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1.
Biosens Bioelectron ; 196: 113703, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656853

RESUMO

A sandwiched photoelectrochemical (PEC) immunosensor based on BiOI/Bi2S3/Ag2S was designed for the quantitative detection of cytokeratin-19 fragments (CYFRA21-1) in serum. In this work, due to the intervention of the narrow band gap Bi2S3, the absorption of the light source by the BiOI/Bi2S3 heterostructure has been significantly enhanced. Meanwhile, the matched band structure of BiOI, Bi2S3 and Ag2S promoted the rapid transfer of electrons between the conduction bands and effectively inhibited the recombination of electron-hole pairs, thus enhanced the photoelectric signals. Sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) with up-conversion luminescence properties provided more light energy for the base materials. On the other hand, S,N-CQDs were combined with Ab2 through polydopamine (PDA), as secondary antibody labels, further enhanced the sensitivity of the sensor. Herein, the linear range of the sensor was from 0.001 to 100 ng mL-1 and the detection limit was 1.72 pg mL-1. In addition, the sensor provides a feasible way for the detection of tumor markers due to its excellent selectivity, repeatability and good stability.

2.
IEEE Trans Image Process ; 30: 6943-6956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34343091

RESUMO

In zero-shot learning (ZSL) community, it is generally recognized that transductive learning performs better than inductive one as the unseen-class samples are also used in its training stage. How to generate pseudo labels for unseen-class samples and how to use such usually noisy pseudo labels are two critical issues in transductive learning. In this work, we introduce an iterative co-training framework which contains two different base ZSL models and an exchanging module. At each iteration, the two different ZSL models are co-trained to separately predict pseudo labels for the unseen-class samples, and the exchanging module exchanges the predicted pseudo labels, then the exchanged pseudo-labeled samples are added into the training sets for the next iteration. By such, our framework can gradually boost the ZSL performance by fully exploiting the potential complementarity of the two models' classification capabilities. In addition, our co-training framework is also applied to the generalized ZSL (GZSL), in which a semantic-guided OOD detector is proposed to pick out the most likely unseen-class samples before class-level classification to alleviate the bias problem in GZSL. Extensive experiments on three benchmarks show that our proposed methods could significantly outperform about 31 state-of-the-art ones.

3.
Medicine (Baltimore) ; 100(31): e26693, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397804

RESUMO

ABSTRACT: Previous studies had shown that an increased aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) was associated with cardiovascular disease. This study aimed to assess the relationship between AST/ALT ratio and all-cause and cardiovascular mortality in patients with hypertension.By March 31, 2020, a cohort of 14,220 Chinese hypertensive patients was followed up. The end point was all-cause and cardiovascular death. Hazard ratios (HRs) and 95% CIs were calculated for mortality associated with AST/ALT ratio, using Cox proportional hazards models and competing risk model.In an average of 1.7 years of follow-up, 1.39% (n = 198) of patients died, 55.5% (n = 110) of whom from cardiovascular disease. AST/ALT ratio was associated with increased risk of all-cause death (HR:1.37, 95% CI:1.15-1.63) and cardiovascular death (HR:1.32, 95% CI:1.03-1.68) after adjustment for other potential confounders. Compared with low AST/ALT ratio (Tertile 1), high AST/ALT ratio was associated with high cause mortality (Tertile 2: HR:1.35, 95% CI:0.86-2.10; Tertile 3: HR:2.10, 95% CI:1.37-3.21; P for trend <.001). Compared with low AST/ALT ratio (Tertile 1), a statistically significant increased risk of cardiovascular mortality was also observed (Tertile 2: HR:1.27, 95% CI:0.70-2.29; Tertile 3: HR:1.92, 95% CI:1.09-3.37; P for trend <.001). High AST/ALT ratio was also associated with high cardiovascular mortality (Tertile 2: HR:1.27, 95% CI:0.70-2.29; Tertile 3: HR:1.92, 95% CI:1.09-3.37; P for trend <.001).Present study indicated that increased AST/ALT ratio levels were predictive of all-cause and cardiovascular mortality among Chinese hypertensive patients.Trial registration: CHICTR, CHiCTR1800017274. Registered 20 July 2018.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hipertensão/sangue , Hipertensão/mortalidade , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco
4.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360958

RESUMO

Semi-dwarfism is a main agronomic trait in crop breeding. In this study, we performed genome-wide association study (GWAS) and identified a new quantitative trait nucleotide (QTN) for rice shoot length. The peak QTN (C/T) was located in the first coding region of a group III WRKY transcription factor OsWRKY21 (LOC_Os01g60640). Interestingly, further haplotype analysis showed that C/T difference only existed in the indica group but not in the japonica group, resulting in significant differences in plant height among the different indica rice varieties. OsWRKY21 was expressed in embryo, radicle, shoots, leaves, and stems. Most notably, overexpressing OsWRKY21 resulted in the semi-dwarf phenotype, early heading date and short internodes compared to the wild type, while the knockout mutant plants by CRISPR/Cas9 technology yielded the opposite. The overexpressing lines exhibited the decreased length of the cells near sclerenchyma epidermis, accompanied with the lower levels of indole-3-acetic acid (IAA) and gibberellin 3 (GA3), but increased levels of the abscisic acid (ABA) and salicylic acid (SA) in the internodes at heading stage. Moreover, the semi-dwarf phenotype could be fully rescued by exogenous GA3 application at seedling stage. The RNA-seq and qRT-PCR analysis confirmed the differential expression levels of genes in development and the stress responses in rice, including GA metabolism (GA20ox2, GA2ox6, and YABY1) and cell wall biosynthesis (CesA4, 7, and 9) and regulation (MYB103L). These data suggest the essential role of OsWRKY21 in regulation of internode elongation and plant height in rice.


Assuntos
Oryza/genética , Proteínas de Plantas/genética , Caules de Planta/crescimento & desenvolvimento , Locos de Características Quantitativas , Fatores de Transcrição/genética , Estudo de Associação Genômica Ampla , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Melhoramento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Caules de Planta/genética , Característica Quantitativa Herdável
5.
J Hum Hypertens ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158592

RESUMO

Data regarding the association of the waist-to-height ratio (WHtR) with hypertension (HTN) are conflicting. Moreover, little information is available on the association between WHtR and HTN subtypes. Therefore, we aimed to investigate the associations between WHtR and the prevalence of HTN and its subtypes in a Chinese population. In the cross-sectional analysis, 13,947 adults from the China Hypertension Survey study were analysed. We examined the relationship between WHtR and the prevalence of HTN and its subtypes (isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systodiastolic hypertension (SDH)) using multivariate logistic regression analysis. A generalized additive model (GAM) and smooth curve fitting (penalized spline method) were also used. Overall, the mean WHtR was 0.50. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for HTN, ISH, IDH and SDH for each standard deviation (SD) increase in WHtR were 1.53 (1.45-1.61), 1.36 (1.28-1.44), 1.41 (1.20-1.65) and 1.47 (1.36-1.59), respectively. The fully adjusted smooth curve fitting revealed a linear association between WHtR and HTN, ISH, IDH, and SDH. Moreover, the positive associations between WHtR and HTN and its subtypes were more strong among younger adults (<60 compared with ≥60 years, P values for interaction <0.001). These findings suggested that WHtR was positively associated with HTN and its subtypes, especially among younger adults (<60 years) in southern China.

6.
Biol Sex Differ ; 12(1): 39, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051856

RESUMO

BACKGROUND: To date, there is no clearly defined association between plasma selenium levels and first stroke. We aimed to investigate the association between baseline plasma selenium and first stroke risk in a community-based Chinese population. METHODS: Using a nested case-control study design, a total of 1255 first stroke cases and 1255 matched controls were analyzed. Participant plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS), and the association of plasma selenium with first stroke risk was estimated by conditional logistic regression models. RESULTS: Overall, a non-linear negative association between plasma selenium and first total stroke and first ischemic stroke risks was found in males but not in females. Compared with participants with lower selenium levels (tertile 1-2, < 94.1 ng/mL), participants with higher selenium levels (tertile 3, ≥ 94.1 ng/mL) had significantly lower risks of first total stroke (OR 0.63; 95% CI 0.48, 0.83) and first ischemic stroke (OR 0.61; 95% CI 0.45, 0.83) in males but not in females with first total stroke (OR 0.92; 95% CI 0.69, 1.22) and first ischemic stroke (OR 0.89; 95% CI 0.65, 1.22). Furthermore, a stronger association between plasma selenium and first total stroke was found in males with higher vitamin E levels (≥ 13.5 µg/mL vs. < 13.5 µg/mL P-interaction = 0.007). No significant association was observed between plasma selenium and first hemorrhagic stroke risk in either males or females. CONCLUSION: Our study indicated a significant, non-linear, negative association between plasma selenium and first stroke in males but not in females. TRIAL REGISTRATION: ChiCTR1800017274 .

8.
Angiology ; 72(10): 916-922, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33779311

RESUMO

Previous studies reported that the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT) was a risk factor in cardiovascular disease. Peripheral artery disease (PAD) is an important risk factor for cardiovascular death. However, only a few studies investigated the correlations between the AST/ALT ratio and PAD. We analyzed data from 10 900 patients with hypertension from the Chinese Hypertension Registry Study; 350 patients had PAD (prevalence 3.2%). After adjusting for potential confounders, the AST/ALT ratio was independently and positively associated with risk of PAD (OR: 1.31, 95% CI, 1.13-1.59), and a significant increased risk of PAD for the third AST/ALT ratio tertile (T3) compared with the first tertile (T1; OR: 1.49, 95% CI, 1.09-2.04, Ptrend = .005) was found. Moreover, when we combined T1 and T2 into one group and used it as a reference group, the risk of PAD increased with the increase in AST/ALT; the risk ratio was 1.52 (95% CI, 1.20-1.95). A higher AST/ALT ratio (≥1.65) was associated with PAD risk in Chinese adults with hypertension. Our results suggest that the AST/ALT ratio may help identify patients at high risk of vascular end points and might be a convenient, economical, and effective tool for evaluating the risk of atherosclerosis.

9.
J Nutr ; 151(6): 1394-1400, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33693869

RESUMO

BACKGROUND: Risk of chronic kidney disease (CKD) is higher in normal-weight metabolically unhealthy people, especially when combined with hypertension. In this context, whether the visceral adiposity index (VAI), which reflects body fat distribution and metabolism, can be used to identify the risk of CKD among normal-weight hypertensive patients is unclear. OBJECTIVES: This study aimed to evaluate the association between VAI and renal function in normal-weight hypertensive patients. METHODS: In this cross-sectional study, 8591 hypertensive patients with normal BMI from the China H-type Hypertension Registry Study were analyzed. The VAI was calculated with serum triglycerides, serum HDL cholesterol, waist circumference, and BMI. VAI was ln-transformed for analysis on account of the skewed distribution. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL · min-1 · 1.73 m-2. Multivariable linear and multivariable logistic regression analyses were performed to evaluate the association of VAI with eGFR and CKD. RESULTS: The prevalence rate of CKD was 10.1%. Multivariable linear regression analyses showed that an elevated lnVAI reduced eGFR by 2.63 mL · min-1 · 1.73 m-2 (95% CI: -3.54, -1.72 mL · min-1 · 1.73 m-2). Multivariable logistic regression analysis showed that an elevated lnVAI was independently associated with the prevalence of CKD (OR: 1.59; 95% CI: 1.31, 1.93). As possible confounding factors were removed the association became greater. The higher the VAI was, the greater the decrease in eGFR and the higher the risk of CKD. No significant interactions were found in any of the subgroups (age, sex, physical activity, current smoking, current drinking, fasting glucose, LDL cholesterol, blood pressure, and antihypertensive drugs). CONCLUSIONS: VAI, as a simple surrogate measure of visceral fat accumulation, is independently and inversely associated with renal function in normal-weight Chinese hypertensive adults.This trial was registered at chictr.org.cn as ChiCTR1800017274.

10.
Clin Nutr ; 40(6): 4316-4323, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33581953

RESUMO

BACKGROUND & AIMS: Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. METHODS: In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality. RESULTS: A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 [standard deviation (SD) 1.22] servings per day. During a median follow-up of 8.9 years [interquartile range (IQR) 6.7-9.9 years], we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio [HR] trend 0.92, 95% CI 0.86-0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97-1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84-1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89-1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82-1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55-0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86-0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90-0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89-0.99, p trend = 0.020) in the fully adjusted models. CONCLUSIONS: This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500-625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.

11.
Nutr Neurosci ; : 1-10, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535911

RESUMO

BACKGROUND AND AIMS: Uncertainty remains regarding the association between the risk of stroke and plasma copper levels in population with copper mostly in normal range due to limited data. We examined the association between baseline plasma copper and risk of first stroke in Chinese community-dwelling population. METHODS: We conducted a nested case control study from 'H-type Hypertension and Stroke Prevention and Control Project'. A total of 1255 first stroke cases and 1255 controls matched for age, sex and study site were included in the analysis. Conditional logistic regression analyses were performed to evaluate the association between plasma copper and first stroke. RESULTS: The overall mean of copper was 15.90 (2.66) µmol/L. In total, 94.26% participants' copper concentration was in the normal range by Mayo Clinic laboratory reference values. Smoothing curve showed that the associations of plasma copper with first stroke and its subtypes were linear. Each standard deviation (SD) increment of plasma copper was independently and positively associated with risk of first stroke [odds ratio (OR): 1.17, 95% confidence interval (CI): 1.07-1.28]. The multivariable ORs with 95% CIs for total stroke, ischemic stroke and hemorrhagic stroke in the highest versus the lowest quartile of plasma copper were 1.49 (1.16-1.90; P-trend = 0.001), 1.46 (1.12-1.92; P-trend = 0.004) and 2.05 (0.95-4.38; P-trend = 0.050), respectively. CONCLUSIONS: Baseline plasma copper was positively associated with risk of first ischemic stroke in an approximately linear fashion among Chinese community population (80.32% hypertensives), although their copper levels were mostly within the normal range according to current reference values. Our findings warrant additional investigation.

12.
Analyst ; 146(6): 1996-2008, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33507168

RESUMO

A series of natural, environmentally friendly and low-cost menthol-based hydrophobic deep eutectic solvents (DES) were synthesized to extract and concentrate solutes from dilute aqueous solutions, especially triphenylmethane (TPM) dye micropollutants. The system has excellent extraction performance for TPM. Density functional theory (DFT) and molecular dynamics (MD) simulation were used to quantitatively analyze the effect of the DES composition and TPM structure on the distribution of target molecules in two phases. The solvation free energy of ethyl violet (EV) in DES (-17.128 to -21.681 kcal mol-1) is much larger than that in water (-0.411 kcal mol-1), and increases with the increase of the HBD chain length, which is proportional to the extraction rate, indicating that the TPM molecules are more inclined to the DES environment, especially long-chain DES, than aqueous solution. For the same C12DES, the extraction efficiency of the TPM dyes follows the order: ethyl violet (EV) (99.9%) > crystal violet (CV) (99.6%) > methyl violet (MV) (98.8%). EV has the smallest positive charge and the smallest dipole moment (9.109 D), and the Flory-Huggins parameters of EV (χEV-C12DES 0.053) relative to MV and CV are the smallest in C12DES, and are also the largest in water (χEV-H2O 0.053), indicating that EV has the largest polarity difference with H2O and is more easily detached from water and compatible with the long-chain DES phase. The motion of EV and MV on the phase interface of DES and water was calculated to further analyze from the molecular level. At the same time, EV tends to move into the DES phase. In summary, the excellent extraction ability of DES for TPM is verified through experiments and simulations, providing solid theoretical support in terms of separation in other fields.

13.
J Biochem ; 169(1): 43-53, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32706888

RESUMO

It is urgent to understand the regulatory mechanism of drug resistance in widespread bacterial pathogens. In Mycobacterium tuberculosis, several transcriptional regulators have been found to play essential roles in regulating its drug resistance. In this study, we found that an ArsR family transcription regulator encoded by Rv2642 (CdiR) responds to isoniazid (INH), a widely used anti-tuberculosis (TB) drug. CdiR negatively regulates self and adjacent genes, including arsC (arsenic-transport integral membrane protein ArsC). CdiR directly interacts with INH and Cd(II). The binding of INH and Cd(II) both reduce its DNA-binding activity. Disrupting cdiR increased the drug susceptibility to INH, whereas overexpressing cdiR decreased the susceptibility. Strikingly, overexpressing arsC increased the drug susceptibility as well as cdiR. Additionally, both changes in cdiR and arsC expression caused sensitivity to other drugs such as rifamycin and ethambutol, where the minimal inhibitory concentrations in the cdiR deletion strain were equal to those of the arsC-overexpressing strain, suggesting that the function of CdiR in regulating drug resistance primarily depends on arsC. Furthermore, we found that Cd(II) enhances bacterial resistance to INH in a CdiR-dependent manner. As a conclusion, CdiR has a critical role in directing the interplay between Cd(II) metal ions and drug susceptibility in mycobacteria.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias/metabolismo , Cádmio/metabolismo , Isoniazida/farmacologia , Mycobacterium tuberculosis/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Etambutol/farmacologia , Regulação Bacteriana da Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana/métodos , Mycobacterium/genética , Mycobacterium/metabolismo , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Rifamicinas/farmacologia , Fatores de Transcrição/genética
14.
J Clin Hypertens (Greenwich) ; 23(1): 114-121, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33200878

RESUMO

We aimed to evaluate the relation of the ankle-brachial index (ABI) with the prevalence of stroke and to examine any possible effect modifiers among hypertensive patients without atrial fibrillation. A total of 10 750 subjects with hypertension aged 27-96 years were included in the current study. The outcome was a stroke. Odds ratios of stroke concerning ABI were calculated using multivariate logistic regression models. Among 10 750 hypertensive participants, 690 (6.42%) had a stroke. Multivariate logistic analyses showed that ABI was negatively correlated with the prevalence of stroke (per SD increment; adjusted OR, 0.88; 95% CI, 0.82-0.94). Compared with participants in Q 1, the odds ratios (95% CI) for those in the Q2 (1.05 to 1.10), Q3 (1.10 to 1.15), and Q4 (≥1.15) were 0.71 (0.56, 0.90), 0.87 (0.70, 1.08), and 0.81 (0.65, 1.01), respectively. However, compared with higher ABI value, lower ABI value (<1.05) would significantly increase the odds of stroke (OR: 1.26, 95% CI [1.05-1.50]), especially in the elderly over 65 years old. A generalized additive model and a smooth curve fitting showed that there existed an L-shaped association between ABI and the prevalence of stroke. Our results suggest that an L-shaped association between ABI and the prevalence of stroke was found in general hypertensive patients, with a turning point at about 1.05. Compared with higher ABI value, lower ABI value (<1.05) would significantly increase the prevalence of stroke (OR: 1.26, 95% CI [1.05-1.50]), especially in the elderly over 65 years old.


Assuntos
Fibrilação Atrial , Hipertensão , Acidente Vascular Cerebral , Idoso , Índice Tornozelo-Braço , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
15.
J Cell Mol Med ; 25(4): 2190-2202, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33369138

RESUMO

Diabetic retinopathy (DR) is the most prevalently occurring microvascular complication in diabetic patients that triggers severe visual impairments. The anti-angiogenesis role of FBXW7 has been identified in breast cancer. Therefore, this study intends to decipher the mechanism of FBXW7 in angiogenesis of DR. DR model was induced on mice using high-glucose (HG) and high-fat diet, and retinal microvascular endothelial cells (RMECs) isolated from normal mice were induced with HG, followed by evaluation of FBXW7, Ki67, HIF-1α and VEGF expression by immunofluorescence, immunohistochemistry or Western blot analysis. After gain- and loss-of-function assays in normal and DR mice, angiogenesis was assessed by CD31 fluorescence staining and Western blot analysis. After ectopic expression and silencing experiments in HG-induced RMECs, RMEC proliferation, migration and angiogenesis were, respectively, determined by EdU, Transwell and in vitro angiogenesis assays. The impact of FBXW7 on the ubiquitination of c-Myc was studied by cycloheximide chase assay and proteasome inhibition, and the binding of c-Myc to HDAC2 promoter by dual-luciferase reporter gene experiment. DR mice and HG-induced RMECs possessed down-regulated FBXW7 and up-regulated Ki67, HIF-1α and VEGF. Silencing FBXW7 enhanced angiogenesis in normal mouse retinal tissue, but overexpressing FBXW7 or silencing c-Myc diminished angiogenesis in DR mouse retinal tissue. Overexpressing FBXW7 or silencing c-Myc depressed proliferation, migration and angiogenesis in HG-induced RMECs. FBXW7 induced c-Myc ubiquitination degradation, and c-Myc augmented HDAC2 expression by binding to HDAC2 promoter. Conclusively, our data provided a novel sight of anti-angiogenesis role of FBXW7 in DR by modulating the c-Myc/HDAC2 axis.


Assuntos
Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Proteína 7 com Repetições F-Box-WD/genética , Histona Desacetilase 2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Animais , Biomarcadores , Movimento Celular , Proliferação de Células , Retinopatia Diabética/patologia , Proteína 7 com Repetições F-Box-WD/metabolismo , Imunofluorescência , Expressão Gênica , Regulação da Expressão Gênica , Inativação Gênica , Histona Desacetilase 2/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia , Imuno-Histoquímica , Masculino , Camundongos , Regiões Promotoras Genéticas , Proteólise , Ubiquitinação , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Sci Total Environ ; 752: 141824, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896789

RESUMO

Chromium (Cr) can coexist with other heavy metals in the blood of chronically chromate-exposed individuals. However, few studies have explored the health impacts of other hazardous metals after exposure to hexavalent chromium [Cr(VI)]. This study aimed to assess the modification effects of blood lead (Pb) on the genetic damage induced by Cr(VI). During 2010-2019, 1000 blood samples were collected from 455 workers exposed to chromate and 545 workers not exposed to chromate from the same factory with similar labor intensity. The levels of Cr and Pb were measured in whole blood samples. Micronucleus frequency (MNF) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured to reflect different types of genetic damage. Multivariate linear regression analyses were performed to evaluate the associations between hazardous metals and the modification effects of Pb on genetic damage. The geometric mean levels of Cr and Pb in the exposure group were significantly higher than those in the control group [Cr: 6.42 (6.08- 6.79) vs. 1.29 (1.22- 1.36) µg/L; Pb: 38.82 (37.22- 40.50) vs. 34.47 (33.15- 35.85) µg/L]. The geometric means of urinary 8-OHdG and MNF in exposure group were 4.00 (3.64- 4.40) µg/g and 5.40 (4.89- 5.97) ‰, respectively, significantly higher than the 3.20 (2.94- 3.48) µg/g and 4.57 (4.15- 5.03) ‰, respectively, in control group. log2Cr was independently and positively associated with urinary 8-OHdG (ß-adjusted = 0.143, 95% CI: 0.082- 0.204) and MNF (ß-adjusted = 0.303, 95%CI: 0.020- 0.587). With the change in circulating Pb levels, the types of genetic damage induced by Cr(VI) were different. At low levels of circulating Pb (<30.80 µg/L), chromate mainly caused changes in 8-OHdG, while at high circulating Pb levels (≥44.88 µg/L), chromate induced alterations in MNF. The findings suggested that chromate exposure could cause multiple types of genetic damage, and circulating Pb might modify the association between circulating Cr and the form of genetic damage.


Assuntos
Cromatos , Exposição Ocupacional , Cromatos/toxicidade , Cromo/toxicidade , Estudos Epidemiológicos , Humanos , Chumbo/toxicidade , Exposição Ocupacional/análise
17.
Anal Biochem ; 612: 114012, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189703

RESUMO

A sandwich-type electrochemiluminescence (ECL) immunosensor based on the resonance energy transfer (RET) was proposed for ultrasensitive detection of cardiac troponin I (cTnI). The RET behavior could be generated between graphite carbon nitride nanosheets (m-CNNS) as donor and copper oxide@graphene oxide (CuO@GO) as acceptor, achieving the quenching effect of CuO@GO on m-CNNS for cTnI detection. The m-CNNS synthesized by mechanical grinding of the graphite carbon nitride (CN) not only has better dispersion and higher specific surface area, but also has high luminous efficiency and stable chemical properties. Therefore, m-CNNS was used as the matrix material and luminophore. As the acceptor, CuO@GO prepared by in-situ chemical synthesis of CuO NPs onto GO sheets also has a high specific surface area, which could be used as a label of secondary antibody (Ab2). Under optimal conditions, cTnI could be determined within the linear range of 0.1 pg mL-1 to 100 ng mL-1 and had a low detection limit (0.028 pg mL-1, S/N = 3). Meanwhile, the prepared ECL immunosensor possessed great stability, specificity and reproducibility, providing a new method for detecting cTnI and other biomarkers.


Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Fluorimunoensaio/métodos , Troponina I/análise , Troponina I/sangue , Anticorpos Imobilizados/química , Cobre/química , Grafite/síntese química , Grafite/química , Humanos , Limite de Detecção , Nanoestruturas/química , Compostos de Nitrogênio/química , Reprodutibilidade dos Testes
18.
Lipids Health Dis ; 19(1): 231, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143696

RESUMO

BACKGROUND: Data on the relationship between nontraditional lipid profiles [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C)] and the risk of peripheral artery disease (PAD) are limited. The present study investigated the relationship of nontraditional lipid indices with PAD in hypertensive patients. METHODS: This cross-sectional study was performed among 10,900 adults with hypertension. Participants were diagnosed with PAD when their ankle-brachial index (ABI) was < 0.9. The association between nontraditional lipid profiles and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline. RESULTS: All nontraditional lipid indices were independently and positively associated with PAD in a dose-response fashion. After multivariable adjustment, the per SD increments of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C were all significantly associated with 37, 14, 40, and 24% higher risk for PAD, respectively. The adjusted ORs (95% CI) for PAD were 1.77 (1.31, 2.40), 1.71 (1.25, 2.34), 2.03 (1.50, 2.74), and 1.70 (1.25, 2.31) when comparing the highest tertile to the lowest tertile of the TC/HDL-C, TG/HDL-C, LDL-C/HDL-C ratios and non-HDL-C, respectively. CONCLUSIONS: Among Chinese hypertensive adults, all nontraditional lipid indices were positively associated with PAD, and the LDL-C/HDL-C and TC/HDL-C ratios were better than the other nontraditional lipid indices for predicting PAD. These findings may improve the risk stratification of cardiovascular disease and dyslipidemia management. TRIAL REGISTRATION: CHiCTR, ChiCTR1800017274 . Registered 20 July 2018.

19.
J Ren Nutr ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33131976

RESUMO

OBJECTIVE: Data on the association between homocysteine (Hcy) and the risk of chronic kidney disease (CKD) in patients with H-type hypertension were limited. This study aimed to examine the relation of Hcy with the prevalence of CKD and estimated glomerular filtration rate (eGFR) among Chinese adults with H-type hypertension. METHODS: A total of 12,873 Chinese adults with H-type hypertension aged 27-75 years were enrolled in the final analysis. Hcy concentrations were divided into 11 groups at 2 µmol/L interval. The outcome was CKD, defined as eGFR <60 mL/min/1.73 m2. RESULTS: The prevalence of CKD was 7.58%, and the mean Hcy was 17.58 ± 10.96 µmol/L. The smoothing curve indicated that with the increase of Hcy, the prevalence of CKD increases first and then flattens, eGFR decreases first and then flattens, which supports the L-shaped association of Hcy with the prevalence of CKD and eGFR. Moreover, we further found the inflection point of Hcy was 22 µmol/L. OR (95% CI) of risk of CKD was 1.31 (1.28, 1.35) on the left side of an inflection point and 1.00 (0.99, 1.01) on the right of an inflection point, ß (95% CI) of eGFR was -1.58 (-1.65, -1.50) on the left side of an inflection point and 0.00 (-0.03, 0.03) on the right of an inflection point, respectively. Similar results were found in various subgroups. CONCLUSIONS: Our study suggested saturation effects of Hcy on the prevalence of CKD and eGFR among Chinese patients with H-type hypertension.

20.
Int J Endocrinol ; 2020: 9725979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014048

RESUMO

Background: Evidence regarding the nonlinear relationship between serum uric acid (SUA) and blood lipids in Chinese population with hypertension is limited. Therefore, the present study aimed to investigate whether there is a nonlinear association between SUA and lipids in Chinese hypertensive population with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2. Methods: A total of 13,355 hypertensive participants with eGFR ≥30 ml/min/1.73 m2 were selected from the Chinese Hypertension Registry Study. Multivariate linear regression was used to examine the linear relationship between SUA and lipids. Smooth curve fitting (penalized spline method) and threshold saturation effects were used to analyze the nonlinear association between SUA and lipids. Results: In the fully adjusted model, the results showed a positive correlation between SUA and TG (ß = 0.15; 95% CI: 0.14, 0.16) and LDL-C (ß = 0.06; 95% CI: 0.05, 0.07), respectively. However, the relationship between SUA and HDL-C was nonlinear. The inflection point of SUA was 7.24 mg/dL. On the left side of the inflection point (<7.24 mg/dL), SUA was negatively associated with HDL-C (ß = -0.02; 95% CI -0.02, -0.01). On the right side of the inflection point (≥7.24 mg/dL), SUA was not related to HDL-C (ß = 0.01; 95% CI -0.01, 0.02). Conclusion: After adjusting for all covariates, SUA was positively associated with TG and LDL-C. The relationship between SUA and HDL-C was nonlinear. The negative correlation between SUA and HDL-C only existed when the SUA was less than 7.24 mg/dL in a hypertensive population with eGFR ≥30 ml/min/1.73 m2.

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