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1.
Artigo em Inglês | MEDLINE | ID: mdl-31666189

RESUMO

Iron accumulation has been frequently found in atherosclerotic lesions, especially in macrophages/foam cells, but the exact mechanisms by which hepcidin induces iron retention in plaque macrophages and its roles in atherogenesis remain unknown. Double immunofluorescence staining showed colocalization of hepcidin-positive macrophages with ox-LDL, TLR4, p-p65 and ferritin light chain (ferritin-L) both in human and murine atherosclerotic lesions. RAW264.7 macrophages incubated with ox-LDL showed elevated expression of TLR4, p-p65, hepcidin, ferritin-L/H, CYP27A1, CD36, PPARγ, liver X receptor α (LXRα), and ATP binding cassette transporter A1/G1 (ABCA1/G1), as well as increased intracellular labile iron pool level and lipid accumulation. Ox-LDL-induced iron retention and lipid accumulation were aggravated by lipopolysaccharide but blocked by TAK-242, an antagonist of TLR4. Moreover, macrophage TLR4/NF-κB pathway activation and foaming triggered by ox-LDL was enhanced by ferric ammonium citrate or exogenous hepcidin but attenuated by hepcidin silencing or the use of iron chelator. Meanwhile, the addition of hepcidin stimulated CD36-mediated Dil-labeled-ox-LDL uptake and inhibited the LXRα-ABCA1/G1 pathway-dependent cholesterol efflux in macrophages, which was significantly reversed by 27-hydroxycholesterol but further exacerbated by cyclosporin A, a selective inhibitor of CYP27A1. Our study provided the evidence that iron trapped in atherosclerosis plaque macrophages contributes to cholesterol disequilibrium-initiated foam cell formation, which is provoked by the unique but largely unknown autocrine formation of hepcidin in plaque macrophages via activating the TLR4/NF-κB pathway when exposed to ox-LDL. Such findings, considering the intricate vicious cycle between macrophage hepcidin autocrine-triggered iron retention and cholesterol disequilibrium, may shed new light on the "iron hypothesis" of atherosclerosis.

2.
J Diabetes Investig ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661606

RESUMO

AIMS/INTRODUCTION: Elevated serum cancer antigen 19-9(CA19-9) levels have been found in diabetes patients in most observational studies; however, whether there is causal association between CA19-9 and diabetes mellitus (DM) is unclear. MATERIALS AND METHODS: Our study was conducted based on the Dongfeng-Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19-9 levels and incident DM risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19-9 and DM risk in a cross-sectional study (3,349 DM cases and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score (GRS) was calculated by adding the CA19-9 increasing alleles in five SNPs (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2) which were identified in previous genome-wide association study on serum CA19-9 levels. RESULTS: In the prospective study, a total of 1,004 incident DM cases were diagnosed during mean 4.54 years of follow-up period. Elevated serum CA19-9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a HR of 1.20 (95% CI: 1.11, 1.30) per SD (12.17U/ml) CA19-9 increased. Using the genetic score to estimate the unconfounded effect, we did not find causal association of CA19-9 with diabetes risk (OR per weighted CA19-9-increasing allele: 0.99; 95 % CI: 0.94-1.04; P=0.61). CONCLUSIONS: The present study does not support a causal association of serum CA19-9 with diabetes risk. CA19-9 might be a potential biomarker of incident DM risk.

3.
Brachytherapy ; 18(5): 733-739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31515049

RESUMO

INTRODUCTION: To evaluate the feasibility and safety of ultrasound-guided iodine-125 interstitial implants for high-risk hepatocellular carcinoma. METHODS: From October, 2016, to August, 2018, 49 patients suffering from a total of 66 hepatocellular carcinoma lesions were treated with ultrasound-guided iodine-125 interstitial implantation. Treatment planning system was applied to make preoperative plan. The response evaluation criteria in solid tumors were used to evaluate the curative effect. The evaluated outcomes included postoperative complications and complete disease control rate, 6-month disease-free survival, and 6-month overall survival. RESULTS: All 49 patients underwent iodine-125 seed implantation successfully. Patients were followed up for 5 to 27.5 months. No patients developed serious complications and only 2 (4.1%) patients had slight pain. The complete response was seen in 21 lesions (31.8%), partial response in 26 lesions (39.4%), stable disease in eight lesions (12.1%), and progressive disease in 11 lesions (16.7%). The overall disease control rate was reached to 83.3%. The 6-month disease-free survival rate was 46.4% with a median disease-free survival time of 5.0 months. The 6-month overall survival rate was 83.6% with a median overall survival time of 15.0 months. CONCLUSIONS: Iodine-125 interstitial implantation is a kind of safe and feasible treatment for high-risk hepatocellular carcinoma.

4.
Int J Mol Sci ; 20(19)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547176

RESUMO

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP's curative effect on hearing loss and neuronal damage in noise-exposed mice.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31340440

RESUMO

Previous studies of the relationship between job security and job satisfaction were mostly conducted on research samples in Asia from the perspective of oriental culture; however, under the same cultural background, different social systems might lead to different cognition outcomes. Therefore, this study examines the job security and organizational support of Taiwan and mainland China employees from the perspectives of competence enhancement motivation, and investigates the relationship between employability and job satisfaction. Adopting judgmental sampling, a total of 1307 valid questionnaires were collected from Taiwan and mainland China employees. The path relationship of the two groups was examined through structural equation modeling (SEM) by using analysis of moment structure (AMOS). Results show that job security and organizational support are positive for employability and job satisfaction. Employability has a positive influence on job satisfaction. Additionally, employability has a mediating effect of job security and organizational support on job satisfaction.

6.
Hypertension ; 74(3): 660-668, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352830

RESUMO

Increased short-term blood pressure (BP) variability is associated with adverse cardiovascular outcomes in patients with hypertension. The present study investigated the long-term prognostic significance of the short-term blood pressure variability in patients on hemodialysis. A total of 149 patients (53.0% male; mean age: 54.5±15.1 years) receiving regular hemodialysis for >6 months were enrolled. They completed a 44-hour (excluding the hemodialysis session) ambulatory BP monitoring and comprehensive hemodynamic assessments, including carotid-femoral pulse wave velocity and pressure waveform decomposition (forward and backward wave amplitude). Blood pressure variability parameters, including average real variability (ARV) of systolic BP, diastolic BP, and pulse pressure (ARVp) during daytime, nighttime, and overall 44 hours were calculated. During a median follow-up of 14 years, 78 deaths (52.4%) were confirmed. In multivariable Cox regression analysis, none of the ambulatory BP parameters were predictive of mortality. In contrast, nighttime ARVp was consistently and significantly associated with all-cause mortality in multivariable Cox models adjusting for age, sex, albumin, hemodialysis treatment adequacy, and 44-hour systolic BP (continuous variable analysis, per 1-SD, hazard ratio=1.348; 95% CI, 1.029-1.767; categorical variable analysis, ≥8.5 versus <8.5 mm Hg; hazard ratio=1.825; 95% CI, 1.074-3.103). Forward wave amplitude and 44-hour systolic BP were identified as the 2 most important determinants of nighttime ARVp. Addition of nighttime ARVp to the base model significantly improved prediction of all-cause mortality (Net reclassification improvement =0.198; P=0.0012). In hemodialysis patients, increased short-term nighttime pulse pressure variability but not ambulatory BP levels were significantly predictive of long-term all-cause mortality.

7.
Vaccine ; 37(36): 5341-5349, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31351798

RESUMO

A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation.

8.
Diabetes Metab Res Rev ; : e3202, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291052

RESUMO

BACKGROUND: We examined the association between metabolically healthy obese (MHO) and diabetes incidence in a middle-aged and elderly population and whether the association differed by the presence of nonalcoholic fatty liver disease (NAFLD). METHODS: We examined 17 801 participants without diabetes at study entry (7980 males and 9821 females with a mean age of 63.2 years) derived from the Dongfeng-Tongji cohort study (median follow-up: 4.6 years). Participants were divided into six groups based on BMI (normal weight, overweight, or obese) and metabolic health (healthy/unhealthy) defined by the Adult Treatment Panel III criteria. The MHO was defined as BMI greater than 28.0 kg/m2 with 0 or 1 of four metabolic abnormalities (elevated blood pressure, triglyceridaemia, hyperglycaemia, low HDL cholesterol). The hazard ratio (HR) and 95% confidence interval (CI) for incident diabetes were derived from the Cox proportional hazard regression model. RESULTS: During 79 843 person-years of follow-up, 1453 individuals developed diabetes. Compared with metabolically healthy normal weight (MH-NW) individuals, the multivariable-adjusted HRs (95% CI) were 1.74 (1.16-2.59) for MHO and 2.15 (1.65-2.81) for metabolically unhealthy obese subjects after adjusting for age, sex, smoking, alcohol drinking, physical activity, fruit and vegetable consumption, family history of diabetes, fasting glucose, waist circumference, and NAFLD. Among those without NAFLD, MHO individuals showed higher incidence of diabetes (multivariate-adjusted HR = 2.71, 95% CI: 1.47-5.00) than MH-NW individuals. CONCLUSIONS: The MHO phenotype was associated with increased incidence of diabetes in a middle-aged and elderly population, and the association did not differ by the presence or absence of NAFLD.

9.
Neurosci Lett ; 707: 134308, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31153972

RESUMO

Acori Tatarinowii Rhizoma (ATR, the dried rhizome of Acorus tatarinowii Schott.) is a traditional Chinese medicine widely used to treat brain diseases, e.g. depression, forgetfulness, anxiety and epilepsy. Several lines of evidence support that ATR has neuronal beneficial functions in animal models, but its action mechanism in cellular level is unknown. Here, we identified α-asarone and ß-asarone could be the major active ingredients of ATR, which, when applied onto cultured rat astrocytes, significantly stimulated the expression and secretion of neurotrophic factors, i.e. nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF), in dose-dependent manners. These results suggested that the neuronal action of ATR, triggered by asarone, might be mediated by an increase of expression of neurotrophic factors in astrocytes, which therefore could support the clinical usage of ATR. In addition, application of PKA inhibitor, H89, in cultured astrocytes partially blocked the asarone-induced neurotrophic factor expression, suggesting the involvement of PKA signaling. The results proposed that α-asarone and ß-asarone from ATR could serve as potential candidates for drug development in neurodegenerative diseases.

10.
Environ Int ; 129: 497-506, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158596

RESUMO

BACKGROUND: Metals exposure from natural environment and pollution have been linked to cardiovascular disease (CVD). However, whether associations existing between plasma multiple metals and incident cardiovascular disease in patients with type 2 diabetes (T2D) is unknown. OBJECTIVES: We conducted a prospective cohort study to investigate whether plasma levels of metals are associated with incident CVD risk in patients with T2D. METHODS: In a prospective study of 3897 type 2 diabetes embedded in the Dongfeng-Tongji cohort, fasting blood samples were collected in 2008 at baseline and in 2013 in the first follow-up period. Plasma concentrations of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations between plasma metal concentrations and CVD risk in patients with T2D were investigated with Cox proportional hazards models. RESULTS: During an average of 6.2 years follow-up, 1114 participants developed CVD. In the single-metal models adjusting for established cardiovascular risk factors, plasma zinc and selenium levels were negatively and strontium was positively associated with incident CVD risk in patients with T2D. Similar results were obtained in the multiple-metal model, the HRs (95% CIs) for zinc, selenium, and strontium comparing extreme quartiles were 0.78 (95% CI: 0.65-0.93; P trend = 0.011), 0.76 (95% CI: 0.64-0.91; P trend = 0.001), and 1.51 (95% CI: 1.26-1.81; P trend <0.001), respectively. In the joint association analyses of two metals, individuals with high plasma levels of zinc and selenium had significantly lower risk of incident CVD in patients with T2D than those with low levels (HR = 0.77, 95% CI: 0.65-0.91). CONCLUSIONS: The present study suggested that plasma levels of zinc and selenium had an inverse association with incident CVD risk in patients with T2D, while strontium had a positive correlation. Plasma zinc and selenium combinedly decreased incident CVD risk in patients with T2D. Further research is still needed to verify these findings in other populations.

11.
Curr Med Sci ; 39(3): 483-492, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209822

RESUMO

The intervention of behaviors, including physical activity (PA), has become a strategy for many hospitals dealing with patients with chronic diseases. Given the limited evidence available about PA and healthcare use with chronic diseases, this study explored the association between different levels of PA and annual hospital service use and expenditure for inpatients with coronary heart disease (CHD) in China. We analyzed PA information from the first follow-up survey (2013) of the Dongfeng-Tongji cohort study of 1460 CHD inpatients. We examined factors such as PA exercise volume and years of PA and their associations with the number of inpatient visits, number of hospital days, and inpatient costs and total medical costs. We found that the number of hospital days and the number of inpatient visits were negatively associated with intensity of PA level. Similarly, total inpatient and outpatient costs declined when the PA exercise volume levels increased. Furthermore, there were also significant associations between the number of hospital days, inpatient costs or total medical costs and levels of PA years. This study provides the first empirical evidence about the effects of the intensity and years of PA on hospital service use and expenditure of CHD in China. It suggests that the patients' PA, especially the vigorous PA, should be promoted widely to the public and patients in order to relieve the financial burden of CHD.

12.
Ann Hepatol ; 18(2): 298-303, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31040092

RESUMO

INTRODUCTION AND AIM: It is indicated that high levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are associated with increased incident type 2 diabetes risk. However, whether serum ALT levels could improve the discrimination of type 2 diabetes remains unclear. METHODS: The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. A total of 17,173 participants free of type 2 diabetes at baseline were included and 1159 participants developed diabetes after 4.51 (0.61) years of follow-up. Cox proportional hazard regression model was used to calculate the hazard ratios (HRs) for the association between ALT and AST levels with incident diabetes risk. Receiver-operating characteristic (ROC) curves analysis was used to evaluate the predictive accuracy of models incorporating traditional risk factors with and without ALT. RESULTS: Compared with the lowest quartile of ALT and AST levels, the highest quartile had a significantly higher risk of developing type 2 diabetes (HR: 2.17 [95% CI: 1.78-2.65] and 1.29 [1.08-1.54], respectively) after adjustment for potential confounders. The addition of ALT levels into the traditional risk factors did not improve the predictive ability of type 2 diabetes, with AUC increase from 0.772 to 0.774; P=0.86. CONCLUSIONS: Although elevated ALT or AST levels increased incident type 2diabetes risk, addition of ALT levels into the prediction model did not improve the discrimination of type 2 diabetes.

13.
Acta Diabetol ; 56(9): 1037-1044, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30989380

RESUMO

AIMS: Observational studies indicated that resting heart rate (RHR) was associated with diabetes mellitus (DM) risk; however, it remains unclear whether the association between RHR and DM is causal. We aimed to examine whether there was causal association of RHR with DM risk. METHODS: A prospective study including 16,201 middle-aged and older Chinese (7031 males and 9170 females) derived from the Dongfeng-Tongji cohort was performed. Cox proportional hazard regression models were conducted to estimate the associations between RHR and incident DM risk. In 7481 participants, 65 single nucleotide polymorphisms related to RHR were genotyped. A genetic risk score (GRS) of RHR was calculated based on the RHR-associated variants. The causal associations of RHR with DM risk were investigated by Mendelian randomization analysis. RESULTS: During a mean (SD) follow-up of 4.5 (0.5) years, 1110 diabetes were identified. Compared with the referential RHR group (≤ 60 beats per minute [bpm]), individuals with RHR > 80 bpm have a higher incident diabetes risk, with a hazard ratio of 1.40 (95% confidence interval [CI], 1.05-1.88). With per SD increase in the weighted genetic risk score, the resting heart rate increased by 0.71 bpm (95% CI 0.49-0.93). By using the GRS to estimate the unconfounded effect, we found that higher resting heart rate did not have a causal effect on diabetes risk (OR 1.00 [95% CI 0.95-1.05]). CONCLUSIONS: The present study supported a positive but not a causal association of RHR with incident diabetes risk. More studies are needed to verify our findings.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Diabetes Mellitus/fisiopatologia , Frequência Cardíaca/genética , Polimorfismo de Nucleotídeo Único , Descanso/fisiologia , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Estudos de Coortes , Feminino , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Incidência , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
14.
Diab Vasc Dis Res ; 16(5): 424-430, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31023083

RESUMO

OBJECTIVES: The aim of this study was to investigate the association between serum carbohydrate antigen 125 concentrations and incident type 2 diabetes mellitus risk in a prospective cohort. METHODS: We included 18,983 eligible participants aged 63.1 years derived from the Dongfeng-Tongji cohort at baseline from September 2008 to June 2010, and they were followed until October 2013. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence interval of type 2 diabetes mellitus incidence in relation to carbohydrate antigen 125 concentrations. RESULTS: In all, 1594 incident cases of type 2 diabetes mellitus were observed after a median follow-up of 4.6 years. Carbohydrate antigen 125 concentrations were categorized into four groups according to the quartiles of distribution: <1.1, 1.1-5.6, 5.6-10.0 and ⩾10 U/mL. Compared with participants in the lowest quartile, the hazard ratio (95% confidence interval) of type 2 diabetes mellitus was 0.97 (0.81-1.15), 1.23 (1.05-1.45) and 1.48 (1.27-1.74) for quartile 2-quartile 4 of carbohydrate antigen 125 concentrations after adjustment for potential confounders (p for trend < 0.001). With per-standard deviation increase in carbohydrate antigen 125 levels, the hazard ratio of type 2 diabetes mellitus increased 12% (95% confidence interval, 8-16). CONCLUSION: Findings from this study indicated that serum carbohydrate antigen 125 concentrations were positively correlated with incident type 2 diabetes mellitus risk among a middle-aged and elderly Chinese population.

15.
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.

16.
Environ Int ; 127: 685-693, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30991224

RESUMO

OBJECTIVE: Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms. METHODS: A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues. RESULTS: Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [ß (95% CI) = -0.73 (-1.27, -0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1, APE, TP53BP1, WDR33, LAPTM4B, TRIT1, HUWE1, and ZNF813, which were over-expressed in lung tumor tissues. CONCLUSIONS: We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention.

17.
Hepatology ; 70(1): 451-452, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30820953
18.
J Chin Med Assoc ; 82(5): 351-355, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30893250

RESUMO

BACKGROUND: Cardiovascular disease is a major cause of mortality in patients with end-stage renal disease (ESRD). In addition to arteriosclerosis (arterial stiffness) and atherosclerosis, left ventricular (LV) hypertrophy and LV systolic dysfunction are the major cardiac determinants of cardiovascular mortality in hemodialysis patients. Although LV diastolic dysfunction is common in patients with ESRD, its prognostic value is yet to be established. METHODS: A total of 103 ESRD patients (52 females, 51 males, age 51 ± 14 years) receiving regular hemodialysis and with preserved LV systolic function were prospectively enrolled in the current study. A comprehensive cardiovascular evaluation was performed at baseline. LV diastolic function was assessed using Doppler mitral inflow velocity and tissue Doppler imaging (TDI) of the mitral annulus velocity. Predictors for hospitalization and all-cause mortality were identified via Cox proportional hazards analysis. RESULTS: There were 20 deaths and 46 hospitalizations during a follow-up period of 67.9 ± 20.2 months. After adjusting for age, aortic pulse wave velocity (PWV), and carotid intima media thickness, Cox analysis demonstrated that ratio of early ventricular filling velocity (E) to early diastolic tissue velocity mitral annulus (E') (E/E') was a significant predictor for hospitalization (hazard ratio [HR] 1.235 and 95% CI 1.115-1.368 per-1SD). E' also independently predicted mortality (HR 0.682, 95% CI 0.472-0.985). The TDI parameters significantly correlated with the LV mass index and PWV. CONCLUSION: The findings of the current study suggest that diastolic function, as indexed by TDI, is an independent predictor of hospitalization and mortality in ESRD patients receiving regular hemodialysis and with preserved LV systolic function. The TDI parameters may reflect the impairment of arterial function and LV pressure overload.

19.
Sci Rep ; 9(1): 980, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30700753

RESUMO

Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0-5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00-1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39-4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03-1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37-1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.

20.
Fish Shellfish Immunol ; 87: 184-192, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30641185

RESUMO

The liver-expressed antimicrobial peptide 2 (LEAP-2) plays a vital role in host immunity against pathogenic organisms. In the present study, cDNA of the LEAP-2 gene was cloned and sequenced from the barbel steed (Hemibarbus labeo). The predicted amino acid sequence of the barbel steed LEAP-2 comprises a signal peptide and a prodomain, which is followed by the mature peptide. Sequence analysis revealed that barbel steed LEAP-2 belongs to the fish LEAP-2A cluster and that it is closely related to zebrafish LEAP-2A. We found that barbel steed LEAP-2 transcripts were expressed in a wide range of tissues, with the highest mRNA levels detected in the liver. In response to lipopolysaccharide (LPS) treatment, LEAP-2 was significantly upregulated in the liver, head kidney, spleen, gill, and mid intestine. A chemically synthesized LEAP-2 mature peptide exhibited selective antimicrobial activity against several bacteria in vitro. Moreover, LEAP-2, alone or in combination with LPS or phorbol 12-myristate 13-acetate, strongly induced a pro-inflammatory reaction in barbel steed monocytes/macrophages (MO/MФ), involving the induction of iNOS activity, respiratory burst, and the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-1ß. Collectively, the results of this study indicate the importance of fish LEAP-2 in the M1-type polarization of MO/MΦ.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Hepcidinas/genética , Hepcidinas/imunologia , Imunidade Inata/genética , Sequência de Aminoácidos , Animais , Bactérias/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Hepcidinas/química , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Monócitos/metabolismo , Filogenia , Alinhamento de Sequência/veterinária
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