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1.
Front Chem ; 11: 1200490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284581

RESUMO

Glycogen synthase kinase-3 (GSK3ß), a serine/threonine protein kinase, has been discovered as a novel target for anticancer drugs. Although GSK3ß is involved in multiple pathways linked to the etiology of various cancers, no specific GSK3ß inhibitor has been authorized for cancer therapy. Most of its inhibitors have toxicity effects therefore, there is a need to develop safe and more potent inhibitors. In this study, a library of 4,222 anti-cancer compounds underwent rigorous computational screening to identify potential candidates for targeting the binding pocket of GSK3ß. The screening process involved various stages, including docking-based virtual screening, physicochemical and ADMET analysis, and molecular dynamics simulations. Ultimately, two hit compounds, BMS-754807 and GSK429286A, were identified as having high binding affinities to GSK3ß. BMS-754807 and GSK429286A exhibited binding affinities of -11.9, and -9.8 kcal/mol, respectively, which were greater than that of the positive control (-7.6 kcal/mol). Further, molecular dynamics simulations for 100 ns were employed to optimize the interaction between the compounds and GSK3ß, and the simulations demonstrated that the interaction was stable and consistent throughout the study. These hits were also anticipated to have good drug-like properties. Finally, this study suggests that BMS-754807 and GSK429286A may undergo experimental validation to evaluate their potential as cancer treatments in clinical settings.

2.
Zhongguo Zhen Jiu ; 43(2): 203-6, 2023 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-36808516

RESUMO

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Meridianos , Humanos , Medicina Tradicional Chinesa , Deslocamento do Disco Intervertebral/terapia , Terapia por Acupuntura/métodos , Procedimentos Cirúrgicos Vasculares , Pontos de Acupuntura
3.
J Biomed Nanotechnol ; 15(11): 2262-2270, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31847940

RESUMO

Gold nano rods (GNRs) have showed cytotoxicity to cancer cells. At the same time, it shows little effects on non-tumor cells. Between GNRs and sub-cellular organelles, the understanding of interaction plays a very important role to determine the intracellular mechanisms. The purpose of what we done is to explain the effects of the surface properties of GNRs on specific cancer cell death. Three GNR samples with different aspect ratios were finely prepared by the seed-mediated growth method. Then the intracellular transport and the in vitro/vivo mechanisms of cancer cell death were studied by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser light scattering, and flow cytometry (FCM). It was found that GNRs700 exhibited the largest photothermal conversion efficiency. However, the GNR660 with or without light stimulation exhibited the highest cytotoxicity against cancer cells, which was contradict to the general knowledge. Detailed intracellular investigations showed that the lysosome was the key sub-organelle affecting the GNR function. Further experiments revealed that cytotoxicity was strongly affected by the GNR's surface potential. This potential was actually related to the density of surface cationic molecules, which further regulated lysosomal membrane penetration. The results obtained herein indicated that the physicochemical properties of the surface potential mediated the specific toxicity of GNRs against tumours.


Assuntos
Ouro , Nanotubos , Linhagem Celular Tumoral , Humanos , Lasers , Propriedades de Superfície
4.
Nanomedicine (Lond) ; 12(4): 295-315, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28093940

RESUMO

AIM: To target both head and neck squamous cell carcinoma (HNSCC) cells and cancer stem cells (CSCs) by salinomycin-loaded DSPE-PEG-MTX (synthesized using DSPE-PEG2000-NH2 and methotrexate) nanomicelles (M-SAL-MTX). MATERIALS & METHODS: The characterization, antitumor activity and mechanism of M-SAL-MTX were evaluated. RESULTS & CONCLUSION: M-SAL-MTX showed enhanced inhibitory effect toward both HNSCC CSCs and non-CSCs compared with a single treatment of methotrexate and salinomycin. In nude mice-bearing HNSCC xenografts, M-SAL-MTX suppressed tumor growth more effectively than other controls including combination of methotrexate and salinomycin. Therefore, M-SAL-MTX may provide a strategy for treating HNSCC by targeting both HNSCC CSCs and HNSCC cells.


Assuntos
Antibacterianos/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Portadores de Fármacos/química , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Piranos/administração & dosagem , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Células-Tronco Neoplásicas/patologia , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Piranos/farmacologia , Piranos/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço
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