss had a 46% lower risk of diabetes. Furthermore, regardless of baseline weight status, weight or waist circumference change in the first year was associated with diabetes risk. CONCLUSION: Abdominal adiposity indicators, waist circumference and its change, are more strongly associated with the risk of type 2 diabetes than general adiposity indicators, BMI, and changes in body weight among Chinese adults.

4.
Endocrine ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32006292

RESUMO

AIMS: The association between ß-cell function and glycemic variability remains to be clarified in insulin-treated patients with type 2 diabetes. Therefore, the study sought to examine the association of various indices of ß-cell function with glycemic variability in Chinese insulin-treated patients with type 2 diabetes. METHODS: Glycemic variability was assessed by the coefficient of variation (CV) of glucose levels with the use of continuous glucose monitoring (CGM). Basal ß-cell function was evaluated by fasting C-peptide (FCP) and the homeostasis model assessment 2 for ß-cell function (HOMA2-%ß). Postload ß-cell function was measured by 2-hour C-peptide (2hCP) and the acute C-peptide response (ACPR) to arginine. RESULTS: When a cutoff value of CV ≥ 36% was used to define unstable glucose, the multivariable-adjusted odds ratios for labile glycemic control were 0.34 (95% CI 0.18-0.64) for each 1 ng/mL increase in ACPR, 0.47 (95% CI 0.27-0.81) for each 1 ng/mL increase in FCP, 0.77 (95% CI 0.61-0.97) for each 1 ng/mL increase in 2hCP, and 1.00 (95% CI 0.98-1.01) for each 1% increase in HOMA2-%ß. When we further adjusted for 2hCP and HOMA2-%ß in the ACPR and FCP analyses, and adjusted for ACPR or FCP in the 2hCP analyses, only ACPR but not FCP or 2hPC remained to be a significant and inverse predictor for labile glycemic control. CONCLUSIONS: ACPR evaluated by the arginine stimulation test may be superior to other commonly used ß-cell function parameters to reflect glycemic fluctuation in insulin-treated patients with type 2 diabetes.

5.
Med Care ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32011424

RESUMO

BACKGROUND: Electronic health records (EHRs) and claims records are widely used in defining type 2 diabetes mellitus (T2DM) complications across different types of health care encounters. OBJECTIVE: This study investigates whether using different EHR encounter types to define diabetes complications may lead to different results when examining associations between diabetes complications and their risk factors in patients with T2DM. RESEARCH DESIGN: The study cohort of 64,855 adult patients with T2DM was created from EHR data from the Research Action for Health Network (REACHnet), using the Surveillance Prevention, and Management of Diabetes Mellitus (SUPREME-DM) definitions. Incidence of coronary heart disease (CHD) and stroke events were identified using International Classification of Diseases (ICD)-9/10 codes and grouped by encounter types: (1) inpatient (IP) or emergency department (ED) type, or (2) any health care encounter type. Cox proportional hazards regression was used to estimate associations between diabetes complications (ie, CHD and stroke) and risk factors (ie, low-density lipoprotein cholesterol and hemoglobin A1c). RESULTS: The incidence rates of CHD and stroke in all health care settings were more than twice the incidence rates of CHD and stroke in IP/ED settings. The age-adjusted and multivariable-adjusted hazard ratios for incident CHD and stroke across different levels of low-density lipoprotein cholesterol and hemoglobin A1c were similar between IP/ED and all settings. CONCLUSION: While there are large variations in incidence rates of CHD and stroke as absolute risks, the associations between both CHD and stroke and their respective risk factors measured by hazard ratios as relative risks are similar, regardless of alternative definitions.

6.
Prim Care Diabetes ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918978

RESUMO

AIMS: This study aimed to examine impacts of gestational diabetes mellitus (GDM) on quality of life (QoL) domains in Chinese pregnant women. METHODS: We recruited 13,358 pregnant women in Tianjin, China. GDM was diagnosed using the criteria of International Association of Diabetes and Pregnancy Study Group. QoL was measured using the 36-Item Short-Form Health Survey. General linear model was used to obtain ß-coefficient and 95% confidence intervals (CI) of GDM for QoL domain and summary scores. RESULTS: 7.25% of the pregnant women developed GDM. Among the QoL domain and summary scores, only general health (GH) score was lower in the GDM group than in the non-GDM group. GDM and advanced maternal age (i.e., ≥ versus <30 years) were negatively associated with GH in multivariable analyses (ß-coefficient: -1.17, 95%CI: -2.17 to -0.17 & -0.79, -1.40 to -0.18, respectively). In subgroup analyses, the ß-coefficient of GDM for GH among women with maternal age ≥30 years was enhanced to -2.17 (-3.94 to -0.40) in multivariable analysis while the ß-coefficient of GDM for GH among women aged <30 years was attenuated to non-significance. CONCLUSIONS: GDM and advanced maternal age were associated with reducing GH, and presence of advanced maternal age markedly increased the effect of GDM on GH.

7.
Sleep Health ; 6(1): 4-14, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31699637

RESUMO

INTRODUCTION: Previous studies have linked short sleep duration, poor sleep quality, and late sleep timing with lower health-related quality of life (HRQoL) in children. However, almost all studies relied solely on self-reported sleep information, and most studies were conducted in high-income countries. To address these gaps, we studied both device-measured and self-reported sleep characteristics in relation to HRQoL in a sample of children from 12 countries that vary widely in terms of economic and human development. METHODS: The study sample included 6,626 children aged 9-11 years from Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Waist-worn actigraphy was used to measure total sleep time, bedtime, wake-up time, and sleep efficiency on both weekdays and weekends. Children also reported ratings of sleep quantity and quality. HRQoL was measured by the KIDSCREEN-10 survey. Multilevel regression models were used to determine the relationships between sleep characteristics and HRQoL. RESULTS: Results showed considerable variation in sleep characteristics, particularly duration and timing, across study sites. Overall, we found no association between device-measured total sleep time, sleep timing or sleep efficiency, and HRQoL. In contrast, self-reported ratings of poor sleep quantity and quality were associated with HRQoL. CONCLUSIONS: Self-reported, rather than device-based, measures of sleep are related to HRQoL in children. The discrepancy related to sleep assessment methods highlights the importance of considering both device-measured and self-reported measures of sleep in understanding its health effects.

8.
Theor Appl Genet ; 133(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31549182

RESUMO

KEY MESSAGE: A whole genome bin map was developed for a MAGIC population. Association studies for heading date at bin level exhibited powerful QTL mapping and identified favorable alleles. The presumed advantages of multiparent advanced generation intercross (MAGIC) population in quantitative trait locus (QTL) mapping were not fully utilized in the previous studies in which genome-wide association studies (GWAS) were conducted at only single nucleotide polymorphism level. In this study, we genotyped a rice four-way MAGIC population of 247 F7 lines and their parents by sequencing. A total of 5934 bins with an average length of 65 kb were constructed and covered 97% of the genome. The MAGIC population showed low population structure and balanced parental contributions. A bin-based GWAS for heading date identified 4 QTLs in three environments. Three major QTLs were mapped exactly to the bins where the major heading date genes DTH3, Ghd7.1 and Ghd8 were located. Multiple comparisons showed that different parental alleles had varied genetic effects. Like DTH3, the alleles of the Guichao 2/YJSM, IR34 and Cypress had larger, intermediate and no effects, respectively. Based on comparative sequencing of 8 known heading date genes undetected in this MAGIC population, only Ghd7 exhibited diverse function among parents. The failure in Ghd7 mapping was well explained by its interaction with Hd1 because Ghd7 had no effects on heading date when combined with the nonfunctional hd1 carried by all four parents. Overall, bin-based GWAS have more mapping power and higher resolution with a MAGIC population and provide favorable alleles to breeders. The use of more diversified parents is encouraged to develop a MAGIC population for detecting more QTLs for important agronomical traits.

9.
CNS Neurosci Ther ; 26(2): 228-239, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31364823

RESUMO

AIMS: As a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD). METHODS: Adult AQP4 null mice and wild-type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses. RESULTS: Aquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of ß-amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT-SD mice. CONCLUSION: These results demonstrate that AQP4-mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep-related disorders.

10.
Bioresour Technol ; 295: 122230, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669870

RESUMO

To overcoming the natural recalcitrance of cellulose for glucose production via enzymatic hydrolysis, a new strategy of destroying hydrogen bond donor to reconstruct cellulose's hydrogen bonding network was developed via a mild reversible reaction of cellulose with CO2 catalyzed by organic bases. The reaction dynamics of cellulose with CO2 in the presence of organic bases was studied by using in situ IR. Investigation also included how the organic bases in pretreatment media and pretreatment parameters including CO2 pressure, pretreatment temperature and time affected the physical-chemical structure of cellulose by Fourier Transform Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Atomic force microscopy (AFM) and subsequent enzymatic scarification of cellulose. The findings showed that dissolution activation efficiency significantly correlated to various parameters, that can be optimized to be the tetramethyl guanidine (TMG)/CO2/DMSO solvent system at 50 °C, 2 MPa of CO2 for 2 h, by which a complete transformation the cellulose crystalline structure from I to II, and 100% glucose yield were achieved. The recyclability and usability are also investigated.


Assuntos
Dióxido de Carbono , Celulose , Hidrólise , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
11.
J Nanosci Nanotechnol ; 20(4): 2239-2246, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492233

RESUMO

Spherical manganese carbonate (MnCO³) templates were successfully prepared by a facile chemical precipitation method. The size of the as-prepared samples was changed by adjusting the ratio of MnSO4·H2O and NaHCO3 (1:1, 1:5, 1:10 and 1:15). More interestingly, when adding Na2SO4 to the reaction solution, the morphology of MnCO³ further evolved from an irregular spheroid to a cube. Next, spherical and cubic MnCO³ particles with the most uniform size were selected as precursor templates to synthesize intermediate compounds (MnCO³/MnS/MoS2). Eventually, MoS2 microspheres and microcubes with a hollow structure were obtained by removing the MnCO³ and MnS with acid pickling. The structure, morphology and elemental composition of the products were characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectrometry (EDS). The results of the photocatalytic experiments show that hollow MoS2 prepared with an MnCO³ template exhibited excellent photocatalytic performance. Therefore, the application of a template method to prepare hollow structure materials is worthy of further study in the photocatalysis field.

12.
J Clin Endocrinol Metab ; 105(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529060

RESUMO

CONTEXT: Very few studies focused on the association between body mass index (BMI) and stroke risk among patients with diabetes. OBJECTIVE: We aimed to investigate the association between BMI and stroke risk in patients with type 2 diabetes. DESIGN: Demographic, anthropometric, laboratory, and medication information were extracted from the National Patient-Centered Clinical Research Network common data model. PARTICIPANTS: We performed a retrospective cohort study of 67 086 patients with type 2 diabetes. MAIN OUTCOME MEASURES: Incident stroke including both ischemic and hemorrhagic stroke were defined. RESULTS: During a mean follow up of 3.74 years. 8918 incident stroke events occurred. Multivariable-adjusted hazard ratios across different categories of BMI at baseline (18.5-24.9 [reference group], 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40 kg/m2) were 1.00, 0.92, 0.85, 0.74, and 0.63 (Ptrend <0.001) for total stroke; 1.00, 0.93, 0.88, 0.77, and 0.65 (Ptrend <0.001) for ischemic stroke; and 1.00, 0.79, 0.50, 0.50, and 0.41 (Ptrend <0.001) for hemorrhagic stroke, respectively. When we used an updated mean value of BMI, the graded inverse association of body mass index with stroke risk did not change. This linear association was consistent among patients of different subgroups. Further sensitivity analysis excluding patients who were diagnosed stroke within 6 months after first diagnosis of type 2 diabetes or including non-smokers only also confirmed our findings. CONCLUSION: The present study found an inverse association between BMI and the risk of total, ischemic, and hemorrhagic stroke among patients with type 2 diabetes. More clinical and molecular insights are still needed in explaining these findings.

13.
Am J Clin Nutr ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31826236

RESUMO

BACKGROUND: Maternal metabolic abnormalities have been related to offspring obesity especially during childhood. OBJECTIVES: We analyzed whether the gestational diabetes mellitus (GDM)-associated melatonin receptor 1B (MTNR1B) genotype of mothers modified the relation between maternal gestational weight gain and childhood obesity. METHODS: A total of 1114 Chinese mother-child pairs (mothers with or without prior GDM) were included. Mothers' MTNR1B rs10830962 genotype and gestational weight gain were assessed. Indicators of childhood obesity included BMI-for-age z-score, weight-for-age z-score, waist circumference, and body fat. Childhood overweight and obesity were also analyzed. RESULTS: We found that the maternal MTNR1B genotype significantly interacted with gestational weight gain on indicators of offspring's obesity (all P for interaction < 0.05). After multivariable adjustment, BMI-for-age z-scores associated with 1-kg gestational weight gain were 0.009 (SE 0.018), 0.026 (SE 0.010), and 0.061 (SE 0.010) in children with the maternal MTNR1B genotype CC, CG, and GG, respectively (P-interaction = 0.012). Similar interactions were observed for weight-for-age z-score, waist circumference, and body fat (P-interaction = 0.001, 0.003, and 0.012, respectively). The associations remained consistently significant in women with and without GDM. We also found significant interactions between the maternal MTNR1B genotype and gestational weight gain on the offspring's childhood overweight and obesity (P-interaction = 0.005 and 0.026, respectively). CONCLUSIONS: The maternal MTNR1B genotype might interact with gestational weight gain on offspring's obesity risk during childhood.

14.
BMJ Open Diabetes Res Care ; 7(1): e000774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798901

RESUMO

Objective: We aimed to investigate the association between maternal glycemic parameters and adverse pregnancy outcomes among high-risk pregnant women. Research design and methods: A total of 1976 high-risk pregnant women were enrolled between 2015 and 2017. All participants received a 75 g oral glucose tolerance test during the 24-30 gestational weeks and complete birth and delivery information was collected. Adverse pregnancy outcomes were defined as premature birth, birth weight >90th percentile, primary cesarean section, and pre-eclampsia. Logistic regression models were used to assess the association between five maternal glycemic parameters during pregnancy (fasting glucose, 1-hour glucose, 2-hour glucose, HbA1c, and serum 1,5-anhydroglucitol (1,5-AG)) and adverse pregnancy outcomes. Results: Of 1976 participants, 498 were diagnosed with gestational diabetes. The multivariable-adjusted ORs of adverse pregnancy outcomes for each one unit increase (1 mmol/L, 1%, or 1 µg/mL) were 2.32 (95% CI 1.85 to 2.92) for fasting glucose, 1.07 (95% CI 1.01 to 1.15) for 1-hour glucose, 1.03 (95% CI 0.96 to 1.10) for 2-hour glucose, 1.77 (95% CI 1.34 to 2.33) for HbA1c, and 0.96 (95% CI 0.94 to 0.98) for 1,5-AG, respectively. When all five glycemic parameters were simultaneously entered into the multivariable-adjusted model, only fasting glucose was significantly associated with total and individual adverse pregnancy outcomes. Receiver operating characteristic curve showed that fasting glucose plus any one of other four glycemic parameters had significantly enhanced the sensitivity of detecting adverse pregnancy outcomes. Conclusions: Fasting glucose at 24-30 gestational weeks was strongly associated with adverse pregnancy outcomes. Fasting glucose combined with one additional glycemic measurement showed non-inferiority indicating that post-load glycemic measurement was not necessary in detecting adverse pregnancy outcomes among high-risk pregnant women.

15.
BMC Med ; 17(1): 204, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31727112

RESUMO

BACKGROUND: Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. METHODS: Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. RESULTS: We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-ß2 (TGF-ß2)-TGF-ß type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-ß2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. CONCLUSIONS: These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

16.
Sci Rep ; 9(1): 17256, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754222

RESUMO

Cancer is a major cause of death worldwide, and an early diagnosis is required for a favorable prognosis. Histological examination is the gold standard for cancer identification; however, large amount of inter-observer variability exists in histological diagnosis. Numerous studies have shown cancer genesis is accompanied by an accumulation of harmful mutations, potentiating the identification of cancer based on genomic information. We have proposed a method, GDL (genome deep learning), to study the relationship between genomic variations and traits based on deep neural networks. We analyzed 6,083 samples' WES (Whole Exon Sequencing) mutations files from 12 cancer types obtained from the TCGA (The Cancer Genome Atlas) and 1,991 healthy samples' WES data from the 1000 Genomes project. We constructed 12 specific models to distinguish between certain type of cancer and healthy tissues, a total-specific model that can identify healthy and cancer tissues, and a mixture model to distinguish between all 12 types of cancer based on GDL. We demonstrate that the accuracy of specific, mixture and total specific model are 97.47%, 70.08% and 94.70% for cancer identification. We developed an efficient method for the identification of cancer based on genomic information that offers a new direction for disease diagnosis.

17.
Oncol Lett ; 18(5): 5490-5498, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612057

RESUMO

Isothiocyanates are a group of compounds that exist in the majority of cruciferous plants. A number of isothiocyanates have been demonstrated to exhibit anticancer effects; however, antitumor properties of propyl isothiocyanate (PITC) have not been evaluated previously. In this study, the possible effects of PITC on gastric cancer (GC) cells were investigated, and the potential underlying mechanisms were explored. The results demonstrated that PITC inhibited cell viability of two GC cell lines and induced cell cycle arrest and apoptosis. Treatment with PITC promoted total glutathione depletion in GC cell lines, leading to reactive oxygen species accumulation and DNA damage, which activated the mitochondria-dependent and p53 signaling pathways to trigger apoptosis in GC cells. The effects of PITC were reversed by N-Acetyl-L-cysteine. The results of the present study revealed the potential mechanisms of PITC on apoptosis induction in GC cells, which may be mediated by mitochondria-dependent apoptosis and DNA damage.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31616376

RESUMO

Objectives: Either maternal gestational diabetes mellitus (GDM) or hypertensive disorder of pregnancy (HDP) is associated with an increased risk of obesity in the offspring. However, their joint associations with obesity in offspring remain unclear. We investigated the joint associations of maternal GDM and HDP with childhood overweight in offspring. Methods: We performed a large study in 1967 mother-child pairs. Maternal GDM was diagnosed according to the 1999 World Health Organization (WHO) criteria. HDP was defined as self-reported doctor-diagnosed hypertension or treatment of hypertension (including gestational hypertension, preeclampsia, sever preeclampsia or eclampsia) after 20 weeks of gestation on the questionnaire. Body mass index (BMI) for age Z-score and childhood overweight were evaluated according to WHO growth reference. We used the general linear models to compare children's Z score for BMI and logistic regression models to estimate odds ratios of childhood overweight according to maternal different status of GDM and HDP. Results: Offspring of mothers with both GDM and HDP had a higher BMI for age Z-score (0.63 vs. 0.03, P < 0.001) than children born to normotensive and normoglycemic pregnancy. After adjustment for maternal and children's major confounding factors, joint GDM and HDP were associated with increased odds ratios of offspring's overweight compared with normotensive and normoglycemic pregnancy (2.97, 95% confidence intervals [CIs] 1.65-5.34) and GDM alone (2.06, 95% CIs 1.20-3.54), respectively. After additional adjustment for maternal pre-pregnancy BMI and gestational weight gain, joint maternal GDM, and HDP was still associated with an increased risk of offspring's overweight compared with the maternal normotensive, and normoglycemic group but became to have a borderline increased risk compared with the maternal GDM alone group. Conclusions: Maternal GDM alone or joint GDM and HDP were associated with increased ratios of offspring's overweight.

19.
Oncol Rep ; 42(6): 2345-2354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638254

RESUMO

Since the current methods of treatment for malignant glioma, radiotherapy and chemotherapy, are unsatisfactory, the development of novel therapeutic compounds is required. In the present study, the inhibitory effect of tetrandrine citrate (TetC) on the proliferation of human glioma U87 cells, as well as its mechanism of action, were investigated. An MTT assay was used to assess cell viability in vitro, and the production of intracellular reactive oxygen species (ROS) was determined by assessing the fluorescence intensity of 2,7­-dichlorofluorescein (DCF). Flow cytometry was used to determine the level of apoptosis and cell cycle status, and the protein expression levels of apoptosis­associated proteins were determined using western blotting. Additionally, the antitumor activity of TetC was assessed in vivo using a nude mouse xenograft model. The results revealed that in vitro, the proliferative rate of U87, U251 and human umbilical vein endothelial cells (HUVECs) was significantly reduced in a dose­dependent manner following treatment with TetC, although TetC had the greatest inhibitory effect on U87 cells. The vacuolization and apoptosis of U87 cells was induced using 10 and 20 µmol/l TetC, respectively. The overall proliferative inhibition was associated with an increase in the levels of ROS and apoptosis. In TetC­treated cells, the expression levels of apoptosis­related proteins, including cleaved (CL) caspase­3, Fas, phosphorylated (p)­p38 and p­JNK, were increased, whereas those of caspase­3 and Bcl­2 were decreased. In vivo, TetC was highly effective at inhibiting the growth of human glioma U87 xenografts in BALB/c nude mice, with a percentage growth inhibition of ≥68.7%. These findings indicated that the potent antitumor activity of TetC may be mediated through an increase in ROS levels, the downregulation of Bcl­2, and the upregulation of CL caspase­3, Fas, p­p38 and p­JNK expression levels.

20.
J Diabetes Complications ; 33(12): 107472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31653558

RESUMO

AIMS: The aim of the present study was to investigate the race-specific association between a history of gestational diabetes mellitus (GDM) and incidence of type 2 diabetes and evaluate how the risk changed over different years after delivery. METHODS: We performed two large cohorts - the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and the Tianjin GDM Observational Study. The multivariate cox regression model was used to assess the risk of incident postpartum diabetes between women with and without prior GDM. RESULTS: During a mean follow-up of 13.8 years, 405 women developed type 2 diabetes. After adjustment for multiple confounding factors, Chinese women with GDM had a higher risk of incident diabetes within 5 years postpartum than African Americans with GDM compared with Chinese and African Americans without GDM (Hazard ratio 71.5 in Chinese vs. 9.29 in African Americans). When the risk of incident diabetes was analyzed within 10 years, white women with GDM seemed to have a higher hazard ratio than African American and Chinese women with GDM compared with non-GDM women of different races. In comparison to African American women without GDM, the highest risk of type 2 diabetes over 10 years postpartum appeared in Chinese women with GDM, followed by African American women with GDM, and the smallest risk was seen in white women with GDM. CONCLUSIONS: Different genetic backgrounds and other risk factors among women of different races might contribute to the racial differences in the incidence of diabetes postpartum among women with GDM.

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