Thyroid cancer (TC), the most prevalent endocrine malignancy, has been subjected to various treatment methods. However, the efficacy of asiaticoside (AC) for treating TC remains uncertain.
To explore ...the impact of AC on TC and determine its potential mechanisms of action.
In vitro and in vivo cell line study.
We evaluated the effects of AC on human TC cell lines, namely TPC-1 and FTC-133. Both in vitro and in vivo experimental validations were conducted.
AC significantly diminished the viability and proliferation of TC cells based on the CCK-8 assay and Edu staining findings. Migration and invasion assays revealed that AC effectively curtailed the migration and invasiveness of TC cells. The tube formation assay demonstrated that AC substantially impeded TC cell-induced angiogenesis. Western blot assay revealed that AC significantly reduced the expression levels of TRAF6, HIF-1α, and VEGFA, indicating that AC could potentially exert its anticancer effect by inhibiting the TRAF6/HIF1α pathway. Our in vivo experiments, which involved administering AC to BALB/c nude mice injected with TPC-1 cells, demonstrated significant inhibition of tumor growth and reduction in the expression of Ki-67, TRAF6, HIF-1α, and VEGFA.
Our study highlights the significant inhibitory effect of AC on TC, offering fresh insights and potential drug candidates for TC treatment.
Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is suggested as the consequence of emphysematous destruction of vascular bed and hypoxia of pulmonary microenvironment, ...mechanisms underpinning its pathogenesis however remain elusive. The dysregulated expression of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases and superoxide generation by pulmonary vasculatures have significant implications in the hypoxia-induced PH.
In this study, the involvement of NADPH oxidase subunit 4 (NOX4) in pulmonary arteriolar remodeling of PH in COPD was investigated by ascertaining the morphological alteration of pulmonary arteries and pulmonary blood flow using cardiac magnetic resonance imaging (cMRI), and the expression and correlation of NOX4 with pulmonary vascular remodeling and pulmonary functions in COPD lungs.
Results demonstrated that an augmented expression of NOX4 was correlated with the increased volume of pulmonary vascular wall in COPD lung. While the volume of distal pulmonary arteries was inversely correlated with pulmonary functions, despite it was positively associated with the main pulmonary artery distensibility, right ventricular myocardial mass end-systolic and right ventricular myocardial mass end-diastolic in COPD. In addition, an increased malondialdehyde and a decreased superoxide dismutase were observed in sera of COPD patients. Mechanistically, the abundance of NOX4 and production of reactive oxygen species (ROS) in pulmonary artery smooth muscle cells could be dynamically induced by transforming growth factor-beta (TGF-β), which in turn led pulmonary arteriolar remodeling in COPD lungs.
These results suggest that the NOX4-derived ROS production may play a key role in the development of PH in COPD by promoting distal pulmonary vascular remodeling.
In this work, a polyethyleneimine-grafted graphene oxide (PEI-GO) hybrid material was prepared as an effective filler to improve the anticorrosion performance of waterborne epoxy coating. The ...successful covalent reaction between PEI and GO was confirmed by FTIR, Raman, XPS, XRD and TGA measurement. The epoxy coating filled with modified and unmodified graphene oxide was characterized by SEM and Raman spectroscopy. The results showed that PEI-GO was uniformly dispersed in the epoxy matrix. It was found that the PEI-GO hybrid materials displayed considerable superiorities in improving corrosion resistance of epoxy coating by EIS and SVET. Besides, the optimal content (0.25 wt%) of PEI-GO was obtained through experimental results. Moreover, the desirable anticorrosive property of PEI-GO/EP composite coating is proposed to be mainly attributed to the role of PEI, which fully stimulated the barrier properties of graphene oxide by improving its dispersion in the epoxy coating and also enhanced the crosslink density of epoxy resin by increasing the surface activity of the graphene oxide to the epoxy groups.
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•Polyethylenimine (PEI) was grafted on graphene oxide (GO) surface.•The PEI-GO hybrid improved the compatibility between GO and epoxy resin (EP).•The PEI-GO/EP composite coating had longer service life and better anti-corrosion property.•The presence of PEI-GO hybrid increased the density of epoxy coating and suppressed the corrosion of metal substrate.
Cutaneous injury triggers a cascade of signaling events essential for wound re-epithelialization. CD9, a cell-surface protein, has been implicated in a number of cellular processes by coupling to ...intracellular signaling; however, its exact role in wound healing remains unidentified. We reported that CD9 was downregulated in migrating epidermis, and reelevated to basal level when re-epithelialization was completed. Although low level of CD9 appears to be required for normal wound healing, a significant healing delay was found in CD9-null mice, with wounds gaping wider on day 5 and day 7 post wounding. Further analysis showed that re-epithelialization was adversely affected in CD9-null mice, due to impaired migration of epidermis. Notably, CD9 deficiency caused a persistent enhancement of C-JUN NH2 terminal kinase (JNK) signaling primarily in migrating epidermis with abnormal elevation of matrix metalloproteinase (MMP)-9 detected in CD9-null wounds, leading to excessive degradation of type IV collagen, and thus a defective basement membrane at the wound site. JNK suppression reduced MMP-9 production and therefore ameliorated the healing delay with the appearance of significantly elongated migrating epidermis in CD9-null mice. Our study demonstrated the importance of CD9 in wound re-epithelialization, linking this molecule directly to basement membrane formation and epidermal migration through participating in the regulation of the JNK/MMP-9 pathway.
OBJECTIVE: To investigate the effects and underlying mechanism of controlled ovarian hyperstimulation (COH)-induced supraphysiologic concentration of E₂ on the endometrium and outcome of embryo ...implantation. DESIGN: Prospective experimental study. SETTING: University-based laboratory. ANIMAL(S): Imprinting control region female mice, 8–10 weeks old with regular estrous cycles. INTERVENTION(S): Intraperitoneal injection of 10 IU of pregnant mare serum gonadotropin (PMSG) at noon followed by an additional injection of 10 IU hCG 48 hours later. MAIN OUTCOME MEASURE(S): Uteri were collected from either superovulated or control mice (natural cycle) the morning after hCG administration on day 4 to evaluate and count blastocysts. A mouse blastocyst-endometrium coculture model was used to evaluate blastocyst adhesion to control or COH-treated endometrium. The cystic fibrosis transmembrane conductance regulator (CFTR) expression was determined by immunofluorescence, Western blot, and apoptosis determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay in both natural cycle and COH cycle endometrium. Primary culture of mouse endometrial epithelial cells was established to further determine the effects of various concentrations of E₂ on apoptosis. RESULT(S): We demonstrated that COH had adverse effects on blastocyst adhesion. In addition, COH endometrium exhibited an aberrant up-regulation of CFTR expression and a higher apoptotic rate compared with normal endometrium during the implantation period. Administration of exogenous supraphysiologic concentration of E₂ to primary mouse endometrial epithelial cells mimicked the COH-induced up-regulation of CFTR and apoptosis observed in vivo. Furthermore, inhibition of CFTR activity abrogated E₂-induced apoptosis. CONCLUSION(S): The COH-induced supraphysiologic concentration of E₂ aberrantly up-regulates CFTR, which leads to increased apoptosis in endometrial epithelial cells, resulting in impaired embryo implantation.
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•Adsorption of Mg2+ and K+ on the kaolinite (001) surface was investigated by DFT.•Preferred adsorption cation and type were solved based on binding energy.•Mulliken charge and PDOS ...based bonding mechanism are obtained.•A verification experiment was performed to compare adsorption capacity.
Microscopic adsorption mechanism of Mg2+ and K+ on kaolinite (001) surface in aqueous system was investigated by density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulations. A verification experiment has also been done to compare the adsorption capacity of kaolinite to the two ions. The structure for both hydrated complexes and mono-/bi-dentate adsorption complexes of Mg2+ and K+ in aqueous environment was examined, with radial distribution function and binding energies calculated. Mg(H2O)62+ and K(H2O)6+ are the dominant complexes of hydrated Mg2+ and K+, respectively. Bidentate complexes of Mg2+ and monodentate complexes of K+ are their respective dominant complexes, and the binding energies of all the adsorption complexes of Mg2+ are higher than those of K+. Partial density of states projections combining with Mulliken bond charge and populations show the strong ionic characters and weak bonding and anti-bonding states filling of Mg − Os and K − Os in the adsorption complexes. The adsorption experiment verified that Mg2+ is easier to adsorb on kaolinite surface than K+.
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•Cu2O particles with similar size and controllable morphologies were fabricated.•The relationship between morphology of Cu2O particles and their antibacterial properties was build ...up.•The cubooctahedron-Cu2O hybrid coating exhibited the best antibacterial capacity.•Copper ion and reactive oxygen species are key factors to the antibacterial capacity of Cu2O particles.
Biofouling, a global issue, exerts an adverse impact on ocean shipping, deep-sea exploration, aquaculture and other industries. The addition of Cu2O particles to coatings is the most popular and effective method used for biofouling resistance in the ocean circumstance. Herein, Cu2O particles with three kinds of morphologies, including cube, sphere and cubooctahedron, were fabricated by liquid phase reducing method. Particle size, crystallinity, component, activity in aqueous solution, antibacterial property and copper ion leaching rate were systematically investigated. XRD and XPS jointly reflected that as-prepared Cu2O particles were highly pure and impurity was absent. Among three kinds of Cu2O particles, cubooctahedron Cu2O was the most active, possessed the highest ion leaching rate and exhibited the best antibacterial property. It could be deduced that morphology of Cu2O particles affected its activity in aqueous solution, then impacted release rate and ultimately influenced antibacterial capacity. Morphology and component of bacteria, before and after being exposed to as-synthesized Cu2O-acrylic hybrid coatings were also studied and results proved that copper ion was prone to do a damage to the cell membrane of E.coli rather than B. subtilis because of the difference between cell walls.
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•GO with different aspect ratios were prepared and the uniform GO/epoxy composite coatings were fabricated.•Anti-corrosion performance of composite coatings containing GO sheets with ...different aspect ratio were investigated.•Anti-corrosion mechanism of different GO/epoxy composite coatings were studied.•The aspect ratio of GO sheets was a significant factor for enhancing corrosion resistance of GO/epoxy coatings.
Graphene oxide (GO) has a wide application prospect in the field of metal protection due to its good dispersion, chemical activity and physical barrier property. Herein, graphene oxide sheets with different aspect ratio were first prepared by simply controlling the procedure of chemical exfoliation and then used to fabricate GO/epoxy composite coatings. The morphology and structural features of as-prepared GO sheets were characterized by Raman spectroscopy, X-ray diffraction and atomic force microscopy. The dispersion and anticorrosive performances of GO with different aspect ratios incorporated in epoxy-based waterborne composite coatings were investigated by Raman spectroscopic mapping, electrochemical measurements and scanning vibrating electrode technique. The results demonstrated that the different types of GO showed homogeneous dispersion in epoxy resin and GO with higher aspect ratio exhibited larger corrosion protection potential. Furthermore, the anti-corrosion mechanisms for composite coatings enhanced via GO with different aspect ratio were tentatively proposed, which indicating that the GO sheets with higher aspect ratio provided a more tortuous permeation path for corroding medium and thus displayed better corrosion resistance.
Background: Thyroid cancer (TC), the most prevalent endocrine malignancy, has been subjected to various treatment methods. However, the efficacy of asiaticoside (AC) for treating TC remains ...uncertain. Aims: To explore the impact of AC on TC and determine its potential mechanisms of action. Study Design: In vitro and in vivo cell line study. Methods: We evaluated the effects of AC on human TC cell lines, namely TPC-1 and FTC-133. Both in vitro and in vivo experimental validations were conducted. Results: AC significantly diminished the viability and proliferation of TC cells based on the CCK-8 assay and Edu staining findings. Migration and invasion assays revealed that AC effectively curtailed the migration and invasiveness of TC cells. The tube formation assay demonstrated that AC substantially impeded TC cell-induced angiogenesis. Western blot assay revealed that AC significantly reduced the expression levels of TRAF6, HIF-1alpha, and VEGFA, indicating that AC could potentially exert its anticancer effect by inhibiting the TRAF6/HIF1alpha pathway. Our in vivo experiments, which involved administering AC to BALB/c nude mice injected with TPC-1 cells, demonstrated significant inhibition of tumor growth and reduction in the expression of Ki-67, TRAF6, HIF-1alpha, and VEGFA. Conclusion: Our study highlights the significant inhibitory effect of AC on TC, offering fresh insights and potential drug candidates for TC treatment.
MicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we ...investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan-Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.
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