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1.
Prev Med ; 133: 106010, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027918

RESUMO

Few clinical trials have investigated lifestyle intervention effect on metabolic health in children. The study aimed to examine the effect of diet and physical activity intervention on the reduction of clustered metabolic risk score (CMRS) in children and moderators and mediators of the intervention effect. A multicentre, clustered randomised controlled trial was conducted with examination conducted at baseline and after intervention over one year. 7110 children (49.7% girls) with a mean of 9.06 (95% CI: 9.03, 9.09) years were included in the analysis. In Beijing, each three schools were randomly assigned to diet-only, physical activity-only intervention and control groups. In five other urban cities, each 15 schools were randomly assigned to comprehensive intervention and control groups. CMRS was computed by summing the Z scores of % fat mass, systolic blood pressure, fasting glucose, ratio of cholesterol to high-density lipoprotein, and triglyceride. Compared with controls (n = 2808), children in the comprehensive intervention group (n = 2848) had more reduction in CMRS (multivariate-adjusted mean difference (95% CI): -0.49 (-0.85, -0.14)). The body mass index (BMI) reduction explained 7.3% (95% CI 2.8%-18.1%) of the total intervention effect. The intervention was more effective in children with higher birthweight, lower parental BMI, or complete parental data. Diet-only or physical activity-only intervention had non-significant effects on CMRS reduction. Our multidimensional comprehensive intervention resulted in significant reduction in CMRS in primary school children and this effect was modified by birthweight, parental BMI, and parental involvement. A minority of metabolic risk reduction was mediated through BMI. Clinical Trial Registry number and website: ChiCTR-PRC-09000402, URL: http://www.chictr.org.cn.

2.
Reprod Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046374

RESUMO

Diminished ovarian reserve (DOR) is characterized by the depletion of the ovarian pool, which leads to reductions in oocyte quality and quantity. Studies have suggested that ovarian reserve or ovarian aging is tightly related to apoptosis. However, the cell death mechanism is not comprehensively understood. Parthanatos, a type of poly [ADP-ribose] polymerase 1(PARP1)-dependent and apoptosis-inducing factor (AIF)-mediated cell death, plays a crucial role in various disorders. In the present study, we aimed to investigate whether parthanatos is involved in the pathogenesis of DOR. We recruited 40 patients (20 DOR patients and 20 normal ovarian reserve (NOR) patients) and examined PAR expression and AIF translocation in their isolated cumulus GCs (granulosa cells) by fluorescence microscopy. Our results demonstrated that PAR expression and AIF nuclear translocation were significantly higher in cumulus GCs of DOR patients, suggesting that PARP1-dependent cell death may be associated with DOR pathophysiology. Moreover, we tested the protective function of melatonin on hydrogen peroxide (H2O2)-induced parthanatos in human ovarian cancer (IGROV1) cells. Our results demonstrated that H2O2 treatment of IGROV1 cells led to excessive protein PARylation and AIF translocation into the nuclei. Melatonin effectively inhibits PARylation, blocks translocation of AIF into the nucleus, and consequently decreases the risk of parthanatos in cumulus GCs.

3.
Reprod Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046395

RESUMO

Epithelial-mesenchymal transition (EMT) induced by estrogen contributes to the development of adenomyosis. However, the exact underlying mechanism remains mostly obscure. We hypothesized that a transmembrane glycoprotein neuropilin 1 (NRP1) was critical in the EMT induced by estrogen, accelerating the development of adenomyosis. We firstly investigated the expression pattern of NRP1 in endometrium samples from women with adenomyosis. We found that NRP1 expression was significantly increased in the endometrium of uterine adenomyosis, especially in the ectopic endometrium. To determine the role of NRP1 in the EMT in endometrial cells, we used an NRP1 overexpression retrovirus to up-regulate the NPR1 expression in human endometrial cells (HEC-1-A). Endometrial cells infected with NRP1 retroviruses showed a high expression of NRP1 and exerted a mesenchymal phenotype, characterized by down-regulation of E-cadherin and Occludin, up-regulation of α-SMA and N-cadherin, and enhanced migration. Then, we found that 17ß-estradiol (E2) up-regulated the expression of NRP1 in endometrial cells in a dose-dependent manner, which was eliminated by raloxifene, a selective estrogen receptor inhibitor. Importantly, NRP1 shRNA significantly suppressed the EMT induced by E2 in endometrial cells. And NRP1 shRNA significantly inhibited the phosphorylation of Smad3 and restored the expressions of Slug and Snail1 mRNA. Collectively, these data highlight the possible role of NRP1 in the EMT in the development of adenomyosis and provide a potential therapeutic target for adenomyosis patients.

4.
Am J Clin Nutr ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020162

RESUMO

BACKGROUND: Current evidence on associations between intakes of linoleic acid (LA), the predominant n-6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis. OBJECTIVE: The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality. METHODS: We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis. RESULTS: Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I2 = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I2 = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I2 = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I2 = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I2 = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I2 = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality. CONCLUSIONS: In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

5.
Oncogene ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034306

RESUMO

Cancer metabolism research has recently been revived and its focus expanded from glucose and the Warburg's effects on other nutrients, such as glutamine. The underlying mechanism of oncogenic alterations of glutaminolysis remains unclear. Genetic alterations of EGFR are observed in ~50% of glioblastoma (GBM) patients, and have been found to play important roles in the metabolic abnormalities of GBM. In this study, we found that glutamine metabolism was upregulated after EGFR activation in a GDH1 (glutamate dehydrogenase 1)-dependent manner. Knockdown of GDH1 significantly reduced the cell proliferation, colony formation and tumorigenesis abilities of glioblastoma cells. Furthermore, we showed that GDH1-mediated glutaminolysis was involved in EGF-promoted cell proliferation. EGFR triggered the phosphorylation of ELK1 at Ser 383 through activating MEK/ERK signaling. Phosphorylated ELK1 enriched in the promoter of GDH1 to activate the transcription of GDH1, which then promoted glutamine metabolism. In addition, EGFR activation did not accelerate glutaminolysis in ELK1 knockdown or ELK1 Ser383-mutated cells. Collectively, our findings indicate that EGFR phosphorylates ELK1 to activate GDH1 transcription and glutaminolysis through MEK/ERK pathway, providing new insight into oncogenic alterations of glutamine metabolism.

6.
J Sep Sci ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052934

RESUMO

A method for determining amitraz and 2,4-dimethylaniline in honey was established by using ultra-HPLC and Q Exactive after applying quick, easy, cheap, effective, rugged, and safe [2] extracting process. A suitable extraction method was designed to extract the amitraz and 2,4-dimethylaniline after a suitable amount of honey samples was dissolved. A Thermo Syncronis C18 column (100 × 2.1 mm, 1.7 µm) was used for chromatographic separation of the samples. Then the two compounds were quantitatively analyzed via a program of Q Exactive. The linearity of amitraz and 2,4-dimethylaniline was good in the concentration range of 0.5 µg/L to 100 µg/L, and the correlation coefficient R2 was greater than 0.99. The average recovery and relative standard deviation of each component were 81.3%-90.0% and 5.1%-7.2%. The 24- and 48-hour test results showed that the sample needed to be tested within 24 hours. The limit of detection was 0.1 µg/kg for amitraz and 2,4-dimethylaniline, whereas the limit of quantitation was 0.3 µg/kg for both. This article is protected by copyright. All rights reserved.

7.
BMJ ; 368: l6669, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915124

RESUMO

OBJECTIVE: To examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: The Nurses' Health Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366). MAIN EXPOSURES: Five low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%). MAIN OUTCOME: Life expectancy free of diabetes, cardiovascular diseases, and cancer. RESULTS: The life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50. CONCLUSION: Adherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estilo de Vida Saudável/fisiologia , Expectativa de Vida , Neoplasias , Comportamento de Redução do Risco , Adulto , Consumo de Bebidas Alcoólicas , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/psicologia , Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Neoplasias/psicologia , Pesquisa em Enfermagem , Estudos Prospectivos , Fumar
8.
J Control Release ; 320: 32-44, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931051

RESUMO

Renal fibrosis often occurs in chronic kidney disease, and effective treatment is needed. Celastrol (CEL) may attenuate renal fibrosis, but it distributes throughout the body, leading to severe systemic toxicities. Here we designed a system to deliver CEL specifically to interstitial myofibroblasts, which is a key driver of renal fibrogenesis. Fibronectin is highly expressed in fibrotic kidney. The pentapeptide CREKA, which specifically binds fibronectin, was conjugated to PEGylated liposomes (CREKA-Lip). CREKA-coupled liposomes significantly increased the uptake of unmodified liposomes by activated NRK-49F renal fibroblasts. Systemic administration of CREKA-Lip to mice led to their accumulation in fibrotic kidney, where they were specifically internalized by interstitial myofibroblasts. Loading CEL into CREKA-Lip effectively inhibited the activation and proliferation of NRK-49F cells in vitro, and they markedly alleviated renal fibrosis, injury and inflammation induced by unilateral ureteral obstruction in mice. Besides, CEL-loaded CREKA-Lip was associated with significantly lower toxicity to major organs than free CEL. These results suggest that encapsulating CEL in CREKA-Lip can increase its therapeutic efficacy and reduce its systemic toxicity as a potential treatment for renal fibrosis.

9.
Bioorg Med Chem Lett ; 30(4): 126906, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31902708

RESUMO

The prevalence of Zika virus (ZIKV) has become widespread in recent years. ZIKV infection is associated with severe congenital CNS malformations in both newborns and adults. However, neither vaccines nor therapeutics are available to control ZIKV infection until now. We started by hit screening our in-house small molecule library, then designed, synthesized, and evaluated a new class of 1, 4-bibenzylsubstituted piperazine derivatives for their cytopathic effect (CPE) protection effect in a ZIKV-infected Vero E6 cellular assay. A preliminary structure-activity relationship study identified five novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile analogs with obvious CPE reduction effects against ZIKV at micromolar concentrations. Moreover, compound 3p exerted a significant antiviral effect on both Zika RNA replication and virus protein expression in a dose-dependent manner at low micromolar concentrations. This study demonstrated the potential of a novel 4-amino-2-(4-benzylpiperazin-1-yl)methylbenzonitrile scaffold for the development of anti-ZIKV candidates.

10.
J Agric Food Chem ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31976658

RESUMO

Various mycotoxins widely co-exist in agro-products, and their combined effects cause toxicity and potential carcinogenicity to humans and animals. In this work, we developed an economical and sensitive quantum dots (QDs)/QD microbead (QDs/QB)-based multiplex immunochromatographic assay (mICA) for the rapid detection of fumonisin B1 (FB1), zearalenone (ZEN), and ochratoxin A (OTA) without the building-up process of mycotoxin conjugates. QDs and QBs were selected as fluorescent reporters and conjugated with antimycotoxin monoclonal antibodies for improving sensitivity. Furthermore, phage-displayed FB1, ZEN, and OTA mimotope peptide-based soluble and monovalent fusions to maltose-binding protein (MBP) were applied onto the test line of the mICA as the mimetic coating antigen. Under the optimized conditions, the visual detection limits (vLODs) of peptide-MBP-based mICA could be obtained as 0.25 ng/mL for FB1, 3.0 ng/mL for ZEN, and 0.5 ng/mL for OTA within 10 min. The results for spiked real sample detection indicate good accuracy, reproducibility, and practicability. In addition, the proposed mICA was comparable with ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in terms of reliability in detecting FB1, ZEN, and OTA using natural samples. From the point of promoting commercial production, these time-saving and low-cost peptide-MBP antigens applied in ICA might provide promising potential for promoting productivity and decreasing the cost of production.

11.
Meat Sci ; 162: 108043, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31911339

RESUMO

In order to study the potential of replacing pork back-fat by sodium alginate solution (sodium alginate/water = 1/29, W/W), the physico-chemical, protein conformation and sensory of frankfurters made with various amounts of pork back-fat and sodium alginate were evaluated. With the increase of sodium alginate solute, the fat and energy was decreased significantly (P < .05). Compared with the control, the cooking yield, emulsion stability, L⁎ and ΔE values were not different significantly (P > .05) when pork back-fat was replaced by 25% and 50%, meanwhile, a decrease of α-helix content accompanied by an increase of ß-sheet, ß-turn and random coil content, more hydrophobic and tyrosine residues became exposed, those implied the hardness was increased. The texture, juiciness and overall acceptance scores were decreased significantly (P < .05) when pork back-fat was replaced beyond 50%. From the above, the use of sodium alginate solution instead of pork back-fat could transform protein structure and lowered fat and energy of frankfurters.

12.
J Periodontol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950502

RESUMO

BACKGROUND: The anti-inflammatory effect associated with flavonoids containing foods and beverages could potentially impact the risk of periodontal disease. We prospectively investigate the associations between habitual flavonoid intake and incidence of periodontitis. METHODS: The study population was 34,940 men from the Health Professionals Follow-Up Study, who were healthy and free of periodontal disease at baseline (1986). Participants in the study provided medical and dental history through mailed questionnaires biennially, and provided dietary data through semi-quantitative food frequency questionnaires every 4 years. We examined the associations between total flavonoids and six flavonoid subclasses (flavonoid polymers, anthocyanins, flavan-3-ols, flavanones, flavones, and flavonols) and incidence of periodontitis using Cox proportional hazard models. We adjusted for age, smoking, body mass index, physical activity, alcohol consumption, Alternative Healthy Eating Index, and diabetes. RESULTS: There was no association between total flavonoids and the risk of periodontitis. The hazard ratio comparing the highest quintile of total flavonoid to the lowest quintile was 0.97 (95% confidence interval: 0.87 to 1.08, P-value for trend = 0.61). Similar comparisons for flavonoids subclasses also did not show significant associations. CONCLUSION: No association was detected between habitual flavonoid intake and risk of periodontitis in the study population.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31948761

RESUMO

Telmisartan is a known angiotensin II (Ang II) AT1 receptor blocker (ARB). While the beneficial effect of Telmisartan on glucose and lipid metabolism has been reported, the underlying molecular mechanism remained unclear. The endoplasmic reticulum (ER) stress is considered as one of important factors contributing to insulin resistance. In this study, we found that Telmisartan alleviated diet-induced obesity and insulin resistance, suppressed inflammation in adipose tissue, and alleviated hepatic steatosis. Furthermore, we showed that Telmisartan suppressed ER stress by activating AMP-activated protein kinase (AMPK) signaling pathway in vivo. In differentiated 3T3-L1 adipocytes, Telmisartan also improved palmitate acid (PA) induced ER stress. Compound C, an AMPK inhibitor, could abolish beneficial effect of Telmisartan on ER stress. Our data indicated Telmisartan improved obesity-induced insulin resistance through suppression of ER stress by activation of AMPK. These results provided the evidence that Telmisartan may have therapeutic potential for the treatment of obesity and type II diabetes.

14.
Medicine (Baltimore) ; 98(50): e18403, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852159

RESUMO

Studies have shown that forkhead/winged helix transcription factor P3 (FOXP3) tumor infiltrating lymphocytes (TILs) are intimately associated with invasion and survival of many invasive tumors. The inflammatory chemokine ligand 20 (CCL20) and its receptor CCR6 were found to be associated with tumor prognosis in some studies. Although increases in FOXP3 TILs infiltration and CCL20 expression have been revealed in several malignancies, their correlation in human breast tumors is as yet unclear.Surgically resected samples from 156 patients with invasive breast cancer (BC) were assessed for the expression of FOXP3 and CCL20 by immunohistochemistry. Correlation between their expressions and the association with clinicopathological characteristics and patient's prognosis were studied. Forty pairs of fresh BC and their nontumor adjacent tissues (NATs) in BC were carried out by real-time quantitative PCR (qRT-PCR) to evaluate the correlation between FOXP3 and CCL20 mRNA expression.CCL20 and FOXP3 TILs mRNA expression in tumor tissue demonstrated a high correlation (rs = 0.359, P < .001) in this cohort of breast cancer patients. Both elevated CCL20 expression and FOXP3 TILs infiltration were significantly correlated with high histological grade, positive human epidermal growth factor receptor-2 (HER2), high Ki67 index, and axillary lymph node metastases. Tumors with concomitant high expressions of both markers had the worst prognosis. Multivariate analysis showed that these 2 markers were independent predictors of overall survival. The patients with axillary lymph node metastases with the concomitant CCL20 high expression and increased FOXP3 TILs infiltration had the worst overall survival (OS) (P < .001), In lymph node-negative breast cancer patients, the status of CCL20 and FOXP3 was not related to OS (P = .22).The results suggest that CCL20 and FOXP3 TILs may have synergistic effects, and their upregulated expressions may lead to immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming at blocking CCL20 and depleting FOXP3 might improve therapeutic efficacy in breast cancer patients.


Assuntos
Carcinoma de Mama in situ/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Quimiocina CCL20/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Adulto , Biomarcadores Tumorais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
ACS Omega ; 4(21): 19128-19135, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31763535

RESUMO

Poly(oxymethylene) dimethyl ethers (PODME n , n = 2-6) are novel oxygenated compounds that can be used as promising candidates for new-generation fuels because of their excellent combustion performance. The oxidation of PODME n (n = 2-6) is essential for the understanding of the combustion process. It is necessary to study the relationship between kinetic parameters and cetane number (CN) of PODME n (n = 2-6). In order to predict initiation step rate constants for the oxidation of PODME n (n = 2-6), quantum mechanical calculations are performed using M06-2X/6-311G(d,p) and B3LYP/6-311G(d,p) methods. Structural, energetic, thermodynamics, and kinetics of the automatic ignition process are assessed. The kinetic model based on the conventional transition state theory is used to calculate the initiation step reaction rate constants at 1000 K. In both M06-2X/6-311G(d,p) and B3LYP/6-311G(d,p) methods, the calculated rate constants of the hydrogen abstraction process have an excellent correlation with the experimental CN of PODME n (n = 2-6). Our methodology presented here can be used to simulate chemical kinetics for other fuel additives.

16.
Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756480

RESUMO

Sesbania gum (SG) was successfully modified by combining cross-linking with hydroxypropylation in solvent of ethanol. The hydroxypropylation technology parameters were optimized by the orthogonal test. The results indicated that both cross-linking and hydroxypropylation could improve the freeze-thaw stability, acid and alkali resistance of SG. After the cross-linking and hydroxypropylation of SG, the retrogradation was evidently strengthened. The surfaces of SG derivatives such as cross-linked sesbania gum (CLSG) and hydroxypropyl cross-linked sesbania gum (HCLSG) particles also became very rough, compared with SG. The sequence combination of first cross-linking and then hydroxypropylation was helpful to the follow-up hydroxypropylation of SG. The cross-linking and hydroxypropylation resulted in an obvious reduction in the melting enthalpy of SG, which belonged to a semicrystalline polymer. The cross-linking and hydroxypropylation influenced the thermal properties, and destroyed the crystalline regions of SG. According to SEM, the hydroxypropylation has greater contribution to the destruction than cross-linking. Both cross-linking and hydroxypropylation gave rise to the expansion of SG grains, but the swelling manner was different each other.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31750895

RESUMO

BACKGROUND: To examine the impact of combined lifestyle factors on premature mortality and life expectancy in Chinese adults. METHODS: A total of 44,052 Chinese adults aged 45 to 74 years free of cardiovascular disease (CVD), cancer, and diabetes were followed from recruitment (1993-1998) to the end of 2016 in the Singapore Chinese Health Study. A composite score (0-5 scale) was calculated based on five baseline healthy lifestyle factors including healthy diet, non-smoking status, light to moderate alcohol drinking, being physically active and optimal body mass index. Mortality cases were identified through linkage with the nationwide death registry. RESULTS: Adopting five healthy versus none was associated with a lower risk of all-cause and cause-specific mortality, and the hazard ratio (95% confidence interval) was 0.38 (0.29, 0.51) for all-cause mortality, 0.26 (0.13, 0.52) for CVD mortality, and 0.59 (0.37, 0.92) for cancer mortality. Non-adherence to 4-5 healthy lifestyle factors accounted for 34.9% (95% confidence interval: 29.2, 40.2) in population attributable fraction for all-cause mortality, 35.1% (23.7, 44.9) for CVD mortality, and 18.0% (6.5, 28.0) for cancer mortality. Conversely, adherence to 4-5 healthy lifestyle factors versus none could achieve a gain of 8.1 years in women and 6.6 years in men for the life expectancy at 50 years. CONCLUSIONS: A healthier lifestyle is associated with a substantially reduced risk of mortality and a longer life expectancy in the Chinese population. Our findings highlight the necessity of coordinated actions targeting combined lifestyle factors in reducing the overall burden of diseases and premature deaths.

18.
Reproduction ; 158(6): 493-501, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671404

RESUMO

Uterine peristalsis plays a vital role in fertility and female reproductive health. Although uterine peristalsis is thought to be correlated with some hormones and uterine pathologies, the physiological mechanisms underlying uterine peristalsis remain not quite clear. This study aimed to identify changes in miRNA in the endometrium of patients with abnormally high-frequency (hyper-) and low-frequency (hypo-) peristalsis to clarify whether miRNAs regulate uterine peristalsis. We used a miRNA microarray and RT-qPCR to identify changes in miRNA in endometrial tissue, a collagen gel contraction assay on co-cultured human endometrial stromal cells (ESCs) to analyze how the altered regulation of miRNAs influences uterine smooth muscle (USM) contraction, Western blots and other assays to elucidate the potential mechanisms involved. We found that among several differentially regulated miRNAs, miR-29c-3p was overexpressed in endometrial samples from patients with hypoperistalsis; oxytocin receptor (OXTR) expression was low in endometrial samples from patients with hypoperistalsis. Bioinformatic analysis and luciferase assays indicated that OXTR is a target of miR-29c-3p, which attenuates its expression. Additionally, downregulation of miR-29c-3p in ESC cultures increased the expression of aldo-keto reductase family 1, member C3 (AKR1C3) and increased the release of prostaglandin F2 alpha (PGF2α). Co-cultured ESCs overexpressing miR-29c-3p reduced USM cell contractions; the opposite tendency was found when ESCs were transfected with a miR-29c-3p inhibitor. To conclude, miR-29c-3p in endometrial cells regulates uterine contractility by attenuating the expression of OXTR and reducing PGF2α release.

19.
BMC Med Genet ; 20(1): 183, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727004

RESUMO

BACKGROUND: It is well established that long-term use of aspirin can cause gastric mucosal injury. ACEIs and ARBs are inversely related to gastric ulcer development. This study aimed to evaluate the relationship between SLCO1B1 polymorphisms, which can affect ACEI and ARB transport, and gastric mucosal erosion in elderly male Chinese patients with cardiovascular disease who use aspirin. METHODS: Patients taking aspirin and an ACEI or ARB concomitantly who had undergone endoscopic screening for gastric erosion were analyzed for SLCO1B1 polymorphisms by a TaqMan assay. RESULTS: The frequency of the SLCO1B1*1b/*1b diplotype (42% vs. 24%; p = 0.002) was significantly higher in the gastric mucosal erosion group than in the control group. After adjustment for significant factors, SLCO1B1*1b/*1b (OR, 2.64; 95% CI, 1.59-4.17; p < 0.05) was found to be associated with gastric mucosal erosion in aspirin users. CONCLUSIONS: The presence of the SLCO1B1*1b/*1b diplotype may be a risk factor for aspirin-induced gastric mucosal erosion in elderly Chinese men taking aspirin and an ACEI or ARB concomitantly.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31669281

RESUMO

In this study, a Streptomyces strain was isolated from the soil samples of Yanghu Wetland Park in Changsha, Hunan Province. This strain showed excellent antimicrobial activity against 10 fish pathogens, as indicated by the results of the agar-diffusion and oxford cup assays. After 16s rDNA sequencing and physiological & biochemical analyses, it was identified as Streptomyces amritsarensis, namely for S. amritsarensis N1-32. Cytotoxicity test was performed, and the results exhibited that this strain had no toxicity to hepatic L8824 cell line from grass carp liver. The diets supplemented strain N1-32 at concentrations of 1 × 107 cfu/g and 1 × 109 cfu/g was used to feed fish. After 28 days, the expression levels of antioxidant-related genes Nrf2 and Keap1 in the liver and spleen were significantly up-regulated, and the expression of immune-related gene IgM was notably increased in the liver, kidney, head-kidney, and spleen. Toll-like receptor 4 (TLR4) gene expression was up-regulated in the spleen, and TLR4, myeloid differentiation factor 88 (MyD88) gene were up-regulated in the kidney. The survival rate of grass carp was significantly improved after pathogen infection. Whole-genome analysis of N1-32 showed that the strain harbored related genes, capability for producing substances that enhance the immunity of grass carp and inhibit pathogens. A total of 22 gene clusters were identified in the genome, including 5 terpene gene clusters, 4 nonribosomal peptide-synthetase (NRPS) gene clusters and 2 lantipeptide gene clusters. In summary, these results showed that strain N1-32 as a feed additive could regulate grass carp immunity and enhance the resistance of grass carp against fish pathogens.

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