Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Adv Healthc Mater ; 12(32): e2301724, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37767893

RESUMEN

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.


Asunto(s)
Fibroínas , Andamios del Tejido , Ratas , Animales , Andamios del Tejido/química , Fibroínas/química , Osteogénesis , Calcio , Biomimética , Calmodulina , Regeneración Ósea/fisiología , Fenómenos Magnéticos , Ingeniería de Tejidos/métodos
2.
J Orthop Res ; 41(7): 1555-1564, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36448180

RESUMEN

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.


Asunto(s)
Degeneración del Disco Intervertebral , Núcleo Pulposo , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/fisiología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/uso terapéutico , Fosfatidilinositol 3-Quinasas , Núcleo Pulposo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/uso terapéutico , Estrés Oxidativo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Apoptosis
3.
Cell Biol Int ; 46(10): 1588-1603, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35762224

RESUMEN

To provide a basis for promising exosome-based therapies against intervertebral disc degeneration (IDD), our present research aimed to identify a mechanism underlying the vesicle release from nucleus pulposus cells (NPCs). Scutellarin (SC) is a natural chemotherapeutic agent isolated from Erigeron breviscapus with a variety of biological activities. Here, we observed the significantly elevated autophagy levels in rat NPCs under the stimulation of SC, leading to a concomitant enhancement of intracellular vesicle release, which could be attributed to the inactivation of the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (Akt) pathway. To ensure that exosome release was driven by SC via the autophagic pathway, we implemented gain-of-function and loss-of-function studies by additionally using insulin-like growth factor-1 (IGF-1) and small-interfering RNA of autophagy-related gene 5 (ATG5), and the exosome secretion decreased in the case of attenuated autophagy. Evidently, the treatment with SC exerted the remarkable upregulation of Rab8a through the overexpression of ATG5. After the respective knockdown of ATG5 and Rab8a, the increased release of exosomes induced by SC was reversed, whereas the number of intracellular vesicles was restored. Overall, it can be concluded that SC contributes to the autophagy activation in NPCs by acting on the PI3K/PTEN/Akt pathway, which upregulates the expression of Rab8a and promotes the release of exosomes, inspiring novel therapeutic strategies in preventing IDD that might be fruitfully investigated.


Asunto(s)
Exosomas , Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Apigenina , Apoptosis/genética , Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Exosomas/metabolismo , Glucuronatos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas
4.
Clin Neurol Neurosurg ; 214: 107154, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35151059

RESUMEN

OBJECTIVE: re is paucity in the literature on the epidemiological evidence of pulmonary thromboembolism (PE) and deep venous thrombosis (DVT) in spinal metastatic tumor patients. The aim of our study was to identify the incidence and risk factors for VTE in spinal metastasis patients treated with decompression with internal instruments. METHODS: We prospectively investigated the occurrence of VTE after decompression with internal fixations in 80 spinal metastasis patients. DVT was diagnosed by using a duplex ultrasonographical. PE was diagnosed by multidetector computed tomographic (CT) pulmonary angiography. Patient information and clinical parameters were collected. Risk factors were analyzed by comparing the difference between VTE and non-VTE cases. RESULTS: The incidence of developing a DVT was 6.3% (5/80). No patient suffered PE. In univariate analysis, the mean length of hospital stay after surgery until discharge for VTE group was longer than non-VTE group, ODI scores and AIS in VTE group were significantly worse than non-VTE group, D-dimer one-day postoperatively for VTE group was significantly higher than non-VTE group. In logistic regression, D-dimer at one-day postoperatively was the only risk factor. The areas under the ROC curves for the D-dimer (post) to distinguish between non-VTE and VTE was 0.971(P value=0.000). By means of the ROC analysis, the optimum thresholds of D-dimer(post) were determined to be 9.51 mg/L. The sensitivity and specificity for the optimum threshold were 100.0% and 92.0%. CONCLUSION: The prospective study of 80 patients with spinal metastasis who underwent decompression with internal fixation revealed an incidence of DVT of 6.3%, patients with increasingly D-dimer level at one-day postoperatively had a higher risk of DVT, and the optimum thresholds of D-dimer(post) were determined to be 9.51 mg/L.


Asunto(s)
Embolia Pulmonar , Neoplasias de la Columna Vertebral , Tromboembolia Venosa , Descompresión/efectos adversos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Incidencia , Prevalencia , Estudios Prospectivos , Embolia Pulmonar/epidemiología , Factores de Riesgo , Neoplasias de la Columna Vertebral/complicaciones , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología
5.
Ann Transl Med ; 9(17): 1376, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34733928

RESUMEN

BACKGROUND: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism. METHODS: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs. RESULTS: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings. CONCLUSIONS: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...