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1.
Int Immunopharmacol ; 134: 112161, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728878

RESUMO

Intervertebral disc degeneration (IVDD) is a leading cause of degenerative spinal disorders, involving complex biological processes. This study investigates the role of the kallikrein-kinin system (KKS) in IVDD, focusing on the protective effects of bradykinin (BK) on nucleus pulposus cells (NPCs) under oxidative stress. Clinical specimens were collected, and experiments were conducted using human and rat primary NPCs to elucidate BK's impact on tert-butyl hydroperoxide (TBHP)-induced oxidative stress and damage. The results demonstrate that BK significantly inhibits TBHP-induced NPC apoptosis and restores mitochondrial function. Further analysis reveals that this protective effect is mediated through the BK receptor 2 (B2R) and its downstream PI3K/AKT pathway. Additionally, BK/PLGA sustained-release microspheres were developed and validated in a rat model, highlighting their potential therapeutic efficacy for IVDD. Overall, this study sheds light on the crucial role of the KKS in IVDD pathogenesis and suggests targeting the B2R as a promising therapeutic strategy to delay IVDD progression and promote disc regeneration.


Assuntos
Apoptose , Bradicinina , Degeneração do Disco Intervertebral , Núcleo Pulposo , Estresse Oxidativo , Ratos Sprague-Dawley , terc-Butil Hidroperóxido , Animais , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/patologia , Núcleo Pulposo/metabolismo , terc-Butil Hidroperóxido/toxicidade , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/patologia , Humanos , Masculino , Bradicinina/farmacologia , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Células Cultivadas , Receptor B2 da Bradicinina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Feminino , Microesferas , Transdução de Sinais/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças
2.
ChemSusChem ; 14(20): 4573-4582, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34378343

RESUMO

In-situ electro-polymerization of redox-active monomers has been proved to be a novel and facile strategy to prepare polymer electrodes with superior electrochemical performance. The monomer molecular structure would have a profound impact on electro-polymerization behavior and thus electrochemical performance. However, this impact is poorly understood and has barely been investigated yet. Herein, three carbazole-based monomers, 9-phenylcarbazole (CB), 1,4-bis(carbazol-9-yl)benzene (DCB), and 2,6-bis(carbazol-9-yl)naphthalene (DCN), were applied to study the above issue systematically and achieve excellent long cycle performance. The monomers were rationally designed with different polymerizable sites and solubilities. It was found that a monomer with increased polymerizable sites and decreased solubility brought about enhanced electrochemical performance. This is because poor solubility could enhance utilization of the monomer for polymerization and more polymerizable sites could lead to a stable crosslinked polymer network after electro-polymerization. DCN with four polymerizable sites and the poorest solubility displayed the best electrochemical performance, which showed stable cycling up to 5000 cycles with high capacity retention of 76.2 % (among the best cycle in the literature). Our work for the first time reveals the relationship between monomer structure and in-situ electro-polymerization behavior. This work could shed light on the structure design/optimization of monomers for high-performance polymer electrodes prepared through in-situ electro-polymerization.

3.
Small ; 17(22): e2006424, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33734586

RESUMO

Metal-organic frameworks (MOFs) and their derivatives have attracted enormous attention in the field of energy storage, due to their high specific surface area, tunable structure, highly ordered pores, and uniform metal sites. Compared with the wide research of MOFs and their related materials on anode materials for alkali metal ion batteries, few works are on cathode materials. In this review, design principles for promoting the electrochemical performance of MOF-related materials in terms of component/structure design, composite fabrication, and morphology engineering are presented. By summarizing the advancement of MOFs and their derivatives, Prussian blue and its analogs, and MOF surface coating, challenges and opportunities for future outlooks of MOF-related cathode materials are discussed.

4.
ACS Appl Mater Interfaces ; 12(6): 7179-7185, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31967452

RESUMO

In this work, a 9,10-anthraquinone (AQ) derivative functionalized by two methoxy groups, 2,6-dimethoxy-9,10-anthraquinone (DMAQ), was synthesized and its electrochemical performance was comprehensively studied with different electrolyte concentrations. Density functional theory (DFT) calculations demonstrate that there exists a conjugation effect between oxygen atoms of methoxy groups and the AQ skeleton, which could extend the conjugate plane and increase intermolecular interaction. As a result, DMAQ shows considerably reduced solubility in ether solvent/electrolyte and greatly enhanced cycling performance compared with those of AQ. Interestingly, it is found that the electrolyte concentration plays an important role in determining the electrochemical performance. Cycling under a relatively low (2 M) or high (6 M) concentration electrolyte of lithium bis(trifluoromethanesulfonyl)imide in a mixture solvent of 1,3-dioxolane and 1,2-dimethoxyethane (1/1, v/v) displays unsatisfied cell performance. While a moderate electrolyte concentration of 4 M delivers the highest initial capacity and the best cycling stability. The work would shed light on the rational molecular structure design and electrolyte concentration optimization for achieving the high electrochemical performance of organic electrode materials.

5.
ChemSusChem ; 13(9): 2436-2442, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31840438

RESUMO

Conjugated carbonyl-based organic electrode materials for lithium-ion batteries have gained increasing interests owing to their many advantages such as resource abundance and sustainable development. However, serious dissolution in organic liquid electrolytes is often encountered, resulting in inferior electrochemical performance such as poor cycling stability. Herein, a new molecular design strategy was developed to address the dissolution issue of 9,10-anthraquinone (AQ). An AQ dimer with near-plane molecular structure, 1,4-bis(9,10-anthraquinonyl)benzene (BAQB), was facilely synthesized. The near-plane structure was proved by DFT calculations. It was found that the obtained BAQB was insoluble in ether electrolyte. Compared to AQ, BAQB displayed remarkably enhanced cycling stability. After 100 cycles at 0.2 C, a high capacity retention of 91.6 % was achieved (195 mAh g-1 ). BAQB also exhibited excellent rate performance (138 mAh g-1 at 10 C). The results demonstrate the effectiveness of the near-plane molecular design concept. This work provides a new idea for rational molecular design to inhibit the dissolution of conjugated carbonyl-based organic electrode materials.

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