Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
J Ethnopharmacol ; 328: 117976, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38492794

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangshengjing (GHYSJ) is an effective prescription for delaying progression of Alzheimer's disease (AD) based on the ancient Chinese medical classics excavated from Mawangdui Han Tomb. Comprising a combination of eleven traditional Chinese herbs, the precise protective mechanism through which GHYSJ acts on AD progression remains unclear and has significant implications for the development of new drugs to treat AD. AIM OF THE STUDY: To investigate the mechanism of GHYSJ in the treatment of AD through network pharmacology and validate the results through in vitro experiments. MATERIALS AND METHODS: Chemical composition-target-pathway network and protein-protein interaction network were constructed by network pharmacology to predict the potential targets of GHYSJ for the treatment of AD. The interaction relationship between active ingredients and targets was verified by molecular docking and molecular force. Furthermore, the chemical constituents of GHYSJ were analyzed by LC-MS and HPLC, the effects of GHYSJ on animal tissues were analyzed by H&E staining. An Aß-induced SH-SY5Y cellular model was established to validate the core pathways and targets predicted by network pharmacology and molecular docking. RESULTS: The results of the network pharmacology analysis revealed a total of 155 bioactive compounds capable of crossing the blood-brain barrier and interacting with 677 targets, among which 293 targets specifically associated with AD, which mainly participated in and regulated the amyloid aggregation pathway and PI3K/Akt signaling pathway, thereby treating AD. In addition, molecular docking analysis revealed a robust binding affinity between the principal bioactive constituents of GHYSJ and crucial targets implicated in AD. Our findings were further substantiated by in vitro experiments, which demonstrated that Liquiritigenin and Ginsenosides Rh4, crucial constituents of GHYSJ, as well as GHYSJ pharmaceutic serum, exhibited a significant down-regulation of BACE1 expression in Aß-induced damaged SH-SY5Y cells. This study provides valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD and secondary development of GHYSJ prescription. CONCLUSION: Through network pharmacology, molecular docking, LC-MS, and cellular experiments, GHYSJ was initially confirmed to delay the progression of AD by regulating the expression of BACE1 in Amyloid aggregation pathway. Our observations provided valuable data and theoretical underpinning for the potential therapeutic application of GHYSJ in the treatment of AD.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Neuroblastoma , Humanos , Animais , Simulação de Acoplamento Molecular , Secretases da Proteína Precursora do Amiloide , Doença de Alzheimer/tratamento farmacológico , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Ácido Aspártico Endopeptidases , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
2.
Adv Mater ; 35(23): e2302335, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36995655

RESUMO

High-entropy alloys nanoparticles (HEANPs) are receiving extensive attention due to their broad compositional tunability and unlimited potential in bioapplication. However, developing new methods to prepare ultra-small high-entropy alloy nanoparticles (US-HEANPs) faces severe challenges owing to their intrinsic thermodynamic instability. Furthermore, there are few reports on studying the effect of HEANPs in tumor therapy. Herein, the fabricated PtPdRuRhIr US-HEANPs act as bifunctional nanoplatforms for the highly efficient treatment of tumors. The US-HEANPs are engineered by the universal metal-ligand cross-linking strategy. This simple and scalable strategy is based on the aldol condensation of organometallics to form the target US-HEANPs. The synthesized US-HEANPs exhibit excellent peroxidase-like (POD-like) activity and can catalyze the endogenous hydrogen peroxide to produce highly toxic hydroxyl radicals. Furthermore, the US-HEANPs possess a high photothermal conversion effect for converting 808 nm near-infrared light into heat energy. In vivo and in vitro experiments demonstrated that under the synergistic effect of POD-like activity and photothermal action, the US-HEANPs can effectively ablate cancer cells and treat tumors. It is believed that this work not only provides a new perspective for the fabrication of HEANPs, but also opens the high-entropy nanozymes research direction and their biomedical application.


Assuntos
Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Ligas , Entropia , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Microambiente Tumoral
3.
Anal Chem ; 95(14): 6130-6137, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37002208

RESUMO

The localized surface plasmon resonance (LSPR) property, depending on the structure (morphology and assembly) of nanoparticles, is very sensitive to the environmental fluctuation. Retaining the colorimetric effect derived from the LSPR property while introducing new optical properties (such as fluorescence) that provide supplementary information is an effective means to improve the controllability in structures and reproducibility in optical properties. DNA as a green and low-cost etching agent has been demonstrated to effectively control the morphology and optical properties (the blue shift of the LSPR peak) of the plasmonic nanoparticles. Herein, taking silver nanotriangles (AgNTs) as a proof of concept, we report a novel strategy to induce precisely tunable LSPR and fluorescence-composited dual-mode signals by using mono-DNA first as an etching agent for etching the morphology of AgNTs and later as a template for synthesizing fluorescent silver nanoclusters (AgNCs). In addition, common templates for synthesizing AgNCs, such as l-glutathione and bovine serum albumin, were demonstrated to have the capability to serve as etching agents. More importantly, these biomolecules as dual-functional capping agents (etching agents and templates) follow the size-dependent rule: as the size of the thiolated biomolecule increases, the blue shift of the LSPR peak increases; at the same time, the fluorescence intensity increases. The enzyme that can change the molecular weight (size) of the biomolecular substrates (DNA, peptides, and proteins) through an enzymatic cleavage reaction was explored to regulate the LSPR and fluorescent properties of the resulting nanoparticles (by etching of AgNTs and synthesis of AgNCs), achieving excellent performance in detection of cancer-related proteases. This study can be expanded to other biopolymers to impact both fundamental nanoscience and applications and provide powerful new tools for bioanalytical biosensors and nanomedicine.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Prata/química , Reprodutibilidade dos Testes , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , DNA/química , Soroalbumina Bovina
4.
Chem Commun (Camb) ; 59(12): 1617-1620, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36661262

RESUMO

A novel probe was synthesized with a turn-on NIR fluorescent (NIRF)/photoacoustic (PA) response to NADPH, which was successfully applied in both monitoring intracellular NADPH and dual-modal imaging of tumor-bearing mice. It exhibits good potential in studying and understanding the tumor energy metabolism and treatment process related to NADPH.


Assuntos
Neoplasias , Técnicas Fotoacústicas , Camundongos , Animais , Corantes Fluorescentes , NADP , Análise Espectral , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos
5.
Talanta ; 253: 123919, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126523

RESUMO

Nowadays, proteins separation has attracted great attention in proteomics research. Because the proteins separation is helpful for making an early diagnosis of many diseases. Magnetic nanoparticles are an interesting and useful functional material, and have attracted extensive research interest during the past decades. Because of the excellent properties such as easy surface functionalization, tunable biocompatibility, high saturation magnetization etc, magnetic microspheres have been widely used in isolation of proteins/peptides. Notably, with the rapid development of surface decoration strategies, more and more functional magnetic adsorbents have been designed and fabricated to meet the growing demands of biological separation. In this review, we have collected recent information about magnetic adsorbents applications in selective separation of proteins/peptides. Furthermore, we present a comprehensive prospects and challenges in the field of protein separation relying on magnetic nanoparticles.


Assuntos
Peptídeos , Proteômica , Fenômenos Magnéticos
6.
Anal Chem ; 95(2): 581-586, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36583571

RESUMO

Access to both protein and metabolite biomarker information in biospecimens from trace samples remains a significant challenge, and it is necessary to separate proteins and metabolites before analysis. In this work, the Fe3O4@SiO2@Proteins@Metal-polyphenol network (MPN) was successfully constructed and applied to separate metabolites and proteins. Tannic acid (TA) and Cu2+ were involved in the synthesis of MPN because of rapid degradation and maintaining the assay performance of proteins. There are a variety of interactions between TA and proteins, including hydrogen-bonding, hydrophobic, and ionic interactions. Moreover, benefiting from the small molecule permeability and surface adherence of MPN, proteins were encapsulated and immobilized on the surface of substrates with the growth of MPN. At the same time, endogenous metabolites remained dispersed in the supernatant. In the model sample and real biospecimen cases, the protein biomarkers (e.g., carcinoembryonic antigen and alanine aminotransferase) were encapsulated on the surface of Fe3O4@SiO2, which allowed the isolation of proteins from the original matrix, as well as release and analysis in a short time. Meanwhile, the metabolites in the produced supernatant were analyzed by LC-MS/MS. By the self-assembly and disassembly of MPN, the group differences of proteins and metabolites between physiological and pathological biospecimens are correctly characterized without multisampling. Overall, an MPN-mediated separation strategy of biomarkers was proposed, and MPN facilitated a "two birds with one stone" approach, where the proteins were encapsulated and immobilized in the precipitation while endogenous metabolites distributed in the produced supernatant, opening a new chapter in the application of MPNs.


Assuntos
Polifenóis , Dióxido de Silício , Cromatografia Líquida , Espectrometria de Massas em Tandem , Proteínas , Metais , Taninos/química
7.
ChemSusChem ; 15(24): e202201584, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36195829

RESUMO

Small-molecule induction can lead to the oriented migration of metal elements, which affords functional materials with synergistic components. In this study, phosphating nickel foam (NF)-supported octahedral WO3 with phosphine affords P-WO3 /NF electrocatalyst. Ni is found to form Ni-P bonds that migrate from NF to WO3 under the induction of P, resulting in the complex oxides W1.3 Ni0.24 O4 and Ni2 P2 O7 in the particle interior and nickel phosphide on the octahedral grain surface. The catalytic activity of P-WO3 /NF in the urea oxidation reaction (UOR) is improved by synergistic action of the components in the synthesized hybrid particles. A current density of 10 mA cm-2 can be reached at a potential of 1.305 V, the double layer capacitance of the catalyst is significantly increased, and the electron transfer impedance in catalytic UOR is reduced. This work demonstrates that small-molecule induction is suitable for constructing co-catalysts with complex components in a simple protocol, which provides a new route for the design of highly efficient urea oxidation electrocatalysts.


Assuntos
Níquel , Óxidos , Oxirredução , Transporte de Elétrons , Ureia
8.
Int J Mol Sci ; 23(15)2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35955473

RESUMO

The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans and animals, particularly those involved in the maintenance of intestinal homeostasis, immunity, inflammation, and tumorigenesis. The diversity of bile acids is a result of the joint efforts of host and intestinal microflora. There is a bidirectional relationship between the microbial community of the intestinal tract and bile acids in that, while the microbial flora tightly modulates the metabolism and synthesis of bile acids, the bile acid pool and composition affect the diversity and the homeostasis of the intestinal flora. Homeostatic imbalances of bile acid and intestinal flora systems may lead to the development of a variety of diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), and polycystic ovary syndrome (PCOS). The interactions between bile acids and intestinal flora may be (in)directly involved in the pathogenesis of these diseases.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Neoplasias Hepáticas , Animais , Ácidos e Sais Biliares , Humanos
9.
Molecules ; 27(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35744822

RESUMO

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.


Assuntos
Eucommiaceae , Hipertensão , Doenças Neurodegenerativas , China , Suplementos Nutricionais , Eucommiaceae/química , Humanos
10.
Small ; 18(18): e2200439, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35355393

RESUMO

The intercrystalline interfaces have been proven vital in heterostructure catalysts. However, it is still challenging to generate specified heterointerfaces and to make clear the mechanism of a reaction on the interface. Herein, this work proposes a strategy of Fe-catalyzed cascade formation of heterointerfaces for comprehending the hydrogen evolution reaction (HER). In the pure solid-phase reaction system, Fe catalyzes the in situ conversion of MoO2 to MoC and then Mo2 C, and the consecutive formation leaves lavish intercrystalline interfaces of MoO2 -MoC (in Fe-MoO2 /MoC@NC) or MoC-Mo2 C (in Fe-MoC/ß-Mo2 C@NC), which contribute to HER activity. The improved HER activity on the interface leads to further checking of the mechanism with density functional theory calculation. The computation results reveal that the electroreduction (Volmer step) produced H* prefers to be adsorbed on Mo2 C; then two pathways are proposed for the HER on the interface of MoC-Mo2 C, including the single-molecular adsorption pathway (Rideal mechanism) and the bimolecular adsorption pathway (Langmuir-Hinshelwood mechanism). The calculation results further show that the former is favorable, and the reaction on the MoC-Mo2 C heterointerface significantly lowers the energy barriers of the rate-determining steps.


Assuntos
Hidrogênio , Ferro , Catálise , Hidrogênio/química , Molibdênio/química
11.
Anal Chem ; 94(3): 1769-1777, 2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35020347

RESUMO

The concentrations of nitroreductase and H2S have been widely used to predict the invasiveness of tumors. However, the above two substrates always interfere with the measurement of each other as both substrates react with the typical nitroaromatic probe with the same process. Moreover, the above interferences may lead to the misjudgment of the tumor invasiveness. We used a strategy combining kinetical distinguishing and signal amplification to construct a kinetically orthogonal probe labeled KOP. The above strategy expanded the gap between the reactivity of KOP to H2S and nitroreductase with an acceptable reactivity and could determine the concentration of coexisting nitroreductase and H2S on a kinetic curve with a breakpoint. KOP could also indicate the correct invasiveness tendency in the cellular model with a complex H2S generation pathway, while the traditional kinetically nonorthogonal probe could not indicate invasiveness correctly.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Contagem de Células , Corantes Fluorescentes , Humanos , Nitrorredutases/metabolismo
12.
Small ; 18(10): e2105304, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35032093

RESUMO

The assembly of molecules into hierarchical superstructures is ubiquitous in the construction of novel geometrically complex hierarchical superstructures, attracting great attention. Herein, a metal-ligand cross-linking strategy is developed for the fabrication of ferric ion-dopamine coordination hierarchical superstructures. A range of superstructures with highly complex morphologies, such as flower-like, octopus-like, and hedgehog-like superstructures, are synthesized. The mechanism for formation of hierarchical superstructures involves the pre-cross-linking of ferric ion with dopamine molecules, the fabrication of iron-dopamine precursors aggregated into the spherical aggregates, the nanoscale aggregates sintering and ordering themselves upon equilibration, the nanodots polymerizing into nanorods, and finally the nanorods self-assembling into hierarchical superstructures. In-depth research illustrates that as the permittivity (ξ) of the reaction system increases, the resulting hierarchical superstructures tend to converge into spherical shape. As a proof of concept, the 0D nanospheres, 1D nanorods, and 3D hierarchical superstructures are fabricated through adjusting system permittivity. The hierarchical superstructure is utilized as peroxidase-like ligase mimics to enhance the effect of tumor photothermal treatment. Further in vitro and in vivo assays demonstrate that the hierarchical superstructure can effectively ablate tumor cells. This work opens new horizons in hierarchical superstructures with complex architectures, and has great potential in nanozymology, biomedical science, and catalysis.


Assuntos
Nanotubos , Neoplasias , Proteínas Hedgehog , Humanos , Ligases , Nanotubos/química , Neoplasias/terapia , Terapia Fototérmica
13.
ACS Appl Mater Interfaces ; 12(46): 51185-51197, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33146508

RESUMO

Nitric oxide (NO) is known as one of the most important biomarkers of many diseases. However, the development of NO-triggered drug releasing platforms is challenging due to the low concentration and short lifetime of NO in vivo. In this work, a novel nitrite (NO2-)-responsive hydrogel (DHPL-GEL), which can be used for smart drug release depending on the severity of the NO-related disease, is demonstrated. A dihydropyridine cross-linking agent is designed to construct DHPL-GEL to enable the responsive degradation of the hydrogel triggered by NO2-. On-demand release of the drug loaded in DHPL-GEL was observed under the stimulation of various concentrations of NO2- at the physiological level both in vitro and in vivo. In the inflammatory arthritis rat model, the DHPL-GEL drug delivery system showed a better therapeutic effect and less side effects than the traditional therapy and nonresponsive hydrogel drug delivery system, demonstrating the promising application of the NO2--responsive hydrogel for the treatment of NO-related diseases.


Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Hidrogéis/química , Óxido Nítrico/metabolismo , Nitritos/química , Resinas Acrílicas/química , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Liberação Controlada de Fármacos , Módulo de Elasticidade , Fluoresceína-5-Isotiocianato/química , Fluoresceína-5-Isotiocianato/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metotrexato/química , Metotrexato/metabolismo , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Camundongos , Células RAW 264.7 , Ratos
14.
Carbohydr Polym ; 236: 116094, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172896

RESUMO

Different size and morphology monodispersed chitosan (CS) microspheres loaded with the anticancer drug of 5-fluorouracil (5-Fu) were prepared by the microfluidic method assisted by a crosslinking unit with crosslinkers of tripolyphosphate (TPP) and glutaraldehyde (GTA). The sizes, morphologies, drug loading, encapsulation efficiency, drug release and cytotoxicity of 5-Fu loaded CS microspheres were characterized and determined. Results indicated that the CS microspheres were uniform in size distributions. They possessed excellent encapsulation efficiency and drug loading. The TPP-crosslinked CS microspheres had rough surfaces and exhibited faster drug release, whereas the CS microspheres crosslinked with GTA had smooth surfaces and showed slower drug release. Furthermore, 5-Fu-loaded CS microspheres exhibited sustained drug release which well fitted the first-order kinetics model and were pH-responsive in that the drug cumulative release was greater at acidic environments than at neutral conditions. Finally, 5-Fu loaded CS microspheres provided sufficient cytotoxicity and were satisfactory in the cancer cell inhibition.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Quitosana/química , Portadores de Fármacos/química , Fluoruracila/farmacologia , Microesferas , Antimetabólitos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Liberação Controlada de Fármacos , Fluoruracila/química , Glutaral/química , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Microfluídica/métodos , Polifosfatos/química
15.
ACS Appl Mater Interfaces ; 12(5): 5500-5510, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31939286

RESUMO

Fabrication of functional electrochemical biosensor is a hot topic; however, precise and sensitive cancer detection in early clinical diagnosis is still a great challenge. Continuous efforts have been devoted to explore functional materials for this issue. In this work, we developed a dual binding sites and dual signal-amplifying electrochemical aptasensor of self-polymerized dopamine-decorated Au and coordinated with Fe-MOF (Au@PDA@Fe-MOF) for the detection of carcinoembryonic antigen (CEA). Remarkably, Au@PDA@Fe-MOF features high sensitivity, multiple active sites, good biocompatibility, and excellent selectivity, which is attributed to abundant -COOH in porous Fe-MOF and unsaturated Fe3+ sites on the surface of Fe-MOF as the active binding sites grafting more NH2-functionalized CEA-specific aptamer and redox PDA and Fe-MOF accelerating the movement of electrons for dual signal amplifying. Meanwhile, the electrochemical aptasensor shows favorable repeatability with 1.82% relative standard deviation (RSD) under five independent aptasensors and strong stability with only 3.3% degradation after 12 days of storage. In addition, the aptasensor has wide CEA detection range from 1 fg mL-1 to 1 µg mL-1 with a low detection limit of 0.33 fg mL-1 (S/N = 3). Furthermore, the aptasensor is feasible for accurate and quantitative detection of CEA in serum samples with RSD below 2.32%. The satisfying results demonstrate promising applications of the CEA aptasensor in practical sample analysis and lay an important foundation for other biomarker detection in early clinical diagnosis.


Assuntos
Aptâmeros de Nucleotídeos/química , Antígeno Carcinoembrionário/sangue , Dopamina/química , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química , Sítios de Ligação , Técnicas Biossensoriais/métodos , Ouro/química , Humanos , Ferro/química , Limite de Detecção , Estruturas Metalorgânicas/química , Polímeros/química
16.
Front Physiol ; 10: 494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105592

RESUMO

Tangshen formula (TSF), a formula of Chinese herbal medicine, improves lipid metabolism in humans and animals with diabetic kidney disease. However, the effect and mechanism of TSF on nonalcoholic fatty liver disease (NAFLD) remain unclear. The activation of autophagy appears to be a potential mechanism for improving NAFLD. In the present study, we examined the therapeutic effect of TSF on hepatic steatosis and sought to explore whether its effect is related to activating autophagy. Here, we showed that TSF treatment significantly attenuated hepatic steatosis in both high-fat diet (HFD) and methionine choline-deficient diet (MCDD)-fed mice. Meanwhile, TSF reduced lipid accumulation in palmitate (PA)-stimulated HepG2 cells and primary mouse hepatocytes. Furthermore, TSF increased Sirtuin 1 (SIRT1) expression and promoted autophagy activation in vivo. TSF also improved PA-induced suppression of both SIRT1 expression and SIRT1-dependent autophagy, thereby alleviating intracellular lipid accumulation in vitro. In addition, TSF increased SIRT1 expression and induced autophagy in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner. Moreover, SIRT1 knockdown abolished the autophagy-inducing and lipid-lowering effects of TSF. In conclusion, TSF improved lipid accumulation and hepatic steatosis by inducing the AMPK/SIRT1 pathway-mediated autophagy.

17.
Anal Chem ; 90(20): 11899-11907, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30168712

RESUMO

Oxygen deprivation is a common feature in a variety of cancer tissues and associated with tumor progression, acquisition of antiapoptotic potential, and clinical therapeutic resistance. Thus, great interest has been aroused to develop new platforms or approaches of activity assays to impact on the hypoxic microenvironment and oxygen-dependent drug responses to improve the productivity of new drug discovery. In this study, an integrated microsystem is established to combine the cytotoxic and genotoxic tests together for continuous multiple measurements under mimicking hypoxic tumor microenvironment. We fabricated a double-layer chip device by combining a single-cell-arrayed agarose layer with a microfluidics-based oxygen gradient-generating layer using a PDMS membrane. Using tirapazamine (TPZ) and blemycin (BLM) as model anticancer drugs, we demonstrated its application and performance in single cell loading, cell cultivation, and subsequent drug treatment as well as in situ analysis of oxygen-dependent cytotoxicity and genotoxicity of anticancer drugs. The results demonstrated the opposite oxygen-dependent toxicity of TPZ and BLM, which also indicated that the formation of DNA breaks is related with cell apoptosis. Compared with the traditional assays, this device takes advantage of microfluidic phenomena to generate various oxygen concentrations while exhibiting the combinatorial diversities achieved by the single cell microarray, offering a powerful tool to study single cell behaviors and responses under different oxygen conditions with desired high-content and high-throughput capabilities.


Assuntos
Antineoplásicos/farmacologia , Bleomicina/farmacologia , DNA de Neoplasias/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Técnicas Analíticas Microfluídicas , Oxigênio/metabolismo , Oxigênio/farmacologia , Tirapazamina/farmacologia , Células A549 , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Bleomicina/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , DNA de Neoplasias/genética , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Testes de Mutagenicidade , Imagem Óptica , Relação Estrutura-Atividade , Tirapazamina/química , Células Tumorais Cultivadas
18.
Biosens Bioelectron ; 120: 85-92, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30170248

RESUMO

A three-dimensional graphene-based ratiometric signal amplification aptasensor for highly sensitive and selective detection of mucin1 (MUC1) by electrochemical method has been developed. Au-reduced graphene oxide (Au-RGO) composite, which was synthesized through hydrothermal reaction and freeze-drying treatment, was used as substrate for fabricating the sensor interface on glassy carbon electrode (GCE). The application of Au-RGO is beneficial for improving electrochemical performance and immobilizing aptamer. Ferrocene labeled aptamer (Fc-Apt), grafting on Au-RGO composite, worked for specific recognition of MUC1 and as internal reference to improve the detection accuracy. Au nanoparticle modified with methyl blue labeled aptamer (MB-Apt@Au) was adopted to combine with MUC1 that captured on the electrode surface to amplify the electrical signal. Under optimal experimental conditions, this sensor was applied to detect a series concentration of MUC1 solution by alternating current voltammetry method. The aptasensor shows satisfactory detection results with a wide linear range of 1 pM to 1 µM, a low detection limit of 0.25 pM and good specificity. The good performance of the prepared electrochemical aptasensor implies that this method has potential for MUC1 detection, and it would be promising for early screening and diagnosis of cancer diseases. The proposed method also lays an important foundation for preparing ratiometric signal amplification aptasensor for other biomarkers detection.


Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas , Grafite/química , Mucina-1/análise , Ouro/química , Humanos , Limite de Detecção , Neoplasias/diagnóstico
19.
Adv Mater ; 30(14): e1705082, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29484717

RESUMO

Fiber materials with different structural features, which in many cases endow the fibers extraordinary functions, are drawing considerable attention from biomedical and material researchers. Here, perfusable necklace-like knotted microfibers are presented for the first time. Additionally, a novel microfluidic spinning method facilitates the production of variable knots and channels. Not only spindle-, but also hemisphere- and petal-knotted microfibers can be controllably fabricated. Generation and perfusion of both Janus channels and helical channel in the knotted microfibers are also shown. With no need of oil and surfactant, the spinning process is highly cytocompatible. The potential bioengineering and biomedical application of the knotted hollow microfiber is demonstrated by its cell-encapsulation feasibility and the unique liver acinus-like diffusion gradient in the knot. The merits of perfusability, cytocompatibility, and structural diversity of the microfibers may open more avenues for further material and biomedical investigation.

20.
ACS Appl Mater Interfaces ; 8(44): 29899-29905, 2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27758099

RESUMO

Given their easy structural modification and good biocompatibility advantages, near-infrared (NIR) organic dyes with a large molar extinction coefficient, while a superlow fluorescence quantum yield shows considerable potential application in photothermal therapy (PTT). Herein, a new NIR-absorbing asymmetric cyanine dye, namely, RC, is designed and synthesized via the hybrid of rhodamine and hemicyanine derivatives. RC-BSA nanoparticles (NPs) are fabricated by using the bovine serum albumin (BSA) matrix. The NPs exhibit a strong NIR absorption peak at ∼868 nm and 28.7% photothermal conversion efficiency. Based on these features, RC-BSA NPs exhibit excellent performance in ablating tumor under a 915 nm laser radiation through a PTT mechanism. These NPs show no obvious toxicity to the treated mice. Thus, RC-BSA NPs can used as a new NIR laser-triggered PTT agent in cancer treatment.


Assuntos
Corantes/química , Animais , Camundongos , Nanopartículas , Neoplasias , Fototerapia , Soroalbumina Bovina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA