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1.
Biomater Sci ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842122

RESUMO

Oxidative stress (OS) plays an important role in the emergence and prevention of neurodegenerative diseases, such as Alzheimer's disease (AD). Excess reactive oxygen species (ROS) accumulated in a neuronal cell can lead to OS, producing cell injury and death. Seeking nanoantioxidants against AD-related oxidative stress has attracted a lot of attention, especially those potential antioxidant agents derived from natural polyphenols. However, the transformation of abundant plant polyphenols to antioxidative biomaterials against OS is still challenging. In this work, we report a new method to transform amorphous tannic acid (TA) into tailorable shaped ellagic acid (EA) crystalline particles without using an organic solvent. EA crystalline particles were generated from TA, which underwent a chemical transformation, in situ metal phenolic coordination and acid-induced assembly process, and the size and shape could be controlled by varying the amount of acid. As-prepared EA crystalline particles showed excellent stability in water and lysosomal mimicking fluid and possess unique fluorescence properties and a strong response in mass spectrometry, which is beneficial for their imaging analysis in cells and tissues. More importantly, EA particles have shown significant H2O2-related ROS scavenging ability, a high cellular uptake capacity, an excellent neuroprotective effect in PC12 cells, a high drug loading capacity and BBB permeability to enter the brain. Our study suggested that the EA crystalline particles show great potential for OS-mediated AD treatment.

2.
ACS Appl Bio Mater ; 7(5): 3154-3163, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38695332

RESUMO

ß-Galactosidase (ß-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor ß-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine ß-Gala activity effectively. Via the sensing performance, the catalytic activity of ß-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-ß-d-galactopyranoside (KOßDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing ß-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of ß-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.


Assuntos
Neoplasias da Mama , Quempferóis , Teste de Materiais , Nanopartículas , Silício , beta-Galactosidase , Humanos , beta-Galactosidase/metabolismo , Silício/química , Células MCF-7 , Nanopartículas/química , Quempferóis/química , Quempferóis/farmacologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Tamanho da Partícula , Colorimetria , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Feminino , Estrutura Molecular
4.
Anal Chim Acta ; 1280: 341880, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37858561

RESUMO

ß-Glucosidase (ß-Gluco) is an enzyme that is crucial to numerous diseases, including cancer, and in sector of industries, it is used in the manufacturing of food. Measuring its enzymatic activity is critical for biomedical studies and other activities. Herein, we have developed a novel and precise fluorescent sensing method for measuring ß-Gluco activity based on the production of yellow-green fluorescent quercetin-silicon nanoparticles (Q-SiNPs) produced from quercetin (QN) as a reducing agent and 3-[2-(2-aminoethyl amino) ethylamino] propyl-trimethoxy silane (AEEA) as a silane molecule. ß-Gluco hydrolyzed quercetin-3-O-ß-d-glucopyranoside (QO-ß-DG) to produce QN, which was then used to produce Q-SiNPs. Reaction parameters, including temperature, time, buffer, pH, and probe concentration, were carefully tuned in this study. Subsequently, the fluorescence intensity was performed, showing good linearity (R2 = 0.989), a broad linear dynamic range between 0.5 and 12 U L-1, and a limit of detection (LOD) as low as 0.428 U L-1, which was proven by fluorescence measurements. Most importantly, various parameters were detected and characterized with or without ß-Gluco. The designed probe was successively used to assess ß-Gluco activity in human serum and moldy bread. However, the mathematical findings revealed recoveries for human serum ranging from 99.3 to 101.66% and for moldy bread from 100.11 to 102.5%. Additionally, Q-SiNPs were well suited to being incubated in vitro with L929 and SiHa living cells, and after using an Olympus microscope, imaging showed good fluorescence cell images, and their viability evinced minimal cytotoxicity of 77% for L929 and 88% for SiHa. The developed fluorescence biosensor showed promise for general use in diagnostic tests. Therefore, due to this outstanding sensing modality, we anticipate that this research can provide a novel schematic project for creating simple nanostructures with a suitable plan and a green synthetic option for enzyme activity and cell imaging.


Assuntos
Celulases , Nanopartículas , Humanos , Quercetina , Silício/química , Silanos , Nanopartículas/química , Corantes Fluorescentes/química
5.
Nanoscale ; 15(43): 17464-17472, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37860933

RESUMO

Abnormal expression of acetylcholinesterase (AChE) causes Alzheimer's disease (AD). Inhibiting AChE is a common strategy for reducing the degradation of neurotransmitter acetylcholine, in order to treat early-stage AD. Therefore, it is crucial to screen and explore AChE inhibitors which are safer and cause fewer side effects. Our research is focused on establishing a platform of ruptured organosilica nanocapsules (RONs) immobilized AChE coupled with an MnO2-OPD colorimetric assay, which could monitor AChE activity and screen AChE inhibitors. The fabricated RONs immobilized AChE possessed excellent pH and thermal stability. Huperzine A was introduced into the established platform to evaluate the inhibition kinetics of the immobilized AChE, which promoted its application in the screening of AChE inhibitors. The satisfactory results of enzyme inhibition kinetics proved the feasibility and applicability of the established method. Thus, the proposed platform was applied to screen AChE inhibitors from 14 compounds isolated from Inula macrophylla, and ß-cyclocostunolide (compound 4) demonstrated the best AChE inhibitory activity among these compounds. This work confirms the existence of chemical components that inhibit AChE activity in Inula macrophylla, and provides a new idea for the application of immobilized enzyme-nanozyme in the field of enzyme inhibitor screening.


Assuntos
Doença de Alzheimer , Inula , Nanocápsulas , Acetilcolinesterase/química , Inula/metabolismo , Nanocápsulas/uso terapêutico , Compostos de Manganês , Óxidos , Inibidores da Colinesterase/farmacologia , Doença de Alzheimer/tratamento farmacológico
6.
J Agric Food Chem ; 71(40): 14814-14824, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37782472

RESUMO

Residues of endocrine disrupting steroid hormones in food might cause various diseases like cardiovascular diseases and breast and prostate cancers. Monitoring steroid hormone levels plays a vital role in ensuring food safety and exploring the pathogenic mechanism of steroid hormone-related diseases. Based on the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction, a novel chemoselective probe, Azo-N3, which contains a reactive site N3, an imidazolium salt-based MS tag, and an azobenzene-based photoswitchable handle, was designed and synthesized to label ethynyl-bearing steroid hormones. The probe Azo-N3 was applied for the highly selective and sensitive detection of four ethynyl-bearing steroid hormones in food samples (milk, egg, and pork) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The ionization efficiency of the labeled analytes could be increased by 6-105-fold, and such a labeled method exhibited satisfactory detection limits (0.04-0.2 µg/L), recovery (80.6-122.4%), and precision (RSDs% lower than 6.9%). Interestingly, the efficient immobilization of the probe Azo-N3 onto α-cyclodextrin (α-CD)-modified magnetic particles to construct a solid supported chemoselective probe Fe3O4-CD-Azo-N3 and UV light-controlled release of the labeled analytes from a magnetic support can be achieved by taking advantage of the photoswitched host-guest inclusion between the azobenzene unit and α-CD. The potential applications of Fe3O4-CD-Azo-N3 for labeling, capturing, and the photocontrolled release of the labeled steroid hormones were fully investigated by mass spectrometry imaging analysis. This work not only provides a sensitive and accurate method to detect steroid hormones in food but also opens a new avenue in designing solid supported chemoselective probes.


Assuntos
Hormônios , Espectrometria de Massas em Tandem , Humanos , Masculino , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Esteroides/química , Cromatografia Líquida de Alta Pressão/métodos
8.
ACS Appl Mater Interfaces ; 14(28): 31702-31714, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35796026

RESUMO

Hydroxyapatite (HA) bioceramic coating has been extensively applied for the modification of metallic implants to improve their biocompatibility and service life after implantation. Unfortunately, HA coating often suffers from high friction, severe wear, and bacterial invasion, which restrict its application in artificial joints. According to a bioinspired soft/hard combination strategy, a novel HA composite coating that is infiltrated with a vancomycin-loaded graphene oxide (GO) hybrid supramolecular hydrogel is developed via vacuum infiltration and a subsequent host-guest interaction-induced self-assembly process. The holes of textured HA ceramic coating act just like a "magic pocket", offering a stable container to form and store GO hybrid hydrogels and even to recycle wear debris as well. The drug-loaded hybrid hydrogels stored in textured HA coating possess a unique shear force and/or frictional heat triggered gel-sol transition and sustained drug release behavior, acting like the extrusion of synovial fluid during articular cartilage movement, leading to a remarkable self-lubrication, anti-wear performance, and promising antibacterial property against Staphylococcus aureus. The friction coefficient and wear rate of composite coating reduced by nearly five times and three orders of magnitude compared with textured HA coating, respectively, which benefited from the synergistic lubricate effect of cyclodextrin-based pseudopolyrotaxane supramolecular hydrogel and GO lubricants.


Assuntos
Grafite , Hidrogéis , Antibacterianos/farmacologia , Durapatita/farmacologia , Grafite/farmacologia , Hidrogéis/farmacologia
9.
Nanoscale ; 14(27): 9806-9817, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35770915

RESUMO

Bacterial infections can cause serious complications in cancer treatment and have been proven to weaken therapeutic benefits. Recently, antibacterial nanomaterials that serve as carriers for anticancer drug delivery have been attracting extensive interest due to their combined antimicrobial and anticancer activities. In this study, antibacterial metal-phenolic nanosheets (Cu-TA) were successfully prepared via the self-assembly of the metal-phenolic coordination complexes formed between copper ions and tannic acid, and the structure, morphology, and formation mechanism of Cu-TA nanosheets were explored. The antibacterial activity of Cu-TA nanosheets against both Gram-positive and Gram-negative bacteria was detected using the minimum inhibitory concentration (MIC), zone of inhibition and plate counting methods. The MIC values of both bacterial strains were about 0.4 mg mL-1, and the killing rates of Cu-TA samples were close to 100% at the concentration of 2 and 0.2 mg mL-1 after 12-hour incubation. Epirubicin hydrochloride (EPI) molecules were successfully loaded on the porous Cu-TA nanosheets mainly through the formation of the Cu-EPI chelate complex and strong electrostatic interactions. The Cu-EPI complex and Cu-TA nanosheets could be disassembled under acidic conditions or in the presence of high levels of glutathione (GSH) after uptake by cancer cells, which triggered the unique pH and GSH-responsive controlled release behaviors of EPI and copper ions. The MTT assay results revealed that the presence of bacteria in Hep G2 cells can greatly impair the cell death rate induced by free EPI, but the resultant EPI-loaded Cu-TA nanosheets can significantly enhance cell death both in the presence and absence of bacteria.


Assuntos
Antibacterianos , Cobre , Antibacterianos/química , Bactérias , Cobre/química , Preparações de Ação Retardada/farmacologia , Epirubicina/química , Epirubicina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Metais/química
10.
Mikrochim Acta ; 189(6): 222, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579762

RESUMO

Branched titanium dioxide nanorods (B-TiO2 NRs) grown on fluorine-doped tin oxide glass (FTO) were developed, which can be used as a solid-phase extractant for preconcentration and determination of trace Pb(II) combined with inductively coupled plasma optical emission spectrometry (ICP-OES). The B-TiO2 NR-based glass substrate displayed excellent adsorptive selectivity and capacity for Pb(II); the maximum adsorption capacity was found to be 168.4 mg⋅g-1 PB(II) at pH = 5.0. It proved that the primary extraction mechanism was attributed to soft acid/soft base interactions to form complexes for chemisorption. Investigating the adsorption kinetics and isotherms indicated that the pseudo-second-order and Langmuir models can better describe Pb(II) adsorption on the B-TiO2 NRs. The proposed method presented good linearity from 0.01 to 5 mg⋅L-1 with a correlation coefficient (R2) of 0.9989 and a low limit of detection (LOD) of 2.2 µg⋅L-1 for Pb(II) under optimal conditions. The method was successfully applied to Pb(II) determination in foodstuffs with desirable recoveries from 93.18 to 108.1% and good precision with an RSD of less than 12.2%. This work provides a new strategy for selective extraction and determination of Pb(II) in complicated matrix samples.


Assuntos
Nanotubos , Extração em Fase Sólida , Chumbo , Extração em Fase Sólida/métodos , Titânio/química
11.
J Chromatogr A ; 1665: 462824, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35051752

RESUMO

Acetylcholinesterase (AChE) is generally considered to be a valuable therapeutic target for Alzheimer's disease (AD). To rapidly screen novel AChE inhibitors from Traditional Chinese medicines (TCMs), polydopamine (PDA) coated hollow urchin-shaped manganese dioxide microspheres (h-MnO2@PDA) were fabricated in this work. AChE was immobilized onto the surface of h-MnO2@PDA for the first time, and the prepared h-MnO2@PDA immobilized AChE coupled with capillary electrophoresis (CE) was applied to AChE inhibitor screening. The enzyme catalytic activity and kinetic performances of the immobilized AChE were determined by measuring the peak areas of 5-thio-2-nitrobenzoic acid (TNB), which was produced by the reaction of thiocholine (TCh) with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB). Inhibition kinetics for the immobilized AChE was performed by employing huperzine A as model inhibitor, and its inhibition constant and IC50 were determined. The constructed AChE immobilized h-MnO2@PDA presented outstanding pH, thermal and storage stability. Ultimately, the constructed strategy was applied to screen AChE inhibitors from 7 TCMs and Schisandrae Chinensis Fructus was screened out for its superior AChE inhibitory activity. Therefore, our work not only established a platform for efficiently screening novel AChE inhibitors from TCMs, but also provided inspiration for further exploration of Schisandrae Chinensis Fructus as a potential drug for AD.


Assuntos
Acetilcolinesterase , Inibidores da Colinesterase/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Enzimas Imobilizadas , Compostos de Manganês , Microesferas , Óxidos
12.
J Mater Chem B ; 9(48): 9852-9862, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34704586

RESUMO

Inspired by the structure and dynamic weeping lubricating mechanism of articular cartilage, a novel composite coating composed of a textured Y2O3-stabilized ZrO2 (YSZ) ceramics reservoir and silver nanoparticles (AgNPs) hybrid supramolecular hydrogel was developed on the basis of a soft/hard combination strategy. The precursor solution including the poly(ethylene glycol) (PEG)-modified AgNPs and α-cyclodextrins (α-CDs) could be infiltrated deep into (50-60 µm) the pores of a textured YSZ ceramics substrate by a vacuum infiltration method, in situ forming a supramolecular hydrogel within the pores through host-guest inclusion between α-CDs and PEG chains distributed onto the surface of AgNPs. The AgNPs hybrid hydrogel showed thixotropic and thermoresponsive gel-sol transition behavior, low cytotoxicity, and excellent drug-loading capacity, as well as significant antibacterial properties. The textured YSZ ceramics not only provided a hard supporting skeleton and stable reservoir to protect the supramolecular hydrogel from destruction under load-bearing or shear condition, but also allowed retaining the stimuli-responsive gel-sol transition property and drug-release capability of the infiltrated hydrogel, endowing the composite coating with excellent antibacterial properties, and self-lubrication and wear-resistance performance. The composite coating in this work brings a new insight into the design of antibacterial and self-lubricating ceramic coatings for artificial joint applications.


Assuntos
Antibacterianos/farmacologia , Cerâmica/farmacologia , Escherichia coli/efeitos dos fármacos , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Cerâmica/síntese química , Cerâmica/química , Hidrogéis/síntese química , Hidrogéis/química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Teste de Materiais , Testes de Sensibilidade Microbiana , Tamanho da Partícula
13.
J Chromatogr A ; 1651: 462302, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34119720

RESUMO

Phospholipids are one of the main nutrients in rice, which have a positive effect on cancer, coronary heart disease and inflammation. However, phospholipids will become small molecular volatile substances during the aging process of rice, resulting in change the flavor of rice. Therefore, mapping the concentration and the spatial distribution of phospholipids in rice are of tremendous significance in its function research. In this work, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) imaging method for the spatial distribution analysis of phospholipids in rice. A total of 12 phospholipid compounds were found in the range of m/z 500-1000 through a series of conditions optimization. According to the results, lysophosphatidylcholine (LPC) species spread throughout the rice tissue sections and phosphatidylcholine (PC) species distributed in the bran and embryo (particularly in the scutellum). We also compared the signal intensities of phospholipids in different parts of white rice and brown rice by region of interest (ROI) analysis, which showed the relative content of PC species was higher in the embryo and gradually decreased until disappeared with the increase of processing degree during the processing of brown rice to white rice. The PC species on the surface of rice could be used as an important indicator to identify the processing degree of rice. Our work not only establish a MALDI-TOF-MS imaging method for spatial distribution analysis of rice, but also provide the necessary reference for ensuring food security, improving the eating quality of rice and the health benefits of consumers.


Assuntos
Análise de Alimentos/métodos , Oryza/química , Fosfolipídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Lasers , Lisofosfatidilcolinas/análise , Fosfatidilcolinas/análise
14.
J Mater Chem B ; 9(14): 3200-3209, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33885624

RESUMO

Making full use of the undeveloped bioactive natural product derivatives by selectively delivering them to target sites can effectively increase their druggability and reduce the wastage of resources. Azo-based prodrugs are widely regarded as an effective targeted delivery means for colon-related disease treatment. Herein, we report a new-type of azo-based nanoprodrug obtained from bioactive natural products, in which the readily available podophyllotoxin natural products are connected with methoxy polyethylene glycol (mPEG) via a multifunctional azobenzene group. The amphiphilic prodrug can form nanosized micelles in water and will be highly selectively activated by azoreductases, leading to the in situ generation of anticancer podophyllotoxin derivatives (AdP) in the colon after the cleavage of the azo bond. To satisfy the demand of drug carriers for cancer combination therapy in clinics, α-CD is further introduced into this nanoprodrug micelle system to form a supramolecular hydrogel via a cascade self-assembly strategy. Using imaging mass spectrometry (IMS), the colon-specific drug release ability of the hydrogel after oral administration is demonstrated at the molecular level. Finally, the nanoprodrug hydrogel is further used as a carrier to load a hydrophilic anti-cancer drug 5-FU during the hierarchical self-assembly process and to co-deliver AdP and 5-FU for the drug combination. The combination use of AdP and 5-FU provides enhanced cytotoxicity which indicates a significant synergistic interaction. This work offers a new way to enhance the therapeutic effect of nanoprodrugs via drug combination, and provides a new strategy for reusing bioactive natural products and their derivatives.


Assuntos
Antineoplásicos/farmacologia , Hidrogéis/química , Nanopartículas/química , Podofilotoxina/farmacologia , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Hidrogéis/síntese química , Micelas , Estrutura Molecular , Tamanho da Partícula , Podofilotoxina/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Células Vero
15.
Talanta ; 225: 122086, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592797

RESUMO

A novel magnetic C3N5 framework material (Fe3O4/C3N5) was developed as a high selectivity extractant for La(III) determination in food samples. The Fe3O4/C3N5 material was synthesized by thermal deammoniation method and has larger surface area (100.3 m2 g-1) and more effective adsorption sites compared with that of individual C3N5 material (19.4 m2 g-1). It was proved that Fe3O4/C3N5 material displayed excellent selectivity and adsorption capacity for La(III). In addition, adsorption isotherm and kinetic data indicated that La(III) adsorption based on Fe3O4/C3N5 material is a monolayer adsorption which is compatible with Langmuir model and follows a pseudo-second-order kinetic equation. By using Fe3O4/C3N5 material as extractant, an analytical method was established with low limits of detection (3σ, n = 6) of 10.4 µg L-1, reasonable recoveries ranged from 86% to 106% and good precision with the RSD less than 10.7%. The analytical method was further applied to the determination of trace La(III) in food sample. It evinced that the concentration of La(III) in sea fish is 13.2 µg kg-1 and the content of 138La is 0.138 µg kg-1, which is 1.03% of total La(III).

16.
Macromol Biosci ; 21(1): e2000299, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33043625

RESUMO

Injectable hydrogels for nonsteroidal anti-inflammatory drugs' (NSAIDs) delivery to minimize the side effects of NSAIDs and achieve long-term sustained release at the targeted site of synovial joint are attractive for osteoarthritis therapy, but how to improve its mechanical strength remains a challenge. In this work, a kind of 1D natural clay mineral material, attapulgite (ATP), is introduced to a classical cyclodextrin pseudopolyrotaxane (PPR) system to form a reinforced supramolecular hydrogel for sustained release of diclofenac sodium (DS) due to its rigid, rod-like morphology, and unique structure, which has great potential in tissue regeneration, repair, and engineering. Investigation on the interior morphology and rheological property of the obtained hydrogel points out that the ATP distributed in PPR hydrogel plays a role similar to the "reinforcement in concrete" and exhibits a positive effect on improving the mechanical properties of PPR hydrogel by regulating their interior morphology from a randomly distributed style to the well-ordered porous frame structure. The hybrid hydrogels demonstrate good shear-thinning and thixotropic properties, excellent biocompability, and sustained release behavior both in vitro and in vivo. Furthermore, preliminary in vivo treatment in an acute inflammatory rat model reveals that the ATP hybrid hydrogels present sustained anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Regeneração Óssea/efeitos dos fármacos , Hidrogéis/farmacologia , Compostos de Magnésio/farmacologia , Osteoartrite/tratamento farmacológico , Compostos de Silício/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Ciclodextrinas/farmacologia , Diclofenaco/farmacologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos/efeitos dos fármacos , Humanos , Hidrogéis/química , Injeções Intra-Articulares , Osteoartrite/patologia , Poloxâmero/farmacologia , Polietilenoglicóis/farmacologia , Ratos , Rotaxanos/farmacologia
17.
Front Genet ; 12: 827444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35111208

RESUMO

Gastric cancer is a common cancer afflicting people worldwide. Although incremental progress has been achieved in gastric cancer research, the molecular mechanisms underlying remain unclear. In this study, we conducted bioinformatics methods to identify prognostic marker genes associated with gastric cancer progression. Three hundred and twenty-seven overlapping DEGs were identified from three GEO microarray datasets. Functional enrichment analysis revealed that these DEGs are involved in extracellular matrix organization, tissue development, extracellular matrix-receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, focal adhesion, and protein digestion and absorption. A protein-protein interaction network (PPI) was constructed for the DEGs in which 25 hub genes were obtained. Furthermore, the turquoise module was identified to be significantly positively coexpressed with macrophage M2 infiltration by weighted gene coexpression network analysis (WGCNA). Hub genes of COL1A1, COL4A1, COL12A1, and PDGFRB were overlapped in both PPI hub gene list and the turquoise module with significant association with the prognosis in gastric cancer. Moreover, functional analysis demonstrated that these hub genes play pivotal roles in cancer cell proliferation and invasion. The investigation of the gene markers can help deepen our understanding of the molecular mechanisms of gastric cancer. In addition, these genes may serve as potential prognostic biomarkers for gastric cancer diagnosis.

18.
Analyst ; 145(22): 7397-7405, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32935670

RESUMO

In this work, acid and matrix-tolerant multifunctionalized gold nanoparticles (AuNPs) with an integrated chiral selector towards tyrosine (Tyr) and polyethylenglycol (PEG) chains were developed for visual chiral discrimination of Tyr in biological samples under acid conditions. In brief, AuNPs multifunctionalized with N-acetyl-l-cysteine (NALC) and PEG (PEG/NALC-AuNPs) were prepared via a simple strategy. In the presence of l-Tyr, the color of PEG/NALC-AuNP solution changed from red to gray, while no obvious color change was observed with the introduction of d-Tyr, which indicated that the introduction of PEG onto the surface of AuNPs has no effect on the chiral recognition between l-Tyr and NALC. A computer-aided molecular model was used to clarify the chiral recognition mechanism between NALC and Tyr enantiomers and to further guide the optimization of sensitivity. The resultant PEG/NALC-AuNP sensor presented a significantly improved stability under acid and alkali conditions compared with conventional NALC-AuNPs, resulting in a wider dynamic range (500 nM-100 µM) and a 50 times reduced detection limit by simply adjusting the pH of the sensor system under acid conditions (pH 2-2.5). More importantly, the PEG/NALC-AuNPs can realize the visual chiral discrimination of Tyr enantiomers in biological samples due to their significantly improved long-term stability and reduced interaction towards non-target species.


Assuntos
Ouro , Nanopartículas Metálicas , Acetilcisteína , Colorimetria , Polietilenoglicóis , Tirosina
19.
Anal Chem ; 92(13): 9039-9047, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32501673

RESUMO

We report the development of an azoreductase-responsive prodrug AP-N═N-Cy in which the precursor compound AP, a readily available podophyllotoxin derivative, is linked with a NIR fluorophore (Cy) via a multifunctional azobenzene group. This type of azo-based prodrug can serve as not only an azoreductase-responsive NIR probe to real-time tracking of the drug delivery process but also a delivery platform for an anticancer compound (AdP). We have shown that cleavage of the multifunctional azobenzene group in AP-N═N-Cy only occurred in the presence of azoreductase, which specifically secretes in the colon, resulting in direct release of AdP through an in situ modification of a phenylamino group on the precursor AP. Moreover, introduction of the azobenzene group endows the prodrug with an unique fluorescence "off-on" property and served as a switch to "turn on" the fluorescence of Cy as consequence of a self-elimination reaction with breakage of an azo bond. Such a prodrug can be administered orally and exhibit high stability and low toxicity before arriving at the colon. In view of the synchronism of drug release and the fluorescence turn-on process, the fluorescence imaging method was utilized to precisely trace drug delivery in vitro, ex vivo, and in vivo. Distinguishingly, the biodistribution of AdP and Cy in various tissues was further precisely mapped at the molecular level using imaging mass spectrometry. To the best of our knowledge, this is the first time that the in vivo real-time precise tracking of the colon-specific drug release and biodistribution was reported via a multimodal imaging method.


Assuntos
Compostos Azo/química , Colo/diagnóstico por imagem , Portadores de Fármacos/química , NADH NADPH Oxirredutases/metabolismo , Imagem Óptica/métodos , Pró-Fármacos/química , Animais , Compostos Azo/metabolismo , Carbocianinas/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Corantes Fluorescentes/química , Humanos , Cinética , Espectrometria de Massas , Camundongos , Microscopia Confocal , Nitrorredutases , Pró-Fármacos/metabolismo , Distribuição Tecidual
20.
Talanta ; 215: 120916, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32312459

RESUMO

Element doping is considered as an effective strategy to adjust the interlayer distance of graphitic carbon nitride (g-C3N4) and the element doped g-C3N4 can be applied in metal extraction. Here, a series of potassium(I) doped graphitic carbon nitride (g-C3N4-K) materials with modulated interlayer distance ranging from 3.257 Å to 3.198 Å were successfully synthesized by calcining the different doped ratios mixture of melamine and KOH. Interestingly, g-C3N4-K (Q(melamine):Q(KOH) = 7:1) composite achieves the optimal properties and displays excellent extraction capacity and selectivity for barium [Ba(II)]. It is attributed to the correlation between K dopants and interlayer distance of g-C3N4-K, which highlighted the effect of doped K on the decreasing interlayer. Furthermore, an original extraction method coupled with ICP-OES based on g-C3N4-K was established for Ba(II) and successfully applied in detection of trace Ba(II) in water sample from Yellow River and sample of sea fish.

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