RESUMEN
Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an "oxidation switch" to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases.
Asunto(s)
Cerio , Cobre , Osteoartritis , Platino (Metal) , Superóxido Dismutasa , Cerio/química , Cerio/farmacología , Cobre/química , Cobre/farmacología , Animales , Superóxido Dismutasa/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Platino (Metal)/química , Platino (Metal)/farmacología , Ratones , Oxígeno/metabolismo , Oxígeno/química , Especies Reactivas de Oxígeno/metabolismo , Catalasa/metabolismo , Catalasa/química , Humanos , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Microambiente Celular/efectos de los fármacos , MasculinoRESUMEN
The Phyllanthus emblica Linn. fruit (PEF) is a well-known medicinal and food homologous item in tropical Southeast Asian. During the drying and storing processes, some PEF will grow white frost on its surface, which is typically taken as a sign of greater quality. However, the material basis and formation mechanism of white frost on PEF surfaces are currently unclear, and there is no sufficient evidence to support the correlation between white frost on PEF surfaces and their quality. In this paper, high-performance liquid chromatography (HPLC) was used to study the differences in active ingredient content of PEF medicinal materials with and without frost. The microstructure and elemental composition of white frost were studied using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The Fourier transform infrared spectroscopy (FT-IR) was used to analysis the main functional groups in white frost. The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with UNIFI database, EDS and FT-IR results, and reference materials were used to identify the chemical composition of white frost. The exocarp of PEF before and after drying and storage was analyzed by spatial metabolomics using desorption electrospray ionization (DESI) mass spectrometry imaging system to reveal the formation mechanism of white frost on the surface of PEF. The results found that the PEF with frost have higher levels of active ingredients than those without frost. EDS and FT-IR results show that white frost is mainly composed of C, O, K elements, and contains a large number of phenolic hydroxyl, carboxyl etc. UPLC-Q-TOF-MS/MS results found that the main components of white frost were organic acids, fatty acids, and tannins, including quality markers such as gallic acid and ellagic acid etc. Spatial metabolomics research found that the white frost formation mechanism mainly involved in the ascorbate and aldarate metabolism, cutin, suberin and wax biosynthesis, citrate cycle (TCA cycle) and biosynthesis of unsaturated fatty acid. This study reveals the material basis, formation mechanism, and relationship between the surface white frost of PEF and the quality of medicinal materials, providing valuable information for the quality evaluation of PEF.
Asunto(s)
Phyllanthus emblica , Espectrometría de Masas en Tándem , Phyllanthus emblica/química , Frutas/química , Espectroscopía Infrarroja por Transformada de Fourier , Metabolómica , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Ruthenium complexes are one of the most promising anticancer drugs and ferroptosis is a novel form of regulated cell death, the study on the effect of Ru complexes on ferroptosis is helpful to find more effective antitumor drugs. Here, the synthesis and characterization of two Ru complexes containing 8-hydroxylquinoline and triphenylphosphine as ligands, [Ru(L1) (PPh3)2Cl2] (Ru-1), [Ru(L2) (PPh3)2Cl2] (Ru-2), were reported. Complexes Ru-1 â¼ Ru-2 showed good anticancer activity in Hep-G2 cells. Researches indicated that complexes Ru-1 â¼ Ru-2 could be enriched and appear as red fluorescence in the mitochondria, arouse dysfunction of mitochondria, induce the accumulation of reactive oxygen species (ROS) and lipid peroxidation (LPO), while the morphology of nuclei and cell apoptosis had no significant change. Further experiments proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in Hep-G2 cells. Remarkably, Ru-1 showed high inhibitory activity against xenograft tumor growth in vivo (TGIR = 49%). This study shows that the complex Ru-1 could act as a novel drug candidate by triggering cell ferroptosis.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Ferroptosis , Mitocondrias , Rutenio , Ferroptosis/efectos de los fármacos , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Rutenio/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones , Células Hep G2 , Especies Reactivas de Oxígeno/metabolismo , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Oxiquinolina/química , Oxiquinolina/farmacología , Peroxidación de Lípido/efectos de los fármacos , Ratones Endogámicos BALB CRESUMEN
κ-Carrageenan (κ-Car) is an important material for preparing food gels and hydrogels. However, κ-Car gel has issues with high hardness and low water-holding capacity. Modification strategy of micronization is proposed for the first time to explore its influence on texture properties and gelling process of κ-Car gel, and to investigate the feasibility of κ-Car as a food matrix with low strength. κ-Car undergoing 60 min of micronization, the d(0.9) decreased by 79.33 %, SBET and Vtotal increased by 89.23 % and 95.27 %. The swelling rate and degree of gelling process increased significantly, and the microstructure changed from loose large pores to dense small pores resembling a "honeycomb". Importantly, the hardness of gel-60, Milk-60 and PNS-60 decreased by 72.52 %, 49.25 % and 81.37 %. In addition, WHC of gel-60, Milk-60 and PNS-60 was improved. IDDSI tests showed that κ-Car gels, milk gels and PNS gels can be categorized as level 6 (soft and bite-sized), except for PNS-60, which belongs to level 5 (crumbly and moist). Furthermore, the texture and bitter masking effect of milk gels and PNS gels were improved. In conclusion, this study demonstrated that micronization can be a novel approach to improve the gel properties of κ-Car, laying the groundwork for developing dysphagia foods.
Asunto(s)
Carragenina , Geles , Carragenina/química , Geles/química , Deglución , Leche/química , Animales , Dureza , Administración Oral , Hidrogeles/químicaRESUMEN
Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π-π interaction to prepare g-C3N4-loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt-N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g-C3N4-loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage invitro and an OA joint model invivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.