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1.
Langmuir ; 40(21): 11087-11097, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38718184

RESUMO

Photocatalytic technology is an attractive option for environmental remediation because of its green and sustainable nature. However, the inefficient utilization of solar energy and powder morphology currently impede its practical application. Here, we designed a floatable photocatalyst by anchoring 0D Cu2(OH)PO4 (CHP) nanoparticles on 2D graphene to construct 0D/2D CHP/reduced graphene oxide (rGO) aerogels. The CHP/rGO aerogels have interconnected mesopores that provide a large surface area, promoting particle dispersion and increasing the number of active sites. Moreover, the optical response of the CHP/rGO aerogel has been significantly expanded to cover the full spectrum of the solar light. Notably, the 20%CHP/rGO aerogel displayed a high degradation rate (k = 0.178 min-1) taking methylene blue (MB) as a model pollutant under light irradiation (λ > 420 nm). The enhanced photocatalytic activity is ascribed to the rapid electron transfer in the CHP/rGO heterostructures, as supported by the DFT theoretical calculations. Our research highlights the utilization of full spectrum responsive photocatalysts for the elimination of organic pollutants from wastewater under solar light irradiation, as well as the potential for catalyst recovery using floatable aerogels to meet industrial requirements.

2.
Angew Chem Int Ed Engl ; 59(23): 8991-8997, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32078223

RESUMO

In hunting for safe and cost-effective materials for post-Li-ion energy storage, the design and synthesis of high-performance solid electrolytes (SEs) for all-solid-state batteries are bottlenecks. Many issues associated with chemical stability during processing and storage and use of the SEs in ambient conditions need to be addressed. Now, the effect of water as well as oxyhdryl group (. OH) on NaBi3 O4 Cl2 are investigated by evaluating ionic conductivity. The presence of water and . OH results in an increase in ionic conductivity of NaBi3 O4 Cl2 owing to diffusion of H2 O into NaBi3 O4 Cl2 , partially forming binding . OH through oxygen vacancy repairing. Ab initio calculations reveal that the electrons significantly accumulate around . OH and induce a more negative charge center, which can promote Na+ hopping. This finding is fundamental for understanding the essential role of H2 O in halide-based SEs and provides possible roles in designing water-insensitive SEs through control of defects.

3.
Mol Pharm ; 15(12): 5637-5645, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30422663

RESUMO

Dabrafenib is a novel targeted antimelanoma drug. The present work explored the binding mechanism of dabrafenib-human serum albumin (HSA) and the effect on the esterase-like activity and antioxidant activity of HSA by using 19F NMR, spectroscopy methods, and molecular dynamics simulation. The results of 19F NMR, fluorescence, and time-resolved fluorescence spectroscopy revealed that dabrafenib spontaneously binds to the subdomain IIIA of the HSA by hydrophobic action and forms a static complex. The binding affects the esterase-like activity of HSA but not its antioxidant activity. According to the results of molecular dynamics simulation, dabrafenib interacts with Arg410 and Tyr411, which are the key residue associated with the esterase-like activity of HSA. Meanwhile, dabrafenib does not interact with Cys34, the key residue associated with the antioxidant activity of HSA. The results of circular dichroism spectroscopy and molecular dynamics simulation show that the conformation of HSA is not affected by the binding of dabrafenib. This study can provide useful information for understanding the pharmacokinetic properties of dabrafenib.


Assuntos
Antineoplásicos/farmacocinética , Esterases/metabolismo , Imidazóis/farmacocinética , Oximas/farmacocinética , Albumina Sérica Humana/metabolismo , Antineoplásicos/química , Sítios de Ligação , Dicroísmo Circular , Cisteína/metabolismo , Esterases/química , Interações Hidrofóbicas e Hidrofílicas , Imidazóis/química , Simulação de Dinâmica Molecular , Oximas/química , Ligação Proteica , Albumina Sérica Humana/química , Espectrometria de Fluorescência
4.
Ann Allergy Asthma Immunol ; 118(6): 704-709, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28583263

RESUMO

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. OBJECTIVE: To investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. METHODS: Serum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. RESULTS: Serum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. CONCLUSION: The present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.


Assuntos
Antígenos CD/sangue , Caderinas/sangue , Urticária/sangue , Adolescente , Adulto , Antígenos CD/imunologia , Caderinas/imunologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Criança , Doença Crônica , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Histamina/farmacologia , Humanos , Masculino , Fosforilação/efeitos dos fármacos , Índice de Gravidade de Doença , Adulto Jovem
5.
J Obstet Gynaecol Res ; 43(9): 1428-1440, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28613016

RESUMO

AIM: The association between parity and rheumatoid arthritis (RA) risk has been investigated, but results are controversial. Thus, our aim was to systematically analyze the effect of number of parity on the risk of RA in women. METHODS: Relevant published studies were identified using PubMed and embase databases through 1 April 2016. We pooled the relative risks (RR) and 95% confidence intervals (CI) using random-effects models. RESULTS: In all, 12 studies with a total of 2 497 580 participants and 11 521 RA cases were included. A borderline significant inverse association was observed when we compared parity with nulliparity for RA, with summarized RR = 0.90 (95%CI: 0.79-1.02; I2  = 58.5%, Pheterogeneity  = 0.010). In dose-response analysis, we observed a significant nonlinear (Pnonlinearity  = 0.000) relation between parity number and the risk of RA. Compared with null parity, the pooled RR of RA were 0.89 (95%CI: 0.86-0.93), 0.84 (95%CI: 0.79-0.89), 0.85 (95%CI: 0.79-0.90), 0.88 (95%CI: 0.81-0.95), 0.90 (95%CI: 0.83-0.97), 0.92 (95%CI: 0.84-1.02), and 0.94 (95%CI: 0.83-1.07) for 1, 2, 3, 4, 5, 6, and 7 live births, respectively. Subgroup and sensitivity analyses showed similar associations. No publication bias was found. CONCLUSION: The findings from the current meta-analysis indicate that parity was related to decreased risk of RA. The greatest risk reduction appeared when the parity number reached two. Further studies are warranted to confirm our findings.


Assuntos
Artrite Reumatoide/epidemiologia , Estudos Observacionais como Assunto , Paridade , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
6.
Luminescence ; 32(7): 1123-1130, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28378400

RESUMO

The interaction of synthetic azo dye Acid Red 14 with pepsin was studied by fluorescence spectroscopy, UV-vis spectroscopy, circular dichroism and molecular docking. Results from the fluorescence spectroscopy show that Acid Red 14 has a strong capability to quench the intrinsic fluorescence of pepsin with static quenching. Binding constant, number of the binding sites and thermodynamic parameters were measured at different temperatures. The result indicates that Acid Red 14 interact with pepsin spontaneously by hydrogen bonding and van der Waals interactions. Three-dimensional fluorescence spectra and circular dichroism spectra reveal that Acid Red 14 could slightly change the structure of pepsin. The hydrogen bond is formed between Acid Red 14 and Tyr-189 and Thr-218 residues of pepsin. Furthermore, the binding between Acid Red 14 and pepsin inhibits pepsin activity. The study can provide a way to analyze the biological safety of Acid Red 14 on digestive proteases or other proteins.


Assuntos
Compostos Azo/química , Pepsina A/química , Compostos Azo/metabolismo , Sítios de Ligação , Dicroísmo Circular , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Pepsina A/metabolismo , Espectrometria de Fluorescência , Termodinâmica
7.
Phys Chem Chem Phys ; 18(48): 33171-33179, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27892578

RESUMO

Structural modification, especially the stabilization of metastable phases at room temperature, has emerged as an effective strategy to understand their stabilization mechanism and improve their functional properties. In this work, a facile solvothermal approach is developed to synthesize metastable sodium niobate (NaNbO3) crystals with the cubic symmetry. XRD, Raman and TEM results all confirmed the selective synthesis of cubic and orthorhombic NaNbO3via adjustment of the reaction medium. The fact that traditional hydrothermal synthesis often yields orthorhombic NaNbO3 inspires us to elucidate the formation mechanism of cubic NaNbO3 with respect to the solvent effect. With the increasing post-calcination temperature, the as-synthesized cubic NaNbO3 gradually transforms into the orthorhombic structure, which is understood to be a recrystallization behavior, as evidenced by the XRD and TEM results. The organic molecules retained in the NaNbO3 nanocrystals, as suggested by UV-vis, FT-IR and TGA-MS results, have contributed to the stabilization of the metastable structure, demonstrated by the different temperature-induced phase transition behaviors in air and argon atmospheres, where the phase transition from cubic to orthorhombic would take place at a relatively higher temperature in argon. This work provides an alternative approach to synthesize cubic NaNbO3 nanocrystals, and the understanding of the stabilization mechanism could pave a new pathway for fabricating metastable materials.

9.
RSC Adv ; 13(12): 8281-8290, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36926008

RESUMO

The food sector uses methyl yellow (MY) extensively as a colorant. The primary transporter in vivo that influences MY absorption, metabolism, distribution, and excretion is human serum albumin (HSA). Exploring the binding process and looking at how HSA and MY work physiologically at the molecular level is therefore very important. Experiments using steady-state fluorescence and fluorescence lifetimes proved that HSA and MY's quenching mechanisms were static. The HSA-MY complex's binding constant was estimated using thermodynamic parameters to be around 104 M-1. The hydrophobic forces were a major factor in the binding process, as evidenced by the negative ΔG, positive ΔH, and ΔS, which suggested that this contact was spontaneous. Site tests showed that MY linked to HSA's site I. Circular dichroism and three-dimensional fluorescence analysis revealed that the 1.33% α-helix content dropped and the amino acid microenvironment altered. While HSA's protein surface hydrophobicity decreased when engaging MY, the binding of MY to HSA reduced in the presence of urea. The stability of the system was assessed using molecular modeling. Additionally, HSA's esterase-like activity decreased when MY was present, and Ibf/Phz affected the inhibition mechanism of MY on HSA. These findings offer a distinctive perspective for comprehending the structure and functioning of HSA and evaluating the safety of MY.

10.
Int J Biol Macromol ; 235: 123868, 2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-36870639

RESUMO

Metal-organic frameworks (MOFs) have a potential application in blood purification, but their microcrystalline nature has hampered their industrial application. Here, novel MOFs-polymer beads based on UiO, sodium alginate, polyacrylic acid, and poly (ethylene imine) were prepared and applied as a whole blood hemoadsorbent for the first time. The amidation among polymers immobilized UiO66-NH2 into the network of the optimal product (SAP-3), and the NH2 of UiO66-NH2 significantly increased the removal rate (70 % within 5 min) of SAP-3 on bilirubin. The adsorption of SAP-3 on bilirubin mainly obeyed the pseudo-second-order kinetic, Langmuir isotherm and Thomas models with a maximum adsorption capacity (qm) of 63.97 mg·g-1. Experimental and density functional theory simulation results show that bilirubin was mainly adsorbed by UiO66-NH2via electrostatic force, hydrogen bonding, and π-π interactions. Notably, the adsorption in vivo show that the total bilirubin removal rate in the whole blood of the rabbit model was up to 42 % after 1 h of adsorption. Given its excellent stability, cytotoxicity, and hemocompatibility, SAP-3 has a great potential in hemoperfusion therapy. This study proposes an effective strategy for settling the powder property of MOFs and could provide experimental and theoretical references for application of MOFs in blood purification.


Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Animais , Coelhos , Bilirrubina/química , Heparina , Polímeros/química , Adsorção , Etilenos , Poluentes Químicos da Água/química
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 270: 120868, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35032760

RESUMO

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10^4 L mol-1. Thermodynamic parameters exhibited that the binding was a spontaneous process with hydrophobic forces as the main driving force. Fluorescence competition experiments revealed that DBN bound to site I of HSA IIA subdomain. According to the results of synchronous fluorescence, 3D fluorescence, FT-IR spectroscopy, circular dichroism (CD) spectroscopy, and molecular dynamics (MD) simulation, DBN did not affect the basic skeleton structure of HSA but changed the microenvironment around the amino acid residues. Computer simulations positively corroborated the experimental results. Moreover, DBN decreased the surface hydrophobicity and weakened the esterase-like activity of HSA, leading to the impaired function of the latter. This work provides important information for studying the interaction between DBN as a nicotine substitute and biological macromolecules and contributes to the further development and application of DBN.


Assuntos
Simulação de Dinâmica Molecular , Albumina Sérica Humana , Sítios de Ligação , Dicroísmo Circular , Humanos , Hidroxibenzoatos , Simulação de Acoplamento Molecular , Nicotina , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
12.
J Hazard Mater ; 435: 129042, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35650723

RESUMO

The biocompatibility of metal-organic frameworks (MOFs) is necessary to humans but is far from being sufficiently addressed. This study focused on the effects of microsize on the biocompatibility of MOFs by selecting UiO67 with micron and submicron size as the MOFs models. Under the dose metric of surface area, the binding constant between UiO67 and human serum albumin (HSA) gradually increased with increased UiO67 size. Submicron UiO67 induced stronger conformational transformation and more greatly affected the protein surface hydrophobicity than micron UiO67. Micron UiO67 also inhibited the esterase-like activity of HSA through competitive inhibition mechanism, whereas submicron UiO67 inhibited it through noncompetitive inhibition mechanism. The size of UiO67 had little effect on hemocompatibility. A smaller size of UiO67, corresponded with a higher IC50 value for 293 T and LO2 cells, and the adsorption of HSA can effectively improve cytotoxicity. In vivo toxicity evaluations revealed that all UiO67 did not cause obvious distortion of organs, and they were metabolized primarily in the kidney. These results provided useful information about the toxicity of MOFs and experimental references for the development of MOFs-based engineering materials.


Assuntos
Estruturas Metalorgânicas , Adsorção , Humanos , Estruturas Metalorgânicas/química , Albumina Sérica Humana
13.
ACS Appl Mater Interfaces ; 13(29): 34320-34331, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34275274

RESUMO

Dendrite growth under large current density is the key intrinsic issue impeding a wider application of Li metal anodes. Previous studies mainly focused on avoiding dendrite growth by building an additional interface layer or surface modification. However, the mechanism and factors affecting dendrite growth for Li metal anodes are still unclear. Herein, we analyze the causes for dendrite growth, which leads us to suggest three-dimensional (3D) metal anodes as a promising approach to overcome the dendrite issues. A 3D composite Li anode was prepared from renewable carbonized wood doped with Sn to demonstrate its superior electrochemical performance compared with Li foils. The anode was cycled at various current densities from 0.1 to 10 mA cm-2 for five cycles at each current density, displaying low overpotential compared with conventional Li foils. Long galvanostatic cycling at 1 mA cm-2 for 1000 h and at 2 mA cm-2 for 500 h was achieved without dendrite growth. Further analysis reveals that the 3D structure facilitates surface diffusion by increasing the surface area from 5.23 × 10-3 m2 g-1 (Li foil) to 2.64 m2 g-1 and by creating nanoscale separation walls. The tin alloying effectively prevents non-uniform lithium plating by creating abundant nucleation centers. Additionally, suitable alloying elements for a wider range of 3D Li anodes have been identified from density functional theory calculations.

14.
ACS Appl Mater Interfaces ; 13(39): 46588-46597, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34554746

RESUMO

The surface feature of solid electrolytes fundamentally governs their own physical properties and significantly affects the interaction with the electrode materials. The evaluation of interfacial contact between the electrolyte and the metallic anode is largely relied on the macroscopic contact angle measurement, which is influenced by the intrinsic wettability and the microstructure of the electrolyte. In this work, the surface chemistry of the solid electrolyte is first regulated via facile thermal treatments. Then, scanning probe microscopy (SPM)-based techniques are comprehensively adopted to study the interaction between the electrolyte and metallic anode at the nanoscale. By manipulating the overpotential applied on the SPM tip, the mobile sodium ions at the subsurface of the solid electrolyte can be extracted toward the surface, and the eventual topography of the products is deliberately correlated with the sodium wettability. In this context, the impact of surface treatment on the sodium wettability of the surface layer is systematically evaluated based on the topographic evolution at the nanoscale. Furthermore, the local electrochemical reaction dynamics is revealed by correlating the surface ionic activity and current-voltage (I-V) curves. This work presents a new methodology to effectively evaluate the sodium wettability of the solid electrolyte, and these findings can provide meaningful implications to the surface engineering of ceramic electrolytes for high-performance solid-state batteries.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 258: 119828, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930850

RESUMO

Ligand-receptor molecular recognitionis the basis of biological process. The Saturation Transfer Difference-NMR (STD-NMR) technique has been recently used to gain qualitative and quantitative information about physiological interactions at atomic-resolution. The molecular recognition patterns between Vitamin B12 (VB12) and human serum albumin (HSA) were investigated by STD-NMR supplemented by other spectroscopies and molecular docking. STD-NMR delivered a complete picture that the substituent groups on the tetrapyrrole ring of VB12 interacted with site III of HSA through binding epitope mapping and competitive probe experiments. STD-NMR and fluorescence results proved the moderate binding capability of VB12 and clarified a static, spontaneous, and temperature-sensitive binding mechanism. 3D-fluorencence, FT-IR and circular dichroism spectra showed a compact protein structure by interacting with VB12. Size distribution and surface hydrophobicity showed the surface properties changes of HSA caused by the binding of VB12. Computer simulation confirmed the recognition mode in theory and was compared with experiments. This work is beneficial for understanding the safety and biological action of VB12, and will attract researchers interested in NMR technology.


Assuntos
Albumina Sérica Humana , Vitamina B 12 , Sítios de Ligação , Dicroísmo Circular , Simulação por Computador , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
16.
J Mater Chem B ; 9(28): 5628-5635, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34109969

RESUMO

Hemoperfusion has become the third-generation treatment strategy for patients suffering from hyperbilirubinemia, but adsorbents used for bilirubin removal mostly face intractable problems, such as unsatisfactory adsorption performance and poor hemocompatibility. Metal-organic frameworks (MOFs) are promising adsorbents for hemoperfusion due to their high specific surface areas and easily modified organic ligands. However, their microporous properties and separation have hampered their application. Here, a novel hierarchical core-shell nanoplatform (named Double-PEG) with tailored binding sites and pore sizes based on Fe3O4@C and Uio66-NH2 was constructed. Notably, Double-PEG showed excellent bilirubin uptake of up to 1738.30 mg g-1 and maintained excellent bilirubin removal efficiency in simulated biological solutions. A study on the adsorption mechanism showed that the adsorption of Double-PEG towards bilirubin tended to be chemical adsorption and in accordance with the Langmuir model. Besides, the good separability, recyclability, cytotoxicity and hemocompatibility of Double-PEG show great potential in hemoperfusion therapy. The finding of this study may provide a novel insight into the application of MOF materials in the field of hemoperfusion.


Assuntos
Bilirrubina/isolamento & purificação , Materiais Biocompatíveis/química , Carbono/química , Óxido Ferroso-Férrico/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Adsorção , Bilirrubina/química , Materiais Biocompatíveis/síntese química , Linhagem Celular , Humanos , Cinética , Estruturas Metalorgânicas/síntese química , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Purificação da Água
17.
Allergy Asthma Clin Immunol ; 17(1): 38, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865428

RESUMO

BACKGROUND: IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1. METHODS: The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC-1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot. RESULTS: We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells. CONCLUSIONS: This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119040, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33068900

RESUMO

The interaction between a DPP-4 inhibitor, alogliptin benzoate (AB), and human serum albumin (HSA) was systematically investigated via spectroscopy, microcalorimetry and molecular simulations. Steady-state fluorescence and time-resolved fluorescence spectrometry illustrated that the fluorescence quenching type of AB to HSA was static and caused by the formation of ground state AB-HSA complex. Isothermal titration calorimetry (ITC) combined with fluorescence spectra revealed that the affinity of AB to the subdomain IIA of HSA was moderate with a binding constant in the order of 104. Molecular docking analysis and thermodynamic parameters demonstrated that this combination was maintained by hydrogen bonding along with van der Waals force and hydrophobic force. Circular dichroism and three-dimensional (3D) fluorescence showed that AB increased the hydrophobicity of Trp residue and the α-helix content of HSA by 1.99%. Microdifferential scanning calorimetry revealed that the addition of AB enhanced the thermal stability of HSA. The action forces, binding stability, binding sites, and protein structure of the AB-HSA system were evaluated via molecular dynamics analysis in the simulated environment. On the basis of molecular docking, MD simulation constructed a more reliable 3D model of the AB-HSA complex in terms of spatial structure.


Assuntos
Simulação de Dinâmica Molecular , Albumina Sérica Humana , Benzoatos , Sítios de Ligação , Calorimetria , Dicroísmo Circular , Humanos , Simulação de Acoplamento Molecular , Piperidinas , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Termodinâmica , Uracila/análogos & derivados
19.
Colloids Surf B Biointerfaces ; 201: 111644, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33639512

RESUMO

The clinical efficacy of lenvatinib (LFT) is limited by its poor aqueous solubility and low bioavailability. In this work, LFT-loaded soy phospholipid and sodium glycocholate mixed micelles (LFT-MMs) were prepared through classical co-precipitation. And it was served as an oral administration to address these shortcomings. The preparation conditions were optimized by single-factor experiments. The mass ratio of PC, SGC and LFT, and the species of dispersing media were proved to be decisive factors in controlling the properties of LFT-MMs. The optimal LFT-MMs presented prominent enhancement (500-fold) in LFT solubility, high encapsulation efficiency (87.6 %) as well as suitable stability (>1 month at 4 °C). The biocompatibility of LFT-MMs was estimated by in vitro serum stability measurement and hemolysis test. It showed that serum proteins hardly adhered to the surface of LFT-MMs, and insignificant hemolytic rate (<0.5 %) was observed at the micelles concentration below 1 mg/mL. Cytotoxicity test (MTT assay) was carried out to judge the in vitro antitumor activity. LFT-MMs showed an enhanced inhibitory activity against two main kinds of differentiated thyroid cancer cells over LFT and LFT Mesylate. To estimate the in vivo oral bioavailability of LFT-MMs, SD rats were used as animal model. Notably, the relative bioavailability of LFT-MMs compared with the original form of LFT was 176.7 %. These superior characteristics indicated that the mixed micelles are promising water-soluble formulations suitable for LFT oral delivery.


Assuntos
Micelas , Fosfolipídeos , Administração Oral , Animais , Disponibilidade Biológica , Portadores de Fármacos , Tamanho da Partícula , Compostos de Fenilureia , Quinolinas , Ratos , Ratos Sprague-Dawley , Solubilidade
20.
Int J Biol Macromol ; 184: 101-108, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119545

RESUMO

Lentinan is a natural ß-glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug-drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib-lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib-lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug-drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.


Assuntos
Antineoplásicos/administração & dosagem , Lentinano/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Composição de Medicamentos , Células HCT116 , Células HEK293 , Humanos , Lentinano/química , Lentinano/farmacocinética , Simulação de Dinâmica Molecular , Nanopartículas , Tamanho da Partícula , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacocinética , Piridinas/química , Piridinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Solubilidade , Suspensões
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