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1.
Neurochem Int ; 177: 105764, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38729355

RESUMO

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.


Assuntos
Deslocamento do Disco Intervertebral , Oligopeptídeos , Estresse Oxidativo , Ratos Sprague-Dawley , Ciática , Animais , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Deslocamento do Disco Intervertebral/metabolismo , Ratos , Oligopeptídeos/farmacologia , Ciática/metabolismo , Ciática/tratamento farmacológico , Masculino , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Vértebras Lombares , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Receptores Opioides mu/metabolismo
2.
J Mater Chem B ; 12(16): 4018-4028, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38578014

RESUMO

On-demand controlled drug release holds great promise for cancer therapy. Light-degradable nanocarriers have gained increasing attention for designing controllable drug delivery systems owing to their spatiotemporally controllable properties. Herein, a highly luminescent and light-degradable nanocarrier is constructed by intercalating glutathione-capped gold nanoclusters (AuNCs) into zeolitic imidazolate framework-8 (ZIF-8) via competitive coordination assembly, named AuNC@ZIF-8, for light-triggered drug release. Glutathione-capped AuNCs and 2-methylimidazole (MIm) competitively coordinated with Zn2+ to form AuNC@ZIF-8 using a one step process in an aqueous solution. Specifically, the obtained AuNC@ZIF-8 has a high quantum yield of 52.96% and displays a distinctive property of photolysis. Competitive coordination interactions within AuNC@ZIF-8 were evidenced by X-ray diffraction and X-ray photoelectron spectroscopy, in which Zn2+ strongly coordinated with the N of MIm and weakly coordinated with the carboxyl/amino groups in the glutathione of AuNCs. Under light irradiation, the Au-S bond in AuNCs breaks, enhancing the coordination ability between carboxyl/amino groups and Zn2+. This collapses the crystal structure of AuNC@ZIF-8 and causes subsequent fluorescence quenching. Additionally, AuNC@ZIF-8 is successfully employed as a luminescent nanocarrier of anticancer drugs to form drug-AuNC@ZIF-8, in which three typical anticancer drugs are selected due to different coordination interactions. The obtained smart drug-AuNC@ZIF-8 can be effectively internalized into HeLa cells and degraded in response to blue light, with negligible dark cytotoxicity and high light cytotoxicity. This study highlights the crucial role of competitive coordination interactions in synthesizing functional materials with fluorescence efficiency and photolytic properties.


Assuntos
Liberação Controlada de Fármacos , Ouro , Luz , Nanopartículas Metálicas , Estruturas Metalorgânicas , Ouro/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Humanos , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Células HeLa , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Tamanho da Partícula , Propriedades de Superfície , Doxorrubicina/química , Doxorrubicina/farmacologia
3.
Inflammopharmacology ; 32(3): 1659-1704, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38520574

RESUMO

Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as "Ezhu" in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases. Pharmacokinetic studies have shown that Cur is rapidly distributed in almost all organs of rats after intragastric administration with high concentrations in the small intestine and colon. Several studies focusing on structure-activity relationship (SAR) of Cur have shown that some Cur derivatives, chemically modified at C-8 or C-14, exhibited more potent anti-cancer activity and lower toxicity than Cur itself. This review aims to comprehensively summarize the latest advances in the pharmacological and pharmacokinetic properties of Cur in the last decade with a focus on its anti-cancer and hepatoprotective potentials, as well as the research progress in drug delivery system and potential applications of Cur to date, to provide researchers with the latest information, to highlighted the limitations of relevant research at the current stage and the aspects that should be addressed in future research. Our results indicate that Cur and its derivatives could serve as potential novel agents for the treatment of a variety of diseases, particularly cancer and liver diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Sesquiterpenos , Animais , Sesquiterpenos/farmacologia , Sesquiterpenos/farmacocinética , Sesquiterpenos/administração & dosagem , Humanos , Relação Estrutura-Atividade , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem
4.
Entropy (Basel) ; 20(7)2018 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-33265577

RESUMO

FeSiBAlNi (W5), FeSiBAlNiCo (W6-Co), and FeSiBAlNiGd (W6-Gd) high entropy alloys (HEAs) were prepared using a copper-mold casting method. Effects of Co and Gd additions combined with subsequent annealing on microstructures and magnetism were investigated. The as-cast W5 consists of BCC solid solution and FeSi-rich phase. The Gd addition induces the formation of body-centered cubic (BCC) and face-centered cubic (FCC) solid solutions for W6-Gd HEAs. Whereas, the as-cast W6-Co is composed of the FeSi-rich phase. During annealing, no new phases arise in the W6-Co HEA, indicating a good phase stability. The as-cast W5 has the highest hardness (1210 HV), which is mainly attributed to the strengthening effect of FeSi-rich phase evenly distributed in the solid solution matrix. The tested FeSiBAlNi-based HEAs possess soft magnetism. The saturated magnetization and remanence ratio of W6-Gd are distinctly enhanced from 10.93 emu/g to 62.78 emu/g and from 1.44% to 15.50% after the annealing treatment, respectively. The good magnetism of the as-annealed W6-Gd can be ascribed to the formation of Gd-oxides.

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