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1.
Small ; 20(34): e2311821, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38597689

RESUMO

Lithium-air battery (LAB) is regarded as one of the most promising energy storage systems. However, the challenges arising from the lithium metal anode have significantly impeded the progress of LAB development. In this study, cellulose-based filter paper (FP) is utilized as a separator for ambient Li-air batteries to suppress dendrite growth and prevent H2O crossover. Thermogravimetric analysis and molecular spectrum reveal that FP enables ambient Li-air battery operation due to its surface functional groups derived from cellulose. The oxygen-enriched surface of cellulose not only enhances ion conductivity but also captures water and confines solvent molecules, thereby mitigating anode corrosion and side reactions. Compared with commercial glassfiber (GF) separator, this cellulose-based FP separator is cheaper, renewable, and environmentally friendly. Moreover, it requires less electrolyte while achieving prolonged and stable cycle life under real air environment conditions. This work presents a novel approach to realizing practical Li-air batteries by capturing water on the separator's surface. It also provides insights into the exploration and design of separators for enabling practical Li-air batteries toward their commercialization.

2.
Front Oncol ; 14: 1349282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469229

RESUMO

Objective: Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare exocrine tumor of the pancreas. The aim of our study is to summarize the clinical features of SPN and to analyze the risk factors for malignant SPN. Methods: From May 2013 to September 2022, patients who were pathologically confirmed to have SPN were retrospectively reviewed. Demographic data, clinical and pathological features, follow-up data were collected and analyzed. To investigate the factors influencing the benign or malignant nature of SPN, we employed logistic regression. Additionally, we utilized Kaplan-Meier curves to depict and analyze the overall prognosis. Results: A total of 195 patients were included, 163 of whom were female and the average age of all patients was 31.7 years old. Among 195 patients, 101 patients (51.8%) had no obvious clinical symptoms and their pancreatic lesions were detected during routine examination. The primary symptom was abdominal pain and distension in 64 cases (32.8%). The maximum diameter of SPN tumors ranged from 1-17 cm (mean 6.19 cm). Forty-eight postoperative complications developed in 43 (22.1%) patients. After a median follow-up duration of 44.5 months, the overall 5-year survival rate was 98.8% and the recurrence rate was 1.5%. Furthermore, we observed a statistically significant difference in the completeness of the tumor capsule between benign and malignant SPN. Conclusion: SPN is associated with a favorable long-term survival after surgery in our large sample size cohort. For malignant SPN, tumor capsule incompleteness is an independent risk factor.

3.
Aging (Albany NY) ; 15(24): 15267-15286, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38127054

RESUMO

BACKGROUND: Oleanolic acid has important hepatoprotective effects and inhibits liver tissue carcinogenesis. The aim of this study was to investigate the mechanism of action of oleanolic acid in inhibiting liver injury and liver cancer. METHOD: In this study, we applied differential gene analysis and gene enrichment analysis to identify the targets of oleanolic acid for the treatment of liver injury. And this study also applied Cibersort and GSVA methods to investigate the targets of oleanolic acid in liver injury. Based on oleanolic acid targets, we explored the major targets and further explored the role of the major targets in liver cancer. This study used the oncoPredict and the TIDE algorithm to predict the effect of oleanolic acid on drug resistance. Finally, the binding effect of oleanolic acid to relevant targets was explored using molecular docking techniques. RESULT: In this study, oleanolic acid was found to inhibit liver injury and promote liver regeneration mainly by promoting elevated expression of HMOX1. Oleanolic acid can inhibit oxidative stress and promotes Ferroptosis in liver injury. In liver cancer, we identified that the main target of oleanolic acid is HMOX1 and HDAC1. And we determined that HMOX1 promotes Ferroptosis in liver cancer. This reduced the sensitivity of liver cancer to targeted therapies and immunotherapy. Molecular docking showed high binding of oleanolic acid to HDAC1 and HMOX1. CONCLUSIONS: Oleanolic acid is an antioxidant by promoting high expression of HMOX1 and promotes the development of Ferroptosis in liver cancer and liver injury.


Assuntos
Neoplasias Hepáticas , Ácido Oleanólico , Humanos , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Ácido Oleanólico/química , Simulação de Acoplamento Molecular , Transcriptoma , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo
4.
Front Mol Biosci ; 10: 1275791, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908229

RESUMO

Background: Owing to an aging society, there has been an observed increase in the average age of patients diagnosed with hepatocellular carcinoma (HCC). Consequently, this study is centered on identifying the prognostic factors linked with early death among this elderly demographic diagnosed with HCC. Additionally, our focus extends to developing nomograms capable of predicting such outcomes. Methods: The Surveillance, Epidemiology and End Results (SEER) database underpinned this study, showcasing participants aged 75 and above diagnosed with HCC within the timeframe from 2010 to 2015. These participants were divided randomly, at a 7:3 ratio, into training and validation cohorts. Univariable and multivariable logistic regressions were applied to the training cohort in the identification of prognostic indicators of early death, forming the basis for nomogram development. To measure the efficacy of these nomograms within both cohorts, we resorted to Receiver Operating Characteristic (ROC) curves, along with GiViTI calibration belt and Decision Curve Analysis (DCA). Results: The study involved 1,163 elderly individuals diagnosed with HCC, having reported instances of 397 all-cause early deaths and 356 HCC-specific early deaths. The sample group was divided into two cohorts: a training group consisting of 815 individuals, and a validation cohort, comprised of 348 individuals. Multifactorial analysis identified grade, T-stage, surgery, radiation, chemotherapy, bone and lung metastasis as significant predictors of mortality from all causes. Meanwhile, race, grade, T-stage, surgery, radiation, chemotherapy, and bone metastasis were revealed to be estimative factors for cancer-specific mortality. Subsequently, these factors were used to develop nomograms for prediction. GiViTI calibration belt corroborated the acceptable coherence of the nomograms, DCA confirmed their valuable clinical applicability, and ROC curves evidenced satisfactory discriminative capacity within both training and validation cohorts. Conclusion: The nomograms utilized in this study proved instrumental in detecting early death among elderly individuals afflicted with HCC. This tool could potentially assist physicians in formulating individualized treatment strategies.

5.
Neural Netw ; 168: 496-507, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37827068

RESUMO

With the maturity of intelligent technology such as human-computer interaction, human action recognition (HAR) technology has been widely used in virtual reality, video surveillance, and other fields. However, the current video-based HAR methods still cannot fully extract abstract action features, and there is still a lack of action collection and recognition for special personnel such as prisoners and elderly people living alone. To solve the above problems, this paper proposes a multidimensional feature fusion network, called P-MTSC3D, a parallel network based on context modeling and temporal adaptive attention module. It consists of three branches. The first branch serves as the basic network branch, which extracts basic feature information. The second branch consists of a feature pre-extraction layer and two multiscale-convolution-based global context modeling combined squeeze and excitation (MGSE) modules, which can extract spatial and channel features. The third branch consists of two temporal adaptive attention units based on convolution (TAAC) to extract temporal dimension features. In order to verify the validity of the proposed network, this paper conducts experiments on the University of Central Florida (UCF) 101 dataset and the human motion database (HMDB) 51 dataset. The recognition accuracy of the proposed P-MTSC3D network is 97.92% on the UCF101 dataset and 75.59% on the HMDB51 dataset, respectively. The FLOPs of the P-MTSC3D network is 30.85G, and the test time is 2.83 s/16 samples on the UCF101 dataset. The experimental results demonstrate that the P-MTSC3D network has better overall performance than the state-of-the-art networks. In addition, a prison action (PA) dataset is constructed in this paper to verify the application effect of the proposed network in actual scenarios.


Assuntos
Inteligência , Reconhecimento Automatizado de Padrão , Idoso , Humanos , Bases de Dados Factuais , Movimento (Física) , Reconhecimento Psicológico
7.
Opt Express ; 30(8): 13134-13147, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472935

RESUMO

Dental caries is a widespread chronic infectious disease which may induce a series of oral and general problems if untreated. As a result, early diagnosis and follow-up following radiation-free dental caries therapy are critical. Terahertz (THz) waves with highly penetrating and non-ionizing properties are ideally suited for dental caries diagnosis, however related research in this area is still in its infancy. Here, we successfully observe the existence of THz birefringence phenomenon in enamel and demonstrate the feasibility of utilizing THz spectroscopy and birefringence to realize caries diagnosis. By comparing THz responses between healthy teeth and caries, the transmitted THz signals in caries are evidently reduced. Concomitantly, the THz birefringence is also unambiguously inhibited when caries occurs due to the destruction of the internal hydroxyapatite crystal structure. This THz anisotropic activity is position-dependent, which can be qualitatively understood by optical microscopic imaging of dental structures. To increase the accuracy of THz technology in detecting dental caries and stimulate the development of THz caries instruments, the presence of significant THz birefringence effect induced anisotropy in enamel, in combination with the strong THz attenuation at the caries, may be used as a new tool for caries diagnosis.


Assuntos
Cárie Dentária , Espectroscopia Terahertz , Birrefringência , Cárie Dentária/diagnóstico , Humanos , Espectroscopia Terahertz/métodos
8.
Math Biosci Eng ; 18(4): 3667-3679, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198405

RESUMO

The medical image management and analysis system proposed in this paper is a medical software developed by the Browser/Server (B/S) architecture after investigating the workflow of the relevant departments of the hospital, which realizes the entire process of patients from consultation to printing of reports. The computer-aided diagnosis function is added based on image management. Due to the difficulty in collecting medical image data, in the computer-aided diagnosis module, this paper only uses the common fungal keratitis collected from the hospital in the laboratory. Focused microscope images are used for experiments. First, the images were trained with three convolutional neural networks, AlexNet, ZFNet, and VGG16. These models which classify fungal keratitis were obtained and integrated was performed to obtain better classification results. Finally, the model was integrated with the system designed in this paper, which realized the automatic diagnosis of Confocal Microscopy (CM) images of fungal keratitis online and provided it to medical staff for reference. The system can improve the work efficiency of the image-related departments while reducing the workload of doctors in the department to manually read the films.


Assuntos
Processamento de Imagem Assistida por Computador , Ceratite , Diagnóstico por Computador , Humanos , Ceratite/diagnóstico por imagem , Redes Neurais de Computação , Software
9.
Front Psychol ; 12: 627443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935878

RESUMO

This study examined the relationships between the role of the instructor and university students' learning outcomes in cloud-based classrooms during the COVID-19 (coronavirus disease 2019) pandemic. The results of an online survey of 7,210 university students in mainland China revealed that the students' perceived learning outcomes and learning satisfaction were positively related to instructor innovation and negatively related to instructor performance. Instructional support was positively related to the students' perceived learning outcomes but not directly related to their learning satisfaction. The students' academic self-efficacy mediated the influence of instructional support and instructor innovation on their perceived learning outcomes and learning satisfaction. The results contribute to knowledge of the role instructors play in facilitating students' learning outcomes in higher education and suggest ways to improve the learning environment and learning outcomes, especially in cloud-based virtual classrooms.

10.
Math Biosci Eng ; 18(2): 968-982, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33757169

RESUMO

As the number of various sensors grows fast in real applications such as smart city and intelligent agriculture, context-aware systems would acquire raw context information from dynamic, asynchronous and heterogeneous context providers, but multi-source information usually leads to the situation uncertainty of the system entities involved, which is harmful to appropriate services, and specially the inconsistency is a kind of main uncertainty problems and should be processed properly. A new inconsistent context fusion algorithm based on back propagation (BP) neural network and modified Dempster-Shafer theory (DST) combination rule is proposed in this paper to eliminate the inconsistency to the greatest extent and obtain accurate recognition results. Through the BP neural network, the situations of entities can be recognized effectively, and based on the modified combination rule, the recognition results can be fused legitimately and meaningfully. In order to verify the performance of the proposed algorithm, several experiments under different error rates of context information sources are conducted in the personal identity verification (PIV) application scenario. The experimental results show that the proposed BP neural network and modified DST based inconsistent context fusion algorithm can obtain good performance in most cases.

11.
Sensors (Basel) ; 21(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467431

RESUMO

A new algorithm based on singular value decomposition (SVD) to remove cardiac contamination from trunk electromyography (EMG) is proposed. Its performance is compared to currently available algorithms at different signal-to-noise ratios (SNRs). The algorithm is applied on individual channels. An experimental calibration curve to adjust the number of SVD components to the SNR (0-20 dB) is proposed. A synthetic dataset is generated by the combination of electrocardiography (ECG) and EMG to establish a ground truth reference for validation. The performance is compared with state-of-the-art algorithms: gating, high-pass filtering, template subtraction (TS), and independent component analysis (ICA). Its applicability on real data is investigated in an illustrative diaphragm EMG of a patient with sleep apnea. The SVD-based algorithm outperforms existing methods in reconstructing trunk EMG. It is superior to the others in the time (relative mean squared error < 15%) and frequency (shift in mean frequency < 1 Hz) domains. Its feasibility is proven on diaphragm EMG, which shows a better agreement with the respiratory cycle (correlation coefficient = 0.81, p-value < 0.01) compared with TS and ICA. Its application on real data is promising to non-obtrusively estimate respiratory effort for sleep-related breathing disorders. The algorithm is not limited to the need for additional reference ECG, increasing its applicability in clinical practice.


Assuntos
Algoritmos , Eletrocardiografia , Eletromiografia , Processamento de Sinais Assistido por Computador , Humanos , Razão Sinal-Ruído , Tronco
12.
Medicine (Baltimore) ; 99(50): e23271, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327249

RESUMO

BACKGROUND: Mixed neuroendocrine nonneuroendocrine neoplasms (MiNENs) originating from the biliary system (gallbladder, biliary tract, or ampulla of Vater) are extremely rare and have not been discussed in detail or systematically. We aimed to present the demographics, clinicopathological characteristics, management, and prognostic factors of biliary MiNENs. METHODS: A systematic search of electronic biomedical databases (Web of Science, PUBMED, and Embase) was performed to identify eligible studies. Survival was analyzed with the Kaplan-Meier method. Log-rank tests were used to evaluate the differences between groups, and the effects of various clinical and histopathological features on prognosis were analyzed by univariate and multivariate Cox regression. RESULTS: Fifty-three publications (patients, n = 67) were included. The median overall survival time was 21.0 months. Fifty-one patients (76.1%) underwent radical surgery and median survival for 41 months (P < .001). Twenty-two patients who received adjuvant radiochemotherapy treatment after radical surgery had a median survival for 43 months (P = .076). Radical resection (P < .001), Ki-67 index (P = .011), tumor stage (P < .001), neuroendocrine (NEC) grade (P = .011), and non-NEC grade (P = .017) were independent statistically significant prognostic factors according to univariate analysis; radical resection (P = .010) and small morphological subtype (P = .036) were independent statistically significant prognostic factors associated with higher overall survival according to multivariate analysis, and radical resection (P = .005) and age < 65 years (P = .026) were associated with higher recurrence free survival time. CONCLUSION: Radical resection is essential for long-term survival. Aggressive multimodality therapy with adjuvant radiochemotherapy and biotherapy may improve survival of biliary MiNENs. Further randomized controlled trials are needed to determine the standard treatment.


Assuntos
Neoplasias do Sistema Biliar/patologia , Carcinoma Neuroendócrino/patologia , Tumor Misto Maligno/patologia , Tumores Neuroendócrinos/patologia , Sistema Biliar/patologia , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias do Sistema Biliar/terapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Humanos , Tumor Misto Maligno/diagnóstico , Tumor Misto Maligno/terapia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Prognóstico , Análise de Sobrevida
13.
Diagnostics (Basel) ; 10(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32887436

RESUMO

BACKGROUND: Biliary strictures are frequently encountered in clinical practice. The determination of their nature is often difficult. This study aims to systematically evaluate the efficacy and safety of the second generation of digital single-operator cholangioscopy (SpyGlass DS, DSOC) in indeterminate biliary strictures (IBDS) through biopsies. METHODS: All relative studies published in Medline, the Cochrane Library, Web of Science, and EMBASE were included. The diagnostic tests for IBDS were compared to the surgical histology, autopsy, or long-term clinical follow-up. The methodological quality of the included studies was evaluated by the Quality Assessment of Studies of Diagnostic Accuracy Included in Systematic Reviews (QUADAS-2). RESULTS: A total of 11 studies, which involved 356 patients diagnosed through biopsies, were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.74 (95% CI: 0.67-0.80), 0.98 (95% CI: 0.95-1.00), 10.52 (95% CI: 5.45-20.32), 0.31 (95% CI: 0.23-0.41), and 65.18 (95% CI: 26.79-158.61), respectively. The area under the curve (AUC) was 0.9479, and the pooled adverse event rate was 7%. The sensitivity and specificity in the heterogeneity analysis were I2 = 48.1% and I2 = 25.4%, respectively. CONCLUSION: SpyGlass DS is a safe and effective technique for IBDS. However, future randomized trials are needed to determine optimal number of biopsies.

14.
Cancer Lett ; 478: 22-33, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32067991

RESUMO

The introduction of long non-coding RNAs (lncRNAs) has revolutionized the treatment of hepatocellular carcinoma (HCC). Thus, in the present study, we aimed to evaluate the effect of a newly found lncRNA, LINC00160, on autophagy and drug resistance of HCC. Interaction among LINC00160, miR-132 and PIK3R3 was verified by dual luciferase reporter gene assay. Loss- and gain-of function experiments were conducted in HCC cells to explore the roles of LINC00160, miR-132 and PIK3R3 in HCC by determining cell viability, autophagy and apoptosis. Finally, tumorigenicity in nude mice was established to confirm the in vitro findings. LINC00160 and PIK3R3 were up-regulated but miR-132 was down-regulated in HCC tissues and cells. LINC00160 may regulate miR-132 and PIK3R3 was the target gene of miR-132. LINC00160 increased the expression of LC3I/LC3II and Atg5 but decreased the p62 expression, while silencing of LINC00160 or over-expression of miR-132 suppressed HCC cell viability, autophagy, drug-resistance and tumorigenicity in nude mice but promoted HCC cell apoptosis by inhibiting the PIK3R3 expression. Taken together, silencing of LINC00160 suppresses autophagy and drug resistance in HCC by regulating miR-132-targeted PIK3R3.


Assuntos
Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , RNA Longo não Codificante/genética , Idoso , Animais , Autofagia , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias
15.
J Cell Biochem ; 120(12): 19775-19783, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31310393

RESUMO

Small nucleolar RNA host gene 15 (SNHG15) is a long noncoding RNA (lncRNA), which promotes progression of multiple cancers. Its specific function in hepatocellular carcinoma (HCC), however, is uncertain. The aims of our study were, therefore, to explore the role of SNHG15 in HCC. SNHG15 and miR-141-3p expression were assessed via quantitative real-time PCR (qRT-PCR) in 58 paired HCC samples and adjacent matched adjacent normal tissues. CCK-8 assay, flow cytometric examination, and wound healing/invasion assays were used to respectively assess how SNHG15 influences cell proliferation, the cell cycle, and the migratory and invasive potential of HCC cells. MicroRNA (miRNAs) that targeted SNHG15 was screened by Starbase2.0 and identified by RNA immunoprecipitation and luciferase reporter assays. SNHG15 expression was markedly increased, whereas miR-141-3p expression was substantially reduced in HCC cells and tissue samples relative to normal controls. When SNHG15 was knocked down, this resulted in a significant disruption to the proliferation, as well as the invasive and migratory ability of these HCC cells. miR-141-3p was also found to be an SNHG15 target in HCC cells. Furthermore, miR-141-3p inhibitor partially reversed the observed SNHG15 depletion-mediated reduction in HCC proliferation, migration, and invasion. By repressing miR-141-3p, SNHG15 could modulate zinc finger E-box binding homeobox 2 (ZEB2) and E2F transcription factor 3 (E2F3) expression, both of which are miR-141-3p targets. These finding suggested that SNHG15 promoted HCC progression via negative regulation of miR-141-3p, thus identifying a potential novel HCC treatment pathway.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Fator de Transcrição E2F3/genética , Fator de Transcrição E2F3/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/patologia , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
16.
Sensors (Basel) ; 17(6)2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28587085

RESUMO

With the rapid development of wireless communication systems and electronic techniques, the limited frequency spectrum resources are shared with various wireless devices, leading to a crowded and challenging coexistence circumstance. Cognitive radio (CR) and ultra-wide band (UWB), as sophisticated wireless techniques, have been considered as significant solutions to solve the harmonious coexistence issues. UWB wireless sensors can share the spectrum with primary user (PU) systems without harmful interference. The in-band interference of UWB systems should be considered because such interference can severely affect the transmissions of UWB wireless systems. In order to solve the in-band interference issues for UWB wireless sensor networks (WSN), a novel in-band narrow band interferences (NBIs) elimination scheme is proposed in this paper. The proposed narrow band interferences suppression scheme is based on a novel complex-coefficient adaptive notch filter unit with a single constrained zero-pole pair. Moreover, in order to reduce the computation complexity of the proposed scheme, an adaptive complex-coefficient iterative method based on two-order Taylor series is designed. To cope with multiple narrow band interferences, a linear cascaded high order adaptive filter and a cyclic cascaded high order matrix adaptive filter (CCHOMAF) interference suppression algorithm based on the basic adaptive notch filter unit are also presented. The theoretical analysis and numerical simulation results indicate that the proposed CCHOMAF algorithm can achieve better performance in terms of average bit error rate for UWB WSNs. The proposed in-band NBIs elimination scheme can significantly improve the reception performance of low-cost and low-power UWB wireless systems.

17.
Chem Commun (Camb) ; 53(38): 5294-5297, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28443856

RESUMO

The fabrication of advanced hierarchical porous polymers with a unique 3D nanonetwork structure composed of functional core-microporous shell nanoparticles was reported based on the development of a simple and efficient hypercrosslinking-induced self-assembly strategy.

18.
Free Radic Res ; 39(4): 373-81, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16032782

RESUMO

It has been implicated that reactive oxygen species (ROS) play important roles in modulating tumor progression. However, the mechanisms by which redox-regulated tumor progression are largely unknown. We previously demonstrated that reduced intracellular redox conditions could be achieved in stably transfected small cell lung cancer cells with gamma-glutamylcysteine synthetase (gamma-GCSh) cDNA which encodes a rate-limiting enzyme in the biosynthesis of glutathione (GSH), a major physiological redox regulator. In the present study, using DNA microarray analyses, we compared the expression profiles between the gamma-GCSh-transfected cells and their nontransfected counterpart. We observed downregulation of several matrix metalloproteinases (MMPs), i.e., MMPI and MMP3, and MMP10 in the transfected cells. Dot blot and Northern blot hybridizations confirmed that, among the 18 MMP gene family members and four tissue inhibitors of matrix metalloprotein family (TIMP) analyzed, the expression levels of these three MMPs were consistently reduced. Transiently increased gamma-GCSh expression using tetracycline-inducible gamma-GCSh adenoviral expression system also showed down-regulation of MMP3 and MMP10, but not MMP1. Our results demonstrated that redox regulation of MMP1, MMP3 and MMP10 expression depend upon different modes of redox manipulation. These results bear implication that antioxidant modulation of antitumor progression may be contributed at least in part by the downregulation of a subset of metrix metalloproteins.


Assuntos
Carcinoma de Células Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Metaloproteinases da Matriz/metabolismo , Oxirredução , Northern Blotting , Western Blotting , Linhagem Celular Tumoral , Expressão Gênica , Perfilação da Expressão Gênica , Glutamato-Cisteína Ligase/biossíntese , Glutamato-Cisteína Ligase/genética , Glutationa/biossíntese , Humanos , Immunoblotting , Metaloproteinases da Matriz/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/análise , Espécies Reativas de Oxigênio/metabolismo , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo , Transfecção
19.
J Biol Chem ; 279(49): 51075-81, 2004 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-15466414

RESUMO

The c-Jun N-terminal kinase (JNK)/stress activated protein kinase is preferentially activated by stress stimuli. Growth factors, particularly ligands for G protein-coupled receptors, usually induce only modest JNK activation, although they may trigger marked activation of the related extracellular signal-regulated kinase. In the present study, we demonstrated that homozygous disruption of glycogen synthase kinase 3beta (GSK-3beta) dramatically sensitized mouse embryonic fibroblasts (MEFs) to JNK activation induced by lysophosphatidic acid (LPA) and sphingosine-1-phosphate, two prototype ligands for G protein-coupled receptors. To a lesser degree, a lack of GSK-3beta also potentiated JNK activation in response to epidermal growth factor. In contrast, the absence of GSK-3beta decreased UV light-induced JNK activation. The increased JNK activation induced by LPA in GSK-3beta null MEFs was insufficient to trigger apoptotic cell death or growth inhibition. Instead, the increased JNK activation observed in GSK-3beta-/- MEFs was associated with an increased proliferative response to LPA, which was reduced by the inhibition of JNK. Ectopic expression of GSK-3beta in GSK-3beta-negative MEFs restrained LPA-triggered JNK phosphorylation and induced a concomitant decrease in the mitogenic response to LPA compatible with GSK-3beta through the inhibition of JNK activation, thus limiting LPA-induced cell proliferation. Mutation analysis indicated that GSK-3beta kinase activity was required for GSK-3beta to optimally inhibit LPA-stimulated JNK activation. Thus GSK-3beta serves as a physiological switch to specifically repress JNK activation in response to LPA, sphingosine-1-phosphate, or the epidermal growth factor. These results reveal a novel role for GSK-3beta in signal transduction and cellular responses to growth factors.


Assuntos
Quinase 3 da Glicogênio Sintase/fisiologia , Substâncias de Crescimento/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Esfingosina/análogos & derivados , Células 3T3 , Animais , Apoptose , Western Blotting , Células Cultivadas , Citoplasma/metabolismo , Análise Mutacional de DNA , Relação Dose-Resposta a Droga , Ativação Enzimática , Fator de Crescimento Epidérmico/metabolismo , Fibroblastos/metabolismo , Vetores Genéticos , Quinase 3 da Glicogênio Sintase/química , Glicogênio Sintase Quinase 3 beta , Homozigoto , Ligantes , Cloreto de Lítio/farmacologia , Lisofosfolipídeos/metabolismo , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mutação , Fosforilação , Propídio/farmacologia , Estrutura Terciária de Proteína , Retroviridae/genética , Transdução de Sinais , Esfingosina/metabolismo , Timidina/química , Fatores de Tempo , Raios Ultravioleta
20.
Cancer Biol Ther ; 3(3): 340-7, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14726688

RESUMO

Programmed cell death and survival are controlled by complex pathways, with the anti-apoptotic proteins Bcl-2 and Bcl-X(L) and the pro-apoptotic proteins Bax and Bcl-X(S) being major regulators. Variations in the expression of Bcl-X(S) have been observed in leukemic cells from acute myeloid leukemia (AML) patients and correlated with clinical outcome, but the impact of Bcl-X(S) on molecular pathophysiological mechanisms and the potential role of Bcl-X(S) as a therapeutic target in AML are not yet defined. In order to analyze the functional relevance of Bcl-X(S) in AML, Bcl-X(S) was moderately (2-3 fold) overexpressed in the AML cell lines HL-60 and MO7e by transfection with a tetracycline-regulatable Bcl-X(S) expression system. Increased Bcl-X(S) did not change the rate of spontaneous apoptosis, chemosensitivity to ara-C, or cell cycle kinetics. Further analysis of this unexpected result revealed a compensatory transcriptional upregulation of endogenous anti-apoptotic Bcl-X(L) in MO7e and HL-60, and Bcl-2 in HL-60 cells resulting in increased protein levels. Bax levels were unchanged. Bcl-X(L) and Bcl-2 were found to heterodimerize with Bcl-X(S), thereby providing a possible explanation for the abrogation of its pro-apoptotic function. These results suggest the existence of a regulatory mechanism aimed to protect leukemic cells from pro-apoptotic stimuli.


Assuntos
Apoptose , Leucemia Mieloide/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Doença Aguda , Antimetabólitos Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Citarabina/farmacologia , Células HL-60 , Humanos , Células Tumorais Cultivadas , Regulação para Cima , Proteína bcl-X
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