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Disturbance observer (DOB) and extended state observer (ESO) are extensively utilized to handle external disturbances and model uncertainties in the control system. Nevertheless, the integration of these two methods to improve disturbance suppression remains an open question. In this research, the disturbance compensation mechanism of DOB is employed to compensate the disturbance estimation error of ESO, thereby achieving an effective integration of DOB and ESO. Additionally, a generalized ESO (GESO) is proposed to replace ESO. A robust internal mode control (RIMC) scheme is then developed by incorporating GESO into a two-degree-of-freedom internal mode control (TDF-IMC) framework. Moreover, the equivalence of RIMC and classical TDF-IMC is given by a rigorous derivation under the frequency domain description. Finally, the RIMC is applied to the control of a two-inertia system to verify its superiority in terms of robustness, disturbance rejection, and resonance suppression.
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The increasing risk posed by space debris highlights the need for accurate localization techniques. Spaceborne single photon Lidar (SSPL) offers a promising solution, overcoming the limitations of traditional ground-based systems by providing expansive coverage and superior maneuverability without being hindered by weather, time, or geographic constraints. This study introduces a novel approach leveraging non-parametric Bayesian inference and the Dirichlet process mixture model (DPMM) to accurately determine the distance of space debris in low Earth orbit (LEO), where debris exhibits nonlinear, high dynamic motion characteristics. By integrating extended Kalman filtering (EKF) for range gating, our method captures the temporal distribution of reflected photons, employing Markov chain Monte Carlo (MCMC) for iterative solutions. Experimental outcomes demonstrate our method's superior accuracy over conventional statistical techniques, establishing a clear correlation between radial absolute velocity and ranging error, thus significantly enhancing monostatic space debris localization.
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Current low-light enhancement algorithms fail to suppress noise when enhancing brightness, and may introduces structural distortion and color distortion caused by halos or artifacts. This paper proposes a content-illumination coupling guided low-light image enhancement network (CICGNet), it develops a truss topology based on Retinex as backbone to decompose low-light image component in an end-to-end way. The preservation of content features and the enhancement of illumination features are carried out along with depth and width direction of the truss topology. Each submodule uses the same resolution input and output to avoid the introduction of noise. Illumination component prevents misestimation of global and local illumination by using pre- and post-activation features at different depth levels, this way could avoid possible halos and artifacts. The network progressively enhances the illumination component and maintains the content component stage-by-stage. The proposed algorithm demonstrates better performance compared with advanced attention-based low-light enhancement algorithms and state-of-the-art image restoration algorithms. We also perform extensive ablation studies and demonstrate the impact of low-light enhancement algorithm on the downstream task of computer vision. Code is available at: https://github.com/Ruini94/CICGNet .
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PURPOSE: Osthole possesses anti-tumor activities. However, whether osthole can have a radiosensitization effect on hepatic cancer remains unclear. Here, an HCC-LM3 cells-inoculated subcutaneous transplanted tumor was adopted to explore the effect of osthole. METHODS: The tumor-bearing mice were treated with 100â¯mg/kg osthole for 12 days, 4â¯Gy irradiation twice, or their combination. The tumor volume and weight, lactic acid content, glycolytic enzyme activities, and protein expression of glycogen synthase kinase 3ß (GSK-3ß), pGSK-3ß, mammalian target of rapamycin (mTOR), pmTOR, AMP-activated protein kinase (AMPK), pAMPK, glucose transporter 1/3, and pyruvate kinase M2 were determined. The GSK-3ß-overexpressed HCC-LM3 or SK-Hep1 cell models were also adopted to verify the effects of osthole on expression of these proteins. RESULTS: The tumor volume and weight, lactic acid content, and glycolytic enzyme activities in tumor tissues were lower in the ostholeâ¯+ radiation group than in the radiation group. Moreover, osthole could reverse the radiation-induced increments of pGSK-3ß/GSK-3ß and pmTOR/mTOR protein ratios and the expression of glucose transporter 1/3 and pyruvate kinase M2 proteins in tumor tissues, and increase the protein ratio of pAMPK/AMPK. The effects of osthole on these glycolysis-related proteins were also observed in GSK-3ß-overexpressed HCC-LM3 or SK-Hep1 cell models. CONCLUSION: Osthole has a radiosensitizing effect on subcutaneous transplanted hepatocellular carcinoma, and its mechanism may be related to inhibition of GSK-3ß/AMPK/mTOR pathway-controlled glycolysis.
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The inherent small divergence angle of space optical communication poses significant challenges to establishing communication links. Therefore, laser link acquisition becomes a crucial technology in optical communication, with a primary focus on reducing the acquisition time effectively. Conventional optical communication acquisition techniques fail to address the error effects caused by satellite insertion into the Earth orbit, thus unable to meet the rapid establishment demands of laser links in satellite optical communication networks. In this regard, we propose a novel, to the best of our knowledge, on-orbit calibration method for laser communication terminals to our knowledge. Leveraging stellar observations, this method achieves efficient on-orbit calibration with only a single observation. Theoretical analysis and on-orbit experimental results demonstrate that this approach effectively enhances an open-loop pointing accuracy, offering promising prospects for achieving a rapid establishment of optical communication links in ultra-long-distance optical communication missions.
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Mono-static system benefits from its more flexible field of view and simplified structure, however, the backreflection photons from mono-static system lead to count loss for target detection. Counting loss engender range-blind, impeding the accurate acquisition of target depth. In this paper, count loss is reduced by introducing a polarization-based underwater mono-static single-photon imaging method, and hence reduced blind range. The proposed method exploits the polarization characteristic of light to effectively reduce the count loss of the target, thus improving the target detection efficiency. Experiments demonstrate that the target profile can be visually identified under our method, while the unpolarization system can not. Moreover, the ranging precision of system reaches millimeter-level. Finally, the target profile is reconstructed using non-local pixel correlations algorithm.
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With the development of space laser communication and the planned deployment of satellite Internet constellations, there is a growing demand for microminiature laser communication terminals. To meet the requirements of size, weight and power (SWaP), miniaturized terminals require smaller drive components to complete on-orbit scanning and capture, which must be fast and efficient to enable satellite laser communication networks. These miniaturized laser communication terminals are highly susceptible to the impact of the initial pointing accuracy of the laser beam and microvibrations of the satellite platform. Therefore, this paper proposes a laser scanning-capture model based on a Micro-electromechanical Systems (MEMS) micromirror that can provide a fast, large-scale scanning analysis. A scanning overlap factor is introduced to improve the capture probability under the influence of microvibrations. Finally, experimental analysis was carried out to verify the effectiveness of the proposed model, which can establish a theoretical basis for future ultra-long-distance microspace laser communication.
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The cardiotoxicity of trastuzumab (TRZ) seriously affects the prognosis of breast cancer patients, but the underlying mechanisms remains to be elucidated. This study aimed to investigate the potential molecular mechanisms of TRZ-induced cardiotoxicity based on RNA sequencing (RNA-Seq) and bioinformatics analysis. Kunming mice were exposed to 10 mg/kg TRZ for 6 and 10 days, followed by echocardiography, histopathology and serum biochemical analysis to evaluate the cardiotoxicity model. The results showed no significant changes after 6 days administration of TRZ. After 10 days administration of TRZ, the mice showed cardiac dysfunction, myocardial injury and fibrosis, and the serum levels of LDH, CK, CK-MB and cTnI were increased compared to the control [CON (Day 10)] group, indicating the cardiotoxicity model was successfully established. We compared gene expression levels in mice cardiac tissues by RNA-Seq and screened out 593 differentially expressed genes (DEGs). Results based on Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) network analysis and RT-PCR revealed that the CD74/STAT1 signaling pathway might play an important role in TRZ-induced cardiotoxicity. In the TRZ group, the protein expressions of CD74, p-STAT1 (Tyr) and p-STAT1 (Ser) were increased. The TUNEL staining showed increased apoptosis of cardiomyocytes. In addition, an increased expressions of Bax, Caspase-3, IFN-γ and TNF-α and a decreased expression of Bcl-2 were observed in Western blot results, indicating the apoptosis and inflammation levels were increased. These findings suggested that TRZ may induce cardiotoxicity in mice by activating the CD74/STAT1 signaling pathway, which might be related to the induction of apoptosis and inflammation.
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Cardiotoxicidade , Doxorrubicina , Camundongos , Animais , Trastuzumab/toxicidade , Análise de Sequência de RNA , InflamaçãoRESUMO
Osthole is a natural coumarin substance that has an inhibitory effect on hepatic cancer, but its radiosensitization effect on hepatoma cells has not been reported. This study aimed to investigate the effect of osthole. Human HCC-LM3 and SK-Hep-1 hepatoma cells were used and treated with or without osthole, irradiation, or their combination; the cell survival, migration, colony formation, DNA damage repair, intracellular lactic acid content, and glycolysis-related glycogen synthase kinase-3ß (GSK-3ß), p-GSK-3ß, AMP-activated protein kinase (AMPK), p-AMPK, mammalian target of rapamycin (mTOR), p-mTOR, glucose transporter-1 (GLUT-1), GLUT-3, and pyruvate kinase isozyme type M2 (PKM2) protein expressions were determined. Compared with the irradiation group, the osthole plus irradiation group could further decrease the survival rate, migration, colony formation, and DNA damage repair of both hepatoma cells, indicating a synergistic effect of the combination treatment. Moreover, the combination of osthole and irradiation could decrease the content of intracellular lactic acid, ratios of intracellular p-GSK-3ß/GSK-3ß and p-mTOR/mTOR proteins, and expressions of intracellular GLUT-1/3 and PKM2 proteins, and increase the ratio of intracellular p-AMPK/AMPK proteins. Osthole can increase the radiosensitivity of hepatoma cells, and its radiosensitization mechanisms may be related to glycolytic inhibition by attenuating the GSK-3ß/AMPK/mTOR pathway.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Serina-Treonina Quinases TOR/metabolismo , Cumarínicos/farmacologia , Linhagem Celular Tumoral , Glicólise , Tolerância a Radiação , Ácido Láctico/farmacologiaRESUMO
In recent years, the fine particles suspended in the atmosphere, especially the particle size less than 10 µ m , have caused very adverse effects on the climate environment and human health. However, the current research on the causes of air pollution mainly focuses on human activities and weather conditions. Considering the weak magnetism and chargeability of atmospheric fine particles, this study proposed a new view that space electromagnetic radiation may affect the physical properties of fine particles. We first analyzed the dynamic characteristics of magnetic micro-particle in the electromagnetic environment, and built a simulation model in the COMSOL simulation software. Finally, based on the theoretical analysis and simulation results, we built an experimental verification system to evaluate the effects of electromagnetic radiation on the physical properties of micro-particle, and carried out a 30-day control experiment. The experimental results showed that the physical properties such as particle size distribution, mass concentration, and morphology of suspended fine particles in the atmosphere under electromagnetic radiation are significantly different from those under non-electromagnetic radiation environment. It can be inferred that the aggregation, fusion, and deposition of suspended particles in the atmosphere are closely related to the complex electromagnetic environment in space.
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Osthole is a natural product that has an inhibitory effect on liver cancer, but its effect on the sensitivity of liver cancer to sorafenib is poorly understood. Here, we investigated the effect of osthole and possible sensitization mechanisms. Our results showed that the combination of 2.5 µM sorafenib and 10 µM osthole had significantly synergistic inhibitory effects on proliferation, colony formation, and migration of HCCLM3, sorafenib-resistant HCCLM3 (HCCLM3-SR), and SK-Hep-1 cells. After treatment of HCCLM3 cells-inoculated subcutaneous xenotransplanted tumor mice with 100 mg/kg osthole, 70 mg/kg sorafenib or their combination for 24 day, the tumor volume, tumor weight, and tumor weight coefficient were significantly lower in the osthole + sorafenib group than in the sorafenib group. Compared with the control group, the total cholesterol and low density lipoprotein-cholesterol contents in serum and tumor tissue were significantly decreased in the osthole or osthole + sorafenib groups, the sterol regulatory element binding protein (SREBP)-2c, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and low-density lipoprotein receptor (LDLR) protein expressions in tumor tissue were significantly downregulated as well. In conclusion, osthole can increase the sensitivity of liver cancer to sorafenib, and the mechanism is related to the downregulations of SREBP-2c, HMGCR, and LDLR protein expressions and subsequent inhibition of cholesterol metabolism.
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Neoplasias Hepáticas , Proteína de Ligação a Elemento Regulador de Esterol 2 , Animais , Colesterol/metabolismo , Cumarínicos , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Sorafenibe/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismoRESUMO
We used radioresistant SU3-5R stem cells-inoculated subcutaneous glioma model to investigate the radiosensitization effect of apigenin. After treatment of glioma with apigenin 20 mg/kg for 12 days, irradiation 8 Gray twice or their combination, the tumor volume and weight were decreased, especially in the combination group. Apigenin inhibited the activities of glycolytic enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues. After treatment of SU3-5R cells with apigenin 7.5 µM, the fluorescence intensity of CD133 positive cells was decreased, the percentage of cells with comet tails was increased, and the expressions of lipopolysaccharide-induced NF-κB p65, HIF-1α, GLUT-3 and PKM2 proteins were reduced. These results demonstrate that apigenin can sensitize the radiotherapy of glioma via the attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolytic enzymes and protein expressions.
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Glioma , NF-kappa B , Animais , Apigenina/farmacologia , Apigenina/uso terapêutico , Dano ao DNA , Glioma/tratamento farmacológico , Glioma/radioterapia , Glicólise/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , NF-kappa B/metabolismoRESUMO
Apigenin, a flavonoid isolated from Apium graveolens, is an effective natural active ingredient that inhibits transforming growth factor-ß1 (TGF-ß1)-induced cardiac fibroblasts (CFs) differentiation and collagen synthesis. However, its effects on isoproterenol-induced myocardial fibrosis in mice remain unknown. This study aimed to examine the effect of apigenin in the prevention of myocardial fibrosis. A mouse model of myocardial fibrosis induced by isoproterenol was established, and the mice were given apigenin 75-300 mg/kg orally for 40 days. The results showed that the heart weight coefficient, myocardial hydroxyproline, collagen accumulation, and malondialdehyde levels in the apigenin-treated groups were significantly reduced. In contrast, the activity of myocardial superoxide dismutase and glutathione peroxidase were significantly enhanced. The results of real-time quantitative polymerase chain reaction and western blot assays showed that apigenin could significantly upregulate the expressions of myocardial microRNA-122-5p (miR-122-5p), c-Ski, and Smad7 and downregulate the expressions of myocardial miR-155-5p, α-smooth muscle actin, collagen I/III, NF-κB, TGF-ß1, hypoxia-inducible factor-1α (HIF-1α), Smad2/3, and p-Smad2/3. In vitro, the differentiation and extracellular matrix production, as well as TGF-ß1/Smads axis, were further reduced after treatment of miR-122-5p mimic or miR-155-5p inhibitor-transfected and TGF-ß1-stimulated CFs with apigenin. These results suggested that apigenin increased the expression of miR-122-5p and decreased the expression of miR-155-5p, which subsequently downregulated and upregulated the target genes HIF-1α and c-Ski, respectively. Furthermore, apigenin administration downregulated TGF-ß1-induced Smad2/3 and upregulated Smad7. In addition, it reduced the NF-κB/TGF-ß1 signaling pathway axis by increasing antioxidant ability to exert the antifibrotic effects.
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Apigenina , Cardiomiopatias , MicroRNAs , Estresse Oxidativo , Animais , Apigenina/uso terapêutico , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/tratamento farmacológico , Colágeno/metabolismo , Fibrose , Isoproterenol , Camundongos , MicroRNAs/genética , NF-kappa B/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: Stevioside is a natural diterpenoid compound that possesses anti-inflammatory, immunomodulatory, anti-diabetic, anti-hypertensive, and renal protective effects, but its effect on lipopolysaccharide (LPS)-induced epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells, an important immune pathological mechanism of renal fibrosis, remains unknown. This study employed the renal proximal tubular cells NRK-52E to investigate the effect of stevioside. METHODS: The LPS-stimulated renal NRK-52E cells were treated with 50, 100, or 200 µM stevioside in the presence or absence of peroxisome proliferator-activated receptor γ (PPARγ) antagonist GW9662, the expression levels of intracellular E-cadherin, vimentin, α-smooth muscle actin (α-SMA), PPARγ, nuclear factor kappa B (NF-κB) p65, transforming growth factor-ß1 (TGF-ß1), signal transducer and activator of transcription 3 (STAT3), p-STAT3, Smad2/3, and p-Smad2/3 proteins were detected by Western blot analysis. RESULTS: In LPS-stimulated NRK-52E cells, stevioside treatment could reverse the expressions of EMT-related E-cadherin, vimentin, and α-SMA proteins, increase the expression of PPARγ protein, and decrease the expressions of NF-κB p65, TGF-ß1, p-STAT3, Smad2/3, and p-Smad2/3 proteins, especially in the 200 µM stevioside-treated group. However, these beneficial effects of stevioside were attenuated or canceled by pretreatment with PPARγ antagonist GW9662. CONCLUSIONS: Stevioside can inhibit the LPS-induced EMT via the reductions of NF-κB, TGF-ß1, Smad2/3, p-Smad2/3, and p-STAT3 protein expressions by PPARγ activation in NRK-52E cells, which may provide a pharmacological basis for the potential application of stevioside in the prevention and treatment of renal fibrosis.
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Lipopolissacarídeos , PPAR gama , Linhagem Celular , Diterpenos do Tipo Caurano , Células Epiteliais , Transição Epitelial-Mesenquimal/fisiologia , Fibrose , Glucosídeos , Humanos , Lipopolissacarídeos/toxicidade , PPAR gama/metabolismo , PPAR gama/farmacologia , Fator de Crescimento Transformador beta1RESUMO
Apigenin, a natural flavonoid compound present in a variety of edible plants and health foods, has an anti-tumor effect and inhibits hypoxia inducible factor-lα (HIF-1α) expression in hypertrophic cardiac tissues. However, whether or not apigenin has a radiosensitization effect on glioma stem cells (GSCs) is unknown. Our present study aimed to investigate the effect of apigenin and its possible mechanisms. The human GSCs SU3 and its radioresistance line SU3-5R were treated with apigenin, radiation, or their combination, and the cell proliferation, migration, colony formation, and intracellular lactic acid and glycolytic related protein expressions were determined. Additionally, a cell model with hypoxia-induced HIF-1α expression was used and treated with apigenin. The current results displayed that the combination of apigenin and radiation could synergically reduce the viability, colony formation, and migration of the both GSCs. Moreover, this combination could also decrease the radiation-induced increments of glycolytic production lactic acid in the both GSCs and related protein expressions, including HIF-1α, glucose transporter (GLUT)-1/3, nuclear factor kappa B (NF-κB) p65, and pyruvate kinase isozyme type M2 (PKM2). Further study confirmed that after treatment of hypoxia-cultured SU3 or SU3-5R cells with apigenin, the expression levels of HIF-1α, GLUT-1/3, NF-κB p65, and PKM2 proteins were reduced. These results demonstrated that apigenin could increase the radiosensitivity of GSCs and its radiosensitization mechanisms were attributable to the attenuation of glycolysis, which might result from the inhibition of HIF-1α expression and subsequent reductions of GLUT-1/3, NF-κB, and PKM2 expressions.
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Apigenina/farmacologia , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Glicólise/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Radiossensibilizantes/farmacologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Glioma/metabolismo , Glioma/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da TireoideRESUMO
For highly efficient photocatalytic remediation of organic pollutants, broad-spectrum light response and effective charge separation are two key goals. To achieve these goals, a novel biochar (BC) modified PbMoO4 composite catalyst was successfully synthesized in situ by combining coprecipitation with pyrolysis treatment of poplar sawdust and the technical feasibility of degradation of tetracycline (TC) with compound photocatalyst prepared from recovered agricultural and forestry residues was preliminarily demonstrated. The characterization demonstrated that the presence of BC narrowed the bandgap, enhanced visible light absorption as well as facilitated charge separation. Three composites (with the mass ratio of PbMoO4 to BC = 1:4; 1:1; and 4:1, respectively) displayed higher activity than pure PbMoO4. The results showed that the composite with the PbMoO4 to BC ratio of 1:4 exhibited the best photocatalytic activity, for 150 mg L-1 TC the removal rate was 61.0%, and the rate constant was 8.1 × 10-3 min-1, while the photocatalytic activity of PbMoO4 was 26.0% and 3.9 × 10-3 min-1. The reactions in the presence of radical quenchers indicated that holes (h+) and superoxide radicals (O2-) were the dominant active species for photodegradation. In different water matrices, for 150 mg L-1 TC solution the photocatalytic activity of optimal photocatalyst decreased as follows: ultrapure water > artificial sewage > farm sewage > municipal sewage. Moreover, the catalyst exhibited good stability over five cycles. Therefore, BC doped PbMoO4 provides a useful strategy for improving the photocatalytic ability of PbMoO4-based photocatalysts and offers a promising method for water purification.
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Carvão Vegetal , Tetraciclina , Catálise , LuzRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Apigenin is a natural flavonoid compound present in chamomile (Matricaia chamomilla L.) from the Asteraceae family, which is used in the treatment of cardiovascular diseases by traditional healers, but its effects on differentiation and extracellular matrix (ECM) production of cardiac fibroblasts (CFs) induced by transforming growth factor beta 1 (TGF-ß1) are poorly understood. AIM OF THE STUDY: This study aimed to examine these effects and potential molecular mechanisms and to provide a new application of apigenin in the prevention and treatment of cardiac fibrosis. MATERIALS AND METHODS: The TGF-ß1-stimulated CFs or the combination of TGF-ß1-stimulated and microRNA-155-5p (miR-155-5p) inhibitor- or mimic-transfected CFs were treated with or without apigenin. The expression levels of intracellular related mRNA and proteins were detected by real-time polymerase chain reaction and Western blot methods, respectively. The luciferase reporter gene containing cellular Sloan-Kettering Institute (c-Ski) wild or mutant type 3'-UTR was used and the luciferase activity was examined to verify the direct link of miR-155-5p and c-Ski. RESULTS: After treatment of TGF-ß1-stimulated CFs with 6-24⯵M apigenin, the expression of c-Ski was increased, while levels of miR-155-5p, α-smooth muscle actin, collagen â /â ¢, Smad2/3, and p-Smad2/3 were decreased. After transfection of CFs with the miR-155-5p inhibitor or mimic, the similar or inverse results were respectively observed as well. The combination of TGF-ß1 and miR-155-5p inhibitor or mimic might cause an antagonistical or synergistic effect, respectively, and apigenin addition could enhance the effects of the inhibitor and antagonize the effects of the mimic. Luciferase reporter gene assay demonstrated that c-Ski was a direct target of miR-155-5p. CONCLUSION: These findings suggested that apigenin could inhibit the differentiation and ECM production in TGF-ß1-stimulated CFs, and its mechanisms might partly be attributable to the reduction of miR-155-5p expression and subsequent increment of c-Ski expression, which might result in the inhibition of Smad2/3 and p-Smad2/3 expressions.
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Apigenina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Animais , Apigenina/isolamento & purificação , Células Cultivadas , Proteínas de Ligação a DNA/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Matricaria/química , Camundongos , MicroRNAs/genética , Miocárdio/citologia , Proteínas Proto-Oncogênicas/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
This study aimed to examine the inhibitory effect of stevioside on unilateral ureteral obstruction (UUO)-induced kidney fibrosis. The UUO mice were daily given 50-100 mg/kg stevioside by gavage for 14 days after the operation. The results showed that stevioside decreased the levels of blood urea nitrogen and renal hydroxyproline, severity of kidney fibrosis, and expressions of renal collagen I/III and α-smooth muscle actin proteins. Importantly, stevioside increased the expressions of renal peroxisome proliferator-activated receptor γ (PPARγ) and Smad7 proteins and level of renal glutathione peroxidase, decreased the expressions of renal nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), p-STAT3, transforming growth factor-ß1 (TGF-ß1), Smad2/3, and p-Smad2/3 proteins, suggesting that the antifibrotic mechanisms are related to the activation of PPARγ and subsequent downregulations of NF-κB-mediated STAT3 and TGF-ß1 expressions and inhibition of Smad-mediated signaling pathway. These findings provide an applied perspective of stevioside for kidney fibrosis. PRACTICAL APPLICATIONS: Stevioside is widely used in food products as a sweetener, and it has many beneficial biological effects, including antidiabetes, antihypertension, and renal protective action. Here, we provide a novel potential application of stevioside in the prevention and treatment of kidney fibrosis.
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Obstrução Ureteral , Animais , Diterpenos do Tipo Caurano , Fibrose , Glucosídeos , Rim/patologia , Camundongos , PPAR gama , Obstrução Ureteral/complicações , Obstrução Ureteral/patologiaRESUMO
Herein, an all-solid-state sequential self-organization and self-assembly process is reported for the in situ construction of a color tunable luminous inorganic/polymer hybrid with high direct piezoresponse. The primary inorganic self-organization in solid polymer and the subsequent polymer self-assembly are achieved at high pressure with the first utilization of piezo-copolymer (PVDF-TrFE) as the host matrix of guest carbon quantum dots (CQDs). This process induces the spontaneous formation of a highly ordered, microscale, polygonal, and hierarchically structured CQDs/PVDF-TrFE hybrid with multicolor photoluminescence, consisting of very thermodynamic stable polar crystalline nanowire arrays. The electrical polarization-free CQDs/PVDF-TrFE hybrids can efficiently harvest the environmental available kinetic mechanical energy with a new large-scale group-cooperation mechanism. The open-circuit voltage and short-circuit current outputs reach up to 29.6 V cm-2 and 550 nA cm-2 , respectively. The CQDs/PVDF-TrFE-based hybrid nanogenerator demonstrates drastically improved durable and reliable features during the real-time demonstration of powering commercial light emitting diodes. No attenuation/fluctuation of the electrical signals is observed for ≈10 000 continuous working cycles. This study may offer a new design concept for progressively but spontaneously constructing novel multiple self-adaptive complex inorganic/polymer hybrids that promise applications in the next generation of self-powered autonomous optoelectronic devices.
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Apigenin has a protective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced mouse liver injury through the increments of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and peroxisome proliferator-activated receptor γ (PPARγ) expressions, but its exact mechanisms are still uncertain. This study aimed to further verify its protective effect on hepatocytes and to determine its target of action. The results showed that after treatment of D-GalN/LPS-stimulated hepatocytes with 2.5-20 µM apigenin, the supernatant alanine aminotransferase, aspartate aminotransferasein, tumor necrosis factor-α, and malondialdehyde levels and intracellular nuclear factor-κB protein expression were decreased, while the supernatant superoxide dismutase (SOD) and catalase (CAT) levels, intracellular PPARγ and inhibitor of kappa B-alpha protein expressions, and nucleus Nrf-2 protein expression were increased. After pretreatment with BML-111 or GW9662, the apigenin-induced nucleus Nrf-2 or intracellular PPARγ protein expressions were completely inhibited, respectively, but the both pretreatment differently affected the protective effect of apigenin on hepatocytes. The former completely canceled the protective effect, whereas the latter did not. These findings further demonstrate that apigenin can exert a protective effect on D-GalN/LPS-induced hepatocellular injury via the increment of Nrf-2 nucleus translocation, which may increase the SOD and CAT levels and PPARγ protein expression and subsequently inhibit the inflammatory response.