RESUMO
The exact role of VD deficiency in the development of non-alcoholic fatty liver disease (NAFLD) remains unknown. In this study, we induced VD deficiency by feeding Female Sprague-Dawley rats a VD deficient (VDD) Diet and studied the hepatic changes associated with VD deficiency. Simultaneously, we provided the VDD rats with VD or 8-methoxy psoralen (8-MOP), a suggested vitamin D receptor agonist, to test the reversibility of the hepatic changes. VDD Rats developed borderline non-alcoholic steatohepatitis (NASH) with considerable elevation in hepatic triglycerides, total cholesterol, and malondialdehyde. Furthermore, VD deficiency induced the expression of crucial enzymes and transcription factors involved in denovo lipogenesis, which justified the hepatic lipid accumulation. Insulin receptor signaling was affected by VD deficiency, demonstrated by the elevation in insulin substrate-1 (IRS1) and reduction in insulin substrate-2 (IRS2) signaling. Treatment with VD or 8-MOP attenuated IRS1 signaling and its downstream targets, leading to a decline in de novo lipogenesis, while the elevation in IRS2 expression resulted in the nuclear exclusion of forkhead box O1 (FoxO1) and diminished gluconeogenesis, a vital source of acetyl-CoA for de novo lipogenesis. Moreover, 8-MOP and Calcipotriol modulated insulin signaling in human hepatocyte cell line L02, which highlighted the crucial role of VD in the regulation of hepatic lipid contents in rats and humans. Silencing of the vitamin D receptor expression in L02 diminished the inhibitory effect of Calcipotriol and 8-MOP on fatty acid synthase and acetyl- CoA carboxylase 1 and provided the evidence that 8-MOP actions mediated via vitamin D receptor.
Assuntos
Proteínas Substratos do Receptor de Insulina/metabolismo , Metoxaleno/farmacologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Deficiência de Vitamina D/complicações , Ração Animal , Animais , Calcitriol/administração & dosagem , Calcitriol/análogos & derivados , Linhagem Celular , Feminino , Técnicas de Silenciamento de Genes , Gluconeogênese , Humanos , Insulina/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Metoxaleno/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Deficiência de Vitamina D/metabolismoRESUMO
Background and purpose: Adaptive radiotherapy (ART) can compensate for the dosimetric impacts induced by anatomic and geometric variations in patients with nasopharyngeal carcinoma (NPC); Yet, the need for ART can only be assessed during the radiation treatment and the implementation of ART is resource intensive. Therefore, we aimed to determine tumoral biomarkers using pre-treatment MR images for predicting ART eligibility in NPC patients prior to the start of treatment. Methods: Seventy patients with biopsy-proven NPC (Stage II-IVB) in 2015 were enrolled into this retrospective study. Pre-treatment contrast-enhanced T1-w (CET1-w), T2-w MR images were processed and filtered using Laplacian of Gaussian (LoG) filter before radiomic features extraction. A total of 479 radiomics features, including the first-order (n = 90), shape (n = 14), and texture features (n = 375), were initially extracted from Gross-Tumor-Volume of primary tumor (GTVnp) using CET1-w, T2-w MR images. Patients were randomly divided into a training set (n = 51) and testing set (n = 19). The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for radiomic model construction in training set to select the most predictive features to predict patients who were replanned and assessed in the testing set. A double cross-validation approach of 100 resampled iterations with 3-fold nested cross-validation was employed in LASSO during model construction. The predictive performance of each model was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC). Results: In the present cohort, 13 of 70 patients (18.6%) underwent ART. Average AUCs in training and testing sets were 0.962 (95%CI: 0.961-0.963) and 0.852 (95%CI: 0.847-0.857) with 8 selected features for CET1-w model; 0.895 (95%CI: 0.893-0.896) and 0.750 (95%CI: 0.745-0.755) with 6 selected features for T2-w model; and 0.984 (95%CI: 0.983-0.984) and 0.930 (95%CI: 0.928-0.933) with 6 selected features for joint T1-T2 model, respectively. In general, the joint T1-T2 model outperformed either CET1-w or T2-w model alone. Conclusions: Our study successfully showed promising capability of MRI-based radiomics features for pre-treatment identification of ART eligibility in NPC patients.
RESUMO
This paper presents a real-time motion planning approach for autonomous vehicles with complex dynamics and state uncertainty. The approach is motivated by the motion planning problem for autonomous vehicles navigating in GPS-denied dynamic environments, which involves non-linear and/or non-holonomic vehicle dynamics, incomplete state estimates, and constraints imposed by uncertain and cluttered environments. To address the above motion planning problem, we propose an extension of the closed-loop rapid belief trees, the closed-loop random belief trees (CL-RBT), which incorporates predictions of the position estimation uncertainty, using a factored form of the covariance provided by the Kalman filter-based estimator. The proposed motion planner operates by incrementally constructing a tree of dynamically feasible trajectories using the closed-loop prediction, while selecting candidate paths with low uncertainty using efficient covariance update and propagation. The algorithm can operate in real-time, continuously providing the controller with feasible paths for execution, enabling the vehicle to account for dynamic and uncertain environments. Simulation results demonstrate that the proposed approach can generate feasible trajectories that reduce the state estimation uncertainty, while handling complex vehicle dynamics and environment constraints.
RESUMO
OBJECTIVE: The aim of this study was to explore the expression of DLC-l in breast carcinoma and any association with tumor metastasis. METHODS: 51 surgical specimens of human breast carcinoma, divided into high invasive and low invasive groups according to their clinicopathological features, 30 cases of adjacent normal tissue and 28 benign breast lesions were examined by qRT-PCR for expression of DLC-1. RESULTS: Expression level of DLC-1 in adjacent normal tissue and benign breast lesion specimens was higher than that in breast carcinoma (P<0.0001); the values in the high invasive group with synchronous metastases were also lower than in the low invasive group (P=0.0275). The correlation between DLC-1 expression level and tumor progression and metastasis of breast cancer was negative. CONCLUSION: As an anti-oncogene, DLC-1 could play an important part in breast carcinoma occurrence, progression, invasiveness and metastasis. Detecting the changes of the expression of DLC-1 in the breast carcinoma may contribute to earlier auxiliary diagnosis of invasiveness, metastasis and recrudescence.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Carcinoma/patologia , Proteínas Ativadoras de GTPase/genética , Expressão Gênica , Proteínas Supressoras de Tumor/genética , Mama/metabolismo , Doenças Mamárias/genética , Doenças Mamárias/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Progressão da Doença , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Invasividade Neoplásica , Metástase Neoplásica , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas , Proteínas Supressoras de Tumor/metabolismoRESUMO
The aim of the present research was to investigate clinicopathologic correlations of immunohistochemically- demonstrated axin (axis inhibition) and ß-catenin expression in primary hepatocellular carcinomas (HCCs), in comparison with paraneoplastic, cirrhotic and normal liver tissues. Variation in Axin expression across groups were significant (P < 0.01), correlating with alpha fetoprotein (AFP), HBsAg, cancer plugs in the portal vein, and clinical stage of HCCs(P < 0.05); however, there were no links with sex, age, and tumour size (P > 0.05). Differences in cell membrane ß-catenin expression were also statistically significant (P < 0.01), again correlated with AFP, HBsAg, cancer plugs in the portal vein, and clinical stage in HCCs (P < 0.05) but not with sex, age, and tumour size (P > 0.05). Axin expression levels in tissues with reduced membrane ß-catenin were low (P < 0.05), also being low with nuclear ß-catenin expression (P < 0.05). Axin and ß-catenin may play an important role in the genesis and progression of HCC via the Wnt signal transmission pathway. Simultaneous determination of axin, ß-catenin, AFP, and HBsAg may be useful for early diagnosis, and metastatic and clinical staging of HCCs.
Assuntos
Proteína Axina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , beta Catenina/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/secundário , Estudos de Casos e Controles , Membrana Celular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Antígenos de Superfície da Hepatite B/metabolismo , Humanos , Técnicas Imunoenzimáticas , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Veia Porta/metabolismo , Veia Porta/patologia , Prognóstico , alfa-Fetoproteínas/metabolismoRESUMO
Under different temperatures and physiological conditions, with cefuroxime axetil concentrations in the range of 1.959 X 10(-6) to 13.71 X 10(-6) mol x L(-1), and bovine serum albumin (BSA) concentrations at 2.0 X 10(-6) mol x L(-1), the interaction between cefuroxime axetil and BSA was studied by fluorescence spectroscopy, three-dimensional fluorescence spectrum, synchronous fluorescence spectrum and UV-Vis absorption spectroscopy. After analyzing and processing the fluorescence quenching data at different temperatures according to Sterm-Volmer equation, Lineweaver-Burk equation and thermodynamic equation, the average value of the apparent binding constant (K(LB): 3.907 X 10(6) L x mol(-1)), and thermodynamics parameters (enthalpy change delta H: -13.43 kJ x mol(-1), entropy change delta S: 81.90 J x K(-1) and standard Gibbs free energy change delta G0: -38.34 kJ x mol(-1)) were calculated, and the amounts of binding sites (n: 1.042)were measured. The fluorescence quenching mechanism of BSA after cefuroxime axetil was added was discussed. BSA was bound with cefuroxime axetil and formed a new compound. The quenching belonged to static fluorescence quenching. The thermodynamic parameters agree with delta H approximately 0, delta S > 0 and delta G0 < 0, and the binding reaction is mainly entropy-driven and electro-static interaction force plays a major role in the reaction. The maximum emission wavelength of Tyr and Trp had an obvious red shift in the synchronous fluorescence spectra, the fluorescence emission wavelength of two peaks had a blue shift in the three-dimensional fluorescence spectrum of BSA in the presence of cefuroxime axetil and the maximum absorbtion wavelenghs of three systems in the UV-Vis absorption spectra were obviously different. These showed that the changes in the micro-environment of Tyr and Trp and demonstrated that the conformation of BSA changed as cefuroxime axetil had been added. This provides important information for discussing the configuration modification of BSA because of the added cefuroxime axetil, and for elucidating the pharmacological effects of cefuroxime axetil and biological effects in the organism.
Assuntos
Antibacterianos/química , Cefuroxima/análogos & derivados , Soroalbumina Bovina/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Termodinâmica , Absorção , Animais , Antibacterianos/análise , Bovinos , Cefuroxima/análise , Cefuroxima/química , Entropia , Estrutura Molecular , Ligação Proteica , Conformação Proteica , Soroalbumina Bovina/análise , TemperaturaRESUMO
At different temperatures, the binding of naphthol green B (NGB) to bovine serum albumin (BSA) was studied by the fluorescence spectroscopy, three-dimensional fluorescence spectrum, synchronous fluorescence spectrum and ultra-violet spectrum. It was shown that this compound has a quite strong ability to quench the fluorescence from BSA. After analyzing the fluorescence quenching data according to Sterm-Volmer equation and Lineweaver-Burk equation, it was found that BSA had reacted with naphthol green B and formed a new compound, the quenching action was due to static fluorescence quenching, and the action force was electrostatic interaction. According to the Lineweaver-Burk equation and thermodynamic equation, the average value of the binding constant (KLe: 1.411 x 10(5) L x mol(-1)), the thermodynamic parameters (DeltaHtheta: -5.707 kJ x mol(-1), DeltaGtheta: -30.25 kJ x mol(-1) and DeltaStheta: 79.95 J x K(-1)) and the amounts of binding sites (1.258) were obtained, providing important information for the research on the configuration modification of BSA because of the added naphthol green B, biological effects in a living body, and the coloration mechanism of naphthol green B.
Assuntos
Corantes/química , Compostos Férricos/química , Naftalenossulfonatos/química , Naftóis/química , Soroalbumina Bovina/química , Animais , Bovinos , Ligação Proteica , Espectrometria de FluorescênciaRESUMO
The interaction of tricyclazole (TCZ) with beta-cyclodextrin (beta-CD) and human serum albumin (HSA) were studied by fluorescence spectrum, UV-visible spectrum and second-order scattering technology. It was shown that TCZ has quite a strong ability to quench the fluorescence launching from HSA by reacting with it and forming a certain kind of new compound. The quenching and the energy transfer mechanisms were discussed, respectively. The binding constants and thermodynamic parameters at four different temperatures, the binding locality, and the binding power were obtained. The conformation of HSA was discussed by synchronous and three-dimensional fluorescence techniques. The inclusion reaction between beta-CD and TCZ was explored by scattering method, the inclusion constants and the thermodynamic parameters at 297 K and 311 K were figured out, respectively. The mechanism of inclusion reaction was speculated and linkage among the toxicity of TCZ, the exterior environment and its concentration was attempted to explain on molecule level.
Assuntos
Albumina Sérica/metabolismo , Espectrometria de Fluorescência/métodos , Tiazóis/química , beta-Ciclodextrinas/química , Interações Medicamentosas , Transferência de Energia , Fluorescência , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Ligação Proteica , Espectrofotometria Ultravioleta , Termodinâmica , Tiazóis/metabolismo , beta-Ciclodextrinas/metabolismoRESUMO
OBJECTIVE: To study the effects of Yanshu injection on the combined treatment in the advanced primary liver cancer. METHOD: Eighty-five cases of advanced primary liver cancer were treated with Yanshu injection combining with chemotherapy or only chemotherapy. The curative effects, pain genesic rate, one year survival rate, survival quality of life and cell immune functions were observed. RESULT: The remission rate and one year survival rate of the trial group were 60.5% and 51.2%, respectively, and were significantly higher than those (45.2% and 40.5%) of the control group (P < 0.05). The pain relief rate of the trial group was significantly higher than that of the control group (P < 0.05). The improvement of the quality of life was higher than that of the contral group (P < 0.01). The ability of the T-cell subgroup and NK-cell of the trail group were significantly difference between pre-and post-treatment (P < 0.01 or 0.05); however, that of the control group was no obviously change. CONCLUSION: Yanshu injection combination with chemotherapy can raise the curative effect, one year survival rate and cellular immune function, reduce pain genesic rate and toxicity of chemotherapy, and improve the quality of life of the patients with advanced primary liver cancer, which is worthy to be recommended for clinical application.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Fitoterapia , Sophora , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Humanos , Injeções Intravenosas , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Plantas Medicinais/química , Qualidade de Vida , Sophora/química , Taxa de SobrevidaRESUMO
The binding of eosin Y to bovine serum albumin (BSA) was studied by fluorescence spectroscopy and ultraviolet spectrum. It was shown that this compound has a quite strong ability to quench the fluorescence from BSA. After analyzing the fluorescence quenching data according to Sterm-Volmer equation, Lineweaver-Burk equation and thermodynamic equation at 298. 15 K, the binding constant(KLB= 3. 601 x 10(5) L x mol(-1)) and thermodynamic parameters (deltaHtheta: - 22. 66 kJ x mol(-1), deltaGtheta: -31. 30 kJ x mol(-1) and deltaStheta: 36.32 J x K(-1)were obtained, which provide important information for researching the configuration modification of BSA caused by added eosin Y, biological effects of eosin Y in a living body, and dyeing mechanism of cells.
Assuntos
Amarelo de Eosina-(YS)/química , Soroalbumina Bovina/química , Animais , Bovinos , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , TermodinâmicaRESUMO
The binding of newly compounded perseleno diphenyl 2,2'-diformic acid to bovine serum albumin(BSA) was studied at different temperatures using fluorescence spectrum and UV spectrum. The fluorescence quenching data was analyzed according to Stern-Volmer equation and Lineweaver-Burk double-reciprocal equation. It was showed that this quenching complies better with the charactristic of static fluorescence quenching. The binding constant, thermodynamic parameters, and the binding spot of the compound with certain structure, coming from perseleno diphenyl 2,2'-diformic acid and bovine serum albumin, were obtained. Besides, themechanism of static fluorescence quenching and the quality of binding power were both discussed. The information of the binding mode, the mechanism of its transportation, and some medical theories in human body were offered.
Assuntos
Compostos Organometálicos/química , Compostos Organosselênicos/química , Selênio/química , Soroalbumina Bovina/química , Termodinâmica , Algoritmos , Animais , Bovinos , Fluorescência , Humanos , Cinética , Modelos Químicos , Estrutura Molecular , Compostos Organometálicos/metabolismo , Compostos Organosselênicos/metabolismo , Ligação Proteica , Soroalbumina Bovina/metabolismo , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , TemperaturaRESUMO
The binding feature of dipyridamole with bovine serum albumin (BSA) was studied using fluorescence spectroscopy. It was shown that this compound has a powerful ability to quench the BSA fluorescence via a nonradiative energy transfer mechanism. The fluorescence quenching data were analyzed according to stern-volmer equation and double-reciprocal equation, and the binding constant and the thermodynamic parameters were obtained.
Assuntos
Dipiridamol/química , Soroalbumina Bovina/química , Animais , Bovinos , Transferência de Energia , Ligação Proteica , Espectrometria de Fluorescência , Termodinâmica , Vasodilatadores/químicaRESUMO
By using a LKB2277 BioActivity Monitor (heat conduction microcalorimeter), stopped-flow method, the thermogenetic curves of Rhizopus nigricans growth at 25 degrees C inhibited by four kinds of heavy metal ions are determined, parameters such as growth rate constants k, inhibitory ratio I, half inhibitory concentration IC50 et al. are obtained. The experimental results show that heavy metal ions can inhibit Rhizopus nigricans growth obviously, low concentration of Cu2+ has promoting action. The inhibitory sequence is Cd2+ > Hg2+ > Pb2+ > Cu2+, half inhibitory concentration of them are Cd+ 0.8 micro g x ml(-1), Hg2+ 1.7 micro g x ml(-1), Pb2+ 48.0 micro g x ml(-1), Cu2+ 110 micro g x ml(-1). This microclorimetric bioassay for acute cellular toxicity is based on metabolic heat evolution from cultured cells. The assay is quantitative, inexpensive, and versatile; moreover, toxicological information can be obtained with cell from other species of interest.