RESUMO
Exosomes (Exo) generated from mesenchymal stem cells (MSCs) have great therapeutic potential in ischemia-reperfusion treatment. For best therapeutic effect, high quality Exo product and effective delivery system are indispensable. In this study, we developed a new strategy for ischemia-reperfusion recovery by combining MSCs 3D (3D-MSC) culturing technology to generate Exo (3D-MSC-Exo) and microneedle for topical delivery. Firstly, primary MSCs from neonatal mice were isolated and 3D cultured with gelatin methacryloyl (GelMA) hydrogel to prepare 3D-MSC-Exo. The 3D-MSC showed better viability and 3D-MSC-Exo exhibited more effective effects of reducing neuroinflammation, inhibiting glial scarring, and promoting angiogenesis. Subsequently, the biocompatible GelMA was used to construct microneedles for 3D-Exo delivery (GelMA-MN@3D-Exo). The results demonstrated GelMA microneedles had excellent 3D-Exo loading capacity and enabled continuous 3D-Exo release to maintain effective therapeutic concentrations. Furthermore, the rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic effect of GelMA-MN@3D-Exo in ischemia-reperfusion in vivo. Animal experiments showed that the GelMA-MN@3D-Exo system could effectively reduce the local neuroinflammatory reaction, promote angiogenesis and minimize glial scar proliferation in ischemia-reperfusion. The underlying reasons for the stronger neuroprotective effect of 3D-Exo was further studied using mass spectrometry and transcriptome assays, verifying their effects on immune regulation and cell proliferation. Taken together, our findings demonstrated that GelMA-MN@3D-Exo microneedle can effectively attenuate ischemia-reperfusion cell damage in the MCAO model, which provides a promising therapeutic strategy for ischemia-reperfusion recovery.
Assuntos
Exossomos , Gelatina , Células-Tronco Mesenquimais , Agulhas , Traumatismo por Reperfusão , Animais , Gelatina/química , Camundongos , Ratos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/terapia , Metacrilatos/química , Masculino , Modelos Animais de Doenças , Hidrogéis/química , Ratos Sprague-Dawley , Infarto da Artéria Cerebral Média/terapiaRESUMO
Zinc oxide (ZnO) nanophotocatalyst is a promising candidate for degrading organic pollutants but has an extremely low photocatalytic activity under nature sunlight. In this work, flower-like MoS2 quantum dots/ZnO (MQ/ZnO) nanospheres with the size of approximately 1.26⯵m are prepared at low temperature. The resultant flower-like MQ/ZnO nanospheres displayed higher photocatalytic activity than pure ZnO nanospheres under natural sunlight and without stirring, with the decomposition rate of the MQ/ZnO composites approximately 3.3 times higher than that of the pure ZnO nanospheres. Furthermore, the introduction of MoS2 QDs endowed ZnO nanospheres with optical memory ability. The enhanced sunlight-driven photocatalytic activity is dependent on the unique electrical properties of MoS2 QDs and the synergistic effect between ZnO and MoS2 QDs.
RESUMO
OBJECTIVE: To investigate the apoptotic effect of oridonin in human pancreatic cancer cells PANC-1, and to explore the underlying mechanism. METHODS: MTT assay was used to measure the cell viability. Apoptosis was determined by confocal laser scanning microscope after Hoechst 33342 staining and flow cytometry analysis after PI staining. The regulation of JNK and p38 MAPK signaling pathway proteins was examined by Western blot analysis. RESULTS: Treatment with oridonin for 24 h resulted in a marked decrease in cell viability in a dose-dependent manner. The IC50 value was determined as 49.80 µmol/L for 24 h. After treatment with 50 micromol/L and 80 µmol/L oridonin for 24 h, typical apoptotic nucleus alterations were observed with confocal laser scanning microscope and apoptotic rates of PANC-1 cells increased by flow cytometry analysis. Treatment with 80 µmol/L oridonin down-regulated protein expression of JNK, p38 and increased the expression of p-JNK, p-p38. Furthermore, 80 µmol/L oridonin treatment decreased the expression of down-stream proteins Caspase-9, Caspase-3 and PARP in the apoptotic pathway as well as activated the cleavage of Caspase-9. CONCLUSION: Oridonin can induce apoptosis of PANC-1 cells through JNK and p38 MAPK pathway proteins.