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1.
Mamm Genome ; 35(2): 241-255, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38512459

RESUMO

Schizophrenia is a debilitating psychiatric disorder that can significantly affect a patient's quality of life and lead to permanent brain damage. Although medical research has identified certain genetic risk factors, the specific pathogenesis of the disorder remains unclear. Despite the prevalence of research employing magnetic resonance imaging, few studies have focused on the gene level and gene expression profile involving a large number of screened genes. However, the high dimensionality of genetic data presents a great challenge to accurately modeling the data. To tackle the current challenges, this study presents a novel feature selection strategy that utilizes heuristic feature fusion and a multi-objective optimization genetic algorithm. The goal is to improve classification performance and identify the key gene subset for schizophrenia diagnostics. Traditional gene screening techniques are inadequate for accurately determining the precise number of key genes associated with schizophrenia. Our innovative approach integrates a filter-based feature selection method to reduce data dimensionality and a multi-objective optimization genetic algorithm for improved classification tasks. By combining the filtering and wrapper methods, our strategy leverages their respective strengths in a deliberate manner, leading to superior classification accuracy and a more efficient selection of relevant genes. This approach has demonstrated significant improvements in classification results across 11 out of 14 relevant datasets. The performance on the remaining three datasets is comparable to the existing methods. Furthermore, visual and enrichment analyses have confirmed the practicality of our proposed method as a promising tool for the early detection of schizophrenia.


Assuntos
Algoritmos , Esquizofrenia , Esquizofrenia/genética , Humanos , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença , Transcriptoma/genética , Biologia Computacional/métodos
2.
Opt Express ; 32(6): 10419-10428, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571254

RESUMO

Twisted stacking of two-dimensional materials with broken inversion symmetry, such as spiral MoTe2 nanopyramids and supertwisted spiral WS2, emerge extremely strong second- and third-harmonic generation. Unlike well-studied nonlinear optical effects in these newly synthesized layered materials, photoluminescence (PL) spectra and exciton information involving their optoelectronic applications remain unknown. Here, we report layer- and power-dependent PL spectra of the supertwisted spiral WS2. The anomalous layer-dependent PL evolutions that PL intensity almost linearly increases with the rise of layer thickness have been determined. Furthermore, from the power-dependent spectra, we find the power exponents of the supertwisted spiral WS2 are smaller than 1, while those of the conventional multilayer WS2 are bigger than 1. These two abnormal phenomena indicate the enlarged interlayer spacing and the decoupling interlayer interaction in the supertwisted spiral WS2. These observations provide insight into PL features in the supertwisted spiral materials and may pave the way for further optoelectronic devices based on the twisted stacking materials.

3.
Anal Chem ; 95(2): 1566-1573, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36584357

RESUMO

Effective monitoring of the physiological progression of acute lung injury (ALI) in real time is crucial for early theranostics to reduce its high mortality. In particular, activatable fluorescence and photoacoustic molecule probes have attracted attention to assess ALI by detecting related indicators. However, the existing fluorophores often encounter issues of low retention in the lungs and slow clearance from the body, which compromise the probe's actual capability for in situ imaging by intravenous injection in vivo. Herein, a novel near-infrared hemicyanines fluorophore (FJH) bearing a quaternary ammonium group was first developed by combining with the rational design and screening strategy. The properties of good hydrophilicity and blood circulation effectively enable FJH accumulation for lung imaging. Inspired by the high retention efficiency, the probe FJH-C that turns on fluorescence and photoacoustic signals in response to the ALI indicator (esterase) was subsequently synthesized. Notably, the probe FJH-C successfully achieved the selectivity and sensitivity toward esterase in vitro and in living cells. More importantly, FJH-C can be further used to assess lipopolysaccharides and silica-induced ALI through the desired fluo-photoacoustic signal. Therefore, this study not only shows the first activatable probe for real-time imaging of lung function but also highlights the fluorophore structure with high lung retention. It is believed that FJH and FJH-C can serve as an efficient platform to reveal the pathological progression of other lung diseases for early diagnosis and medical intervention.


Assuntos
Lesão Pulmonar Aguda , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/química , Diagnóstico por Imagem , Análise Espectral , Sondas Moleculares , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/diagnóstico por imagem , Imagem Óptica
4.
Anal Chem ; 95(17): 6863-6870, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37074120

RESUMO

Effective monitoring of essential bioindicators with high-contrast fluorescence imaging is highly crucial to reveal the pathological progression of diseases. However, most reported probes based on asymmetric amino-rhodamine (ARh) derivatives are often limited in practical application due to the low signal-to-noise ratios. Herein, a new fluorophore, 3-methoxy-amino-rhodamine (3-MeOARh), with improved fluorescence quantum yield (0.51 in EtOH) is designed and synthesized by introducing methoxy group in the ortho-position of amino in asymmetric amino-rhodamine. Notably, the good properties of the ortho-compensation effect further effectively enable the construction of an activatable probe with a high signal-to-noise ratio. As a proof of concept, the probe (3-MeOARh-NTR) was successfully synthesized for nitroreductase detection with high selectivity, excellent sensitivity, and good stability. More importantly, the relationship between drug-induced kidney hypoxia and elevated nitroreductase concentration was first uncovered in living tissues through high-contrast imaging. Therefore, the study presents the activatable probe for kidney hypoxia imaging while highlighting the 3-MeOARh structure with a satisfactory signal-to-noise ratio. It is believed that 3-MeOARh can serve as an efficient platform for activatable probe construction to reveal the pathological progression of different diseases.


Assuntos
Injúria Renal Aguda , Corantes Fluorescentes , Humanos , Rodaminas , Corantes Fluorescentes/química , Imagem Óptica/métodos , Nitrorredutases , Hipóxia
5.
Opt Express ; 31(6): 9350-9361, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157507

RESUMO

The competition mechanism of exciton decay channels in the multilayer TMDs remains poorly understood. Here, the exciton dynamics in the stacked WS2 was studied. The exciton decay processes are divided into the fast and slow decay processes, which are dominated by the exciton-exciton annihilation (EEA) and defect-assisted recombination (DAR), respectively. The lifetime of EEA is on the order of hundreds of femtoseconds (400∼1100 fs). It is decreased initially, followed by an increase with adding layer thickness, which can be attributed to the competition between phonon-assisted effect and defect effect. The lifetime of DAR is on the timescale of hundreds of picoseconds (200∼800 ps), which is determined by the defect density especially in a high injected carrier density.

6.
Biomacromolecules ; 24(9): 4240-4252, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37585281

RESUMO

Bionic mimics using natural cartilage matrix molecules can modulate the corresponding metabolic activity by improving the microenvironment of chondrocytes. A bionic brush polymer, HA/PX, has been found to reverse the loss of cartilage extracellular matrix (ECM) and has promising applications in the clinical treatment of osteoarthritis (OA). However, the unknown bioremediation mechanism of HA/PX severely hinders its clinical translation. In OA, the massive loss of the ECM may be attributed to a decrease in transient receptor potential vanilloid 4 (TRPV4) activity, which affects reactive oxygen species (ROS) clearance and [Ca2+]i signaling, initiating downstream catabolic pathways. In this study, we investigated the bioremediation mechanism of HA/PX in a model of interleukin 1ß (IL-1ß)-induced inflammation. Through TRPV4, HA/PX reduced ROS accumulation in chondrocytes and enhanced [Ca2+]i signaling, reflecting a short-term protection capacity for chondrocytes. In addition, HA/PX balanced the metabolic homeostasis of chondrocytes via TRPV4, including promoting the secretion of type II collagen (Col-II) and aggrecan, the major components of the ECM, and reducing the expression of matrix metal-degrading enzyme (MMP-13), exerting long-term protective effects on chondrocytes. Molecular dynamics (MD) simulations showed that HA/PX could act as a TRPV4 activator. Our results suggest that HA/PX can regulate chondrocyte homeostasis via ROS/Ca2+/TRPV4, thereby improving cartilage regeneration. Because the ECM is a prevalent feature of various cell types, HA/PX holds promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.


Assuntos
Antineoplásicos , Cartilagem Articular , Osteoartrite , Humanos , Condrócitos/metabolismo , Ácido Hialurônico/farmacologia , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Osteoartrite/tratamento farmacológico , Interleucina-1beta/metabolismo , Antineoplásicos/farmacologia , Homeostase , Cartilagem Articular/metabolismo , Células Cultivadas
7.
Sensors (Basel) ; 23(4)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36850757

RESUMO

Machine learning methods can establish complex nonlinear relationships between input and response variables for stadium fire risk assessment. However, the output of machine learning models is considered very difficult due to their complex "black box" structure, which hinders their application in stadium fire risk assessment. The SHapley Additive exPlanations (SHAP) method makes a local approximation to the predictions of any regression or classification model so as to be faithful and interpretable, and assigns significant values (SHAP value) to each input variable for a given prediction. In this study, we designed an indicator attribute threshold interval to classify and quantify different fire risk category data, and then used a random forest model combined with SHAP strategy in order to establish a stadium fire risk assessment model. The main objective is to analyze the impact analysis of each risk characteristic on four different risk assessment models, so as to find the complex nonlinear relationship between risk characteristics and stadium fire risk. This helps managers to be able to make appropriate fire safety management and smart decisions before an incident occurs and in a targeted manner to reduce the incidence of fires. The experimental results show that the established interpretable random forest model provides 83% accuracy, 86% precision, and 85% recall for the stadium fire risk test dataset. The study also shows that the low level of data makes it difficult to identify the range of decision boundaries for Critical mode and Hazardous mode.

8.
Entropy (Basel) ; 25(6)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37372180

RESUMO

Color images have long been used as an important supplementary information to guide the super-resolution of depth maps. However, how to quantitatively measure the guiding effect of color images on depth maps has always been a neglected issue. To solve this problem, inspired by the recent excellent results achieved in color image super-resolution by generative adversarial networks, we propose a depth map super-resolution framework with generative adversarial networks using multiscale attention fusion. Fusion of the color features and depth features at the same scale under the hierarchical fusion attention module effectively measure the guiding effect of the color image on the depth map. The fusion of joint color-depth features at different scales balances the impact of different scale features on the super-resolution of the depth map. The loss function of a generator composed of content loss, adversarial loss, and edge loss helps restore clearer edges of the depth map. Experimental results on different types of benchmark depth map datasets show that the proposed multiscale attention fusion based depth map super-resolution framework has significant subjective and objective improvements over the latest algorithms, verifying the validity and generalization ability of the model.

9.
Anal Chem ; 94(2): 1474-1481, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34984910

RESUMO

In situ imaging of biological indicators is imperative for pathological research by utilizing an activatable photoacoustic (PA) probe. However, precise imaging in actual applications is hampered by the inevitable poor accumulation and low sensitivity. Herein, an amphiphilic molecular probe (AP) was rationally constructed as proof of concept for in situ imaging of drug-induced liver injury, which consists of a hydrophilic target unit and a superoxide anion radical (O2•-)-sensitive small-molecule PA moiety. The probe AP successfully realizes the selectivity and sensitivity toward O2•- in vitro and in living cells. Notably, the amphiphilic probe AP can be selectively retained in the liver and activated toward endogenous O2•- through receptor-mediated endocytosis inside hepatocytes. By virtue of the highly efficient accumulation at the liver, AP was further applied to assess isoniazid-induced liver injury through desired ratiometric PA signals. In addition, based on the fluctuation of O2•-, the therapeutic efficacy of hepatoprotective medicines for hepatotoxicity was analyzed in vivo. Therefore, the O2•--specific probe could serve as a promising molecular tool for early diagnosis study of other liver diseases and analysis of new potential therapeutic agents.


Assuntos
Diagnóstico por Imagem , Hepatócitos , Corantes Fluorescentes , Fígado/diagnóstico por imagem , Sondas Moleculares , Imagem Óptica , Superóxidos
10.
Phys Chem Chem Phys ; 24(28): 17263-17270, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35797730

RESUMO

It has been found that magnetism in two-dimensional (2D) transition metal dichalcogenides can be realized by properly introducing vacancies and applying strain. However, no work has clearly clarified the modulation of such 2D magnetism under a sweeping strain. Thus we were motivated in this work to investigate the mechanical and electronic properties of the monolayer MS2 (M = Mo, W) with symmetric S vacancy defects under sweeping strain. The results show that the local structure of the M atoms in MS2 around the defect undergoes a reversible phase transition from a triangular shape (Tri-3M) with short M-M bonds, to a circular one (Cir-6M-12S) with larger M-M bonds as the planar strain increases. The critical tensile strain for the transition from Tri-3M to Cir-6M-12S are 12.53% for MoS2 and 11.46% for WS2, while the critical compressive strain for the reversal from Cir-6M-12S to Tri-3M are -3.60% and -2.16%, respectively. In particular, we find that the magnetism can be continuously modulated and undergoes a hysteresis loop behavior under the sweeping strains, with the residual magnetism being 2 µB. Our work theoretically predicts the promising prospect for exploring low-dimensional semiconductor spintronic devices working without applying a magnetic field.

11.
Anal Chem ; 93(13): 5420-5429, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33752332

RESUMO

Tumor-specific imaging is a major challenge in clinical tumor resection. To overcome this problem, several activatable probes have been developed for use in tumor imaging. However, most of these probes are activated based on a single-factor stimulation and are irreversible. Therefore, false signals that make tumor-specific imaging difficult are easily generated. We have developed a new dual-stimulus responsive near-infrared (NIR) reversible adenosine 5'-triphosphate (ATP)-pH probe for fluorescence and photoacoustic ratiometric imaging of tumors. Since the H+ and ATP content is significantly higher in the tumor microenvironment than that in normal tissues, the Förster resonance energy transfer-based probe ATP-pH was constructed with silicon rhodamine as the donor, CS dye as the acceptor, and ATP/H+ recognition units that could only be activated when both H+ and ATP were connected to the acceptor. The ATP-pH probe is reversibly activated by both the H+ and ATP, which effectively reduces the cumulative response of the probe in circulation after intravenous injection. Further, the NIR ratiometric property of the probe makes it suitable for in vivo imaging. Finally, our probe was successfully utilized in ratiometric photoacoustic and fluorescence tumor imaging and ratiometric fluorescence imaging-guided tumor resection.


Assuntos
Corantes Fluorescentes , Neoplasias , Transferência Ressonante de Energia de Fluorescência , Humanos , Neoplasias/diagnóstico por imagem , Imagem Óptica , Rodaminas , Microambiente Tumoral
12.
Nano Lett ; 20(4): 2667-2673, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32134674

RESUMO

Layered two-dimensional transition-metal dichalcogenides (2D-TMDs) are promising building blocks for ultracompact optoelectronic applications. Recently, a strong second harmonic generation (SHG) was observed in spiral stacked TMD nanostructures which was explained by its low crystal symmetry. However, the relationship between the efficiency of SHG signals and the electronic band structure remains unclear. Here, we show that the SHG signal in spiral WS2 nanostructures is strongly enhanced (∼100 fold increase) not only when the second harmonic signal is in resonance with the exciton states but also when the excitation energy is slightly above the electronic band gap, which we attribute to a large interband Berry connection associated with certain optical transitions in spiral WS2. The giant SHG enhancement observed and explained in this study could promote the understanding and utility of TMDs as highly efficient nonlinear optical materials and potentially lead to a new pathway to fabricate more efficient optical energy conversion devices.

13.
Sensors (Basel) ; 20(2)2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31968536

RESUMO

Coast-fitting tomographic inversion that is based on function expansion using three types of normal modes (the Dirichlet, Neumann, and open boundary modes) is proposed to reconstruct current fields from the coastal acoustic tomography (CAT) data. The superiority of the method was validated while using CAT data that were obtained in 2015 in the Dalian Bay. The semidiurnal tidal and residual current fields were accurately reconstructed over the entire model domain surrounded by coasts and open boundaries. The proposed method was effective, particularly around the peripheral regions of the tomography domain and the near-coast regions outside the domain, where accurate results are not expected from the conventional inverse method based on function expansion by Fourier function series with no coast fittings. The error velocity for the semidiurnal tidal currents was 2.2 cm s-1, which was calculated from the root-mean-square-difference between the CAT-observed and inverted range-averaged currents that were obtained along the nine peripheral transmission paths. The error velocity for the residual currents estimated from the 12-h mean net residual transport at the bay mouth was 0.9 cm s-1. The errors were significantly smaller than the amplitude of the tidal and residual currents.

14.
Dig Dis Sci ; 64(3): 773-780, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30498928

RESUMO

BACKGROUND: B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses. AIMS: This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice. METHODS: Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBV transgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBV transgenic mice were also analyzed. RESULTS: Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBV transgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBV transgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir. CONCLUSION: HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Diferenciação Celular , Vírus da Hepatite B/genética , Hepatite B/metabolismo , Fígado/metabolismo , Ativação Linfocitária , Células Th17/metabolismo , Animais , Antivirais/farmacologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Guanina/análogos & derivados , Guanina/farmacologia , Hepatite B/imunologia , Hepatite B/prevenção & controle , Hepatite B/virologia , Vírus da Hepatite B/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Interleucina-17/metabolismo , Interleucinas/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/virologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/virologia , Carga Viral , Interleucina 22
15.
Nano Lett ; 18(6): 3885-3892, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29763565

RESUMO

Two-dimensional (2D) layered metal dichalcogenides can form spiral nanostructures by a screw-dislocation-driven mechanism, which leads to changes in crystal symmetry and layer stackings that introduce attractive physical properties different from their bulk and few-layer nanostructures. However, controllable growth of spirals is challenging and their growth mechanisms are poorly understood. Here, we report the controllable growth of WS2 spiral nanoplates with different stackings by a vapor phase deposition route and investigate their formation mechanisms by combining atomic force microscopy with second harmonic generation imaging. Previously not observed "spiral arm" features could be explained as covered dislocation spiral steps, and the number of spiral arms correlates with the number of screw dislocations initiated at the bottom plane. The supersaturation-dependent growth can generate new screw dislocations from the existing layers, or even new layers templated by existing screw dislocations. Different number of dislocations and orientation of new layers result in distinct morphologies, different layer stackings, and more complex nanostructures, such as triangular spiral nanoplates with hexagonal spiral pattern on top. This work provides the understanding and control of dislocation-driven growth of 2D nanostructures. These spiral nanostructures offer diverse candidates for probing the physical properties of layered materials and exploring new applications in functional nanoelectronic and optoelectronic devices.

16.
J Am Chem Soc ; 139(44): 15592-15595, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29058888

RESUMO

Directional growth of ultralong nanowires (NWs) is significant for practical application of large-scale optoelectronic integration. Here, we demonstrate the controlled growth of in-plane directional perovskite CsPbBr3 NWs, induced by graphoepitaxial effect on annealed M-plane sapphire substrates. The wires have a diameter of several hundred nanometers, with lengths up to several millimeters. Microstructure characterization shows that CsPbBr3 NWs are high-quality single crystals, with smooth surfaces and well-defined cross section. The NWs have very strong band-edge photoluminescence (PL) with a long PL lifetime of ∼25 ns and can realize high-quality optical waveguides. Photodetectors constructed on these individual NWs exhibit excellent photoresponse with an ultrahigh responsivity of 4400 A/W and a very fast response speed of 252 µs. This work presents an important step toward scalable growth of high-quality perovskite NWs, which will provide promising opportunities in constructing integrated nanophotonic and optoelectronic systems.

17.
J Gastroenterol Hepatol ; 32(10): 1739-1745, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28183156

RESUMO

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults. METHODS: This study included and followed 3378 initial NAFLD-free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set. RESULTS: Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low-risk group (R ≤ -2.88), moderate-risk group (-2.88 < R ≤ -1.26), and high-risk group (R > -1.26). In the training set, 4.68% of the participants in the low-risk group, 11.59% of the participants in the moderate-risk group, and 31.02% of the participants in the high-risk group developed NAFLD. In the validation set, 5.84% of the participants in the low-risk group, 10.57% of the participants in the moderate-risk group, and 29.44% of the participants in the high-risk group developed NAFLD. CONCLUSIONS: This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects.


Assuntos
Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores Etários , Idade de Início , Idoso , Análise de Variância , Biomarcadores/sangue , Glicemia , Índice de Massa Corporal , Feminino , Previsões , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Risco , Fatores de Tempo , Ultrassonografia
18.
Tohoku J Exp Med ; 242(2): 93-100, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28592717

RESUMO

Aberrant DNA methylation, which can be detected in circulating cell-free DNA (cfDNA), is one of the major epigenetic alterations in hepatocellular carcinoma (HCC). UBE2Q1, a putative member of the ubiquitin-conjugating enzyme family, might play substantial roles in tumorigenesis. However, the methylation status of the UBE2Q1 gene in HCC remains unknown. We aimed to determine the methylation status of the UBE2Q1 gene promoter and to evaluate its potential clinical significance for HCC detection. The methylation-specific polymerase chain reaction (MSP) assay was used to detect the UBE2Q1 gene methylation status in serum samples from 80 patients with hepatitis B virus (HBV)-related HCC, 40 patients with liver cirrhosis (LC), 40 patients with chronic hepatitis B (CHB), and 20 healthy controls (HCs). Significantly lower methylation frequencies were detected in HCC patients (33.75%) compared with LC patients (55.00%, p = 0.026) and CHB patients (60.00%, p = 0.006) and HCs (65.00%, p = 0.011). Hypomethylation of the UBE2Q1 gene was negatively associated with the tumor node metastasis stage (rs = -0.30, p = 0.008). The UBE2Q1 gene methylation status combined with alpha fetoprotein using cut-off points of 20, 200 and 400 ng/ml showed sensitivity and specificity values of 58.8% and 75.0%, 53.8% and 87.5%, and 37.5% and 88.7%, respectively, and yielded a significantly increased area under the ROC curve (0.720, 0.760 and 0.694, respectively) for discriminating HCC from LC and CHB. Our study results suggest that hypomethylation of the UBE2Q1 gene promoter is a potential biomarker for detecting HBV-associated HCC.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Metilação de DNA/genética , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/virologia , Regiões Promotoras Genéticas , Enzimas de Conjugação de Ubiquitina/sangue , Enzimas de Conjugação de Ubiquitina/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Hepatite B Crônica/genética , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , alfa-Fetoproteínas/metabolismo
19.
Rev Esp Enferm Dig ; 109(12): 818-827, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29082740

RESUMO

BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACHBLF) is an acute deteriorating liver disease and rapidly progresses to multiple organ failure. There is currently no adequate accurate predictive models of ACHBLF prognosis. AIMS: To identify the methylation frequency of the estrogen receptor 1 (ESR1) promoter in ACHBLF and analyze the associated prognostic significance. METHODS: Methylation-specific PCR (MSP) was used to determine the methylation frequency of the ESR1 promoter in peripheral blood mononuclear cells from a training and validation cohort of patients. The training cohort included 113 patients with ACHBLF, 73 with chronic hepatitis B (CHB) and 40 healthy controls (HCs). The validation cohort consisted of 37 patients with ACHBLF. Another 18 patients with pre-ACHBLF who progressed to ACHBLF were used to dynamically evaluate ESR1 promoter methylation changes associated with a severe clinical condition. RESULTS: Death from ACHBLF was associated with hyperbilirubinemia, a higher score in the model for end-stage liver disease (MELD), a higher incidence of hepatic encephalopathy (HE) and an increased frequency of ESR1 promoter methylation during the 28 day follow-up. HE, MELD score and ESR1 promoter methylation were the independent risk factors associated with 28-day mortality from ACHBLF. The frequency of ESR1 promoter methylation was significantly higher than in patients with CHB and HCs. Albumin and the MELD score were significantly associated with ESR1 promoter methylation. Moreover, ESR1 promoter methylation frequency increased with ACHBLF progression. More importantly, ESR1 promoter methylation was an independent risk factor and had a high value to predict 28-day mortality from ACHBLF. CONCLUSIONS: Abnormal ESR1 methylation could be a prognostic biomarker for ACHBLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/genética , Receptor alfa de Estrogênio/genética , Hepatite B Crônica/genética , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Estudos de Coortes , Metilação de DNA , Feminino , Hepatite B Crônica/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
20.
Tohoku J Exp Med ; 238(1): 57-64, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26725685

RESUMO

Glutathione-S-transferase P1 (GSTP1) and glutathione-S-transferase M3 (GSTM3) catalyze the glutathione-related clearance of xenobiotics. The methylation of these gene promoters was associated with oxidative stress that induced liver damage. This study aims to explore the relationship among GSTP1 and GSTM3 methylation, DNA methyltransferases (DNMTs) expression, and oxidative stress in patients with chronic hepatitis B (CHB). We retrospectively enrolled 153 patients with CHB and 40 healthy controls (HCs). The GSTP1 and GSTM3 methylation status, DNMTs mRNA levels in peripheral mononuclear cells (PBMCs) and TNF-α and malondialdehyde (MDA) levels in plasma were detected. GSTP1 methylation was significantly higher in patients with CHB than HCs (P = 0.047). Patients with HBeAg-positive CHB showed significantly higher GSTP1 methylation than those with HBeAg-negative CHB (P = 0.017) and HCs (P = 0.007). No significant difference was observed between GSTP1 methylation in HBeAg-negative CHB and HCs (P = 0.191). DNMT1 and DNMT3a mRNA levels were significantly higher in participants with GSTP1 methylation than those without. In patients with CHB, the degree of GSTP1 promoter methylation was significantly correlated with DNMT1 mRNA, DNMT3a mRNA, TNF-α, MDA, HBeAg, ALT, AST and TBIL. In contrast, no significant difference was found between GSTM3 methylation in patients with CHB and HCs (P = 0.079). Meanwhile, no significant difference could be observed between GSTM3 promoter methylation in patients with HBeAg-positive CHB and HBeAg-negative CHB (P = 0.146). Therefore, this study demonstrated that GSTP1 hypermethylation was associated with DNMT1, DNMT3a overexpression and oxidative stress in patients with HBeAg-positive CHB.


Assuntos
Metilação de DNA/genética , Glutationa S-Transferase pi/genética , Hepatite B Crônica/genética , Hepatite B Crônica/patologia , Estresse Oxidativo/genética , Regiões Promotoras Genéticas , Adulto , DNA (Citosina-5-)-Metiltransferases/metabolismo , Feminino , Regulação da Expressão Gênica , Glutationa Transferase/genética , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/enzimologia , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/sangue
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