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Macrophages play a vital role for guiding the fate of osteogenesis- related cells. It is well known that nano-topography and bioactive ions can directly enhance osteogenic behavior. However, the effects of nano-structure combined with bioactive ions release on macrophage polarization and the following osteogenesis and angiogenesis are rarely reported. Herein, Mg(OH)2 films with nano-sheet structures were constructed on the surface of Ti using hydrothermal treatment. The film presented nano-sheet topography and sustained release of Mg ions. The results of in vitro culture of bone marrow-derived macrophages (BMDMs), including PCR, western blot and flow cytometry suggested that the nano-Mg(OH)2 films were more favorable for macrophages polarizing to tissue healing M2 phenotype. Moreover, air-pouch model confirmed that the nano-Mg(OH)2 film coated Ti would induce milder inflammation and thinner fibrous layer in vivo, compared with untreated Ti. Furthermore, macrophages-conditioned culture mediums were collected from nano-Mg(OH)2 coated Ti group was superior for the osteogenic behaviors of mice bone marrow stem cells and the angiogenic behaviors of human umbilical vein endothelial cells. With harmonious early inflammatory response and subsequently improved osteogenesis and angiogenesis, the nano-Mg(OH)2 coated Ti is promising for orthopedic applications.
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Paclitaxel has been extensively used in clinics for cancer treatment. However, its limited solubility in aqueous solution and high occurrence of side effects have also been widely reported. In this study, we constructed a biocompatible RNA nanoparticle delivery system (3WJ-EGFRapt) that includes 3WJ (3-way junction) nanoparticle with a size of 4.85 ± 0.59 nm as a backbone and an EGFR (epidermal growth factor receptor) aptamer for specific targeting to chordomas cells, which owns the encapsulation ability of drug paclitaxel (PTX) for cancer therapy. Confocal microscopy and flow cytometry results confirmed 3WJ-EGFRapt nanoparticle exhibited excellent specific targeting to chordomas cell U-CH2 which is an EGFR(+) cell line; while the 3WJ nanoparticle lose the targeted ability. Both of the two nanoparticles own no sensitivity to lung cancer cell H520 which is an EGFR(-) cell line. Moreover, the 3WJ-EGFRapt nanoparticle encapsulated drug PTX could enhance the inhibition efficiency of chordomas tumor cells U-CH2 as compared to free PTX alone. This work demonstrates that RNA-3WJ constructed with a targeting aptamer provides a compromising targeted drug delivery ability on chordomas cells for therapeutics.
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Antineoplásicos , Aptámeros de Nucleótidos , Cordoma , Nanopartículas , Antineoplásicos/farmacología , Línea Celular Tumoral , Cordoma/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Receptores ErbB/genética , Humanos , Paclitaxel , ARNRESUMEN
Dysphagia is one of the most common complaints after anterior cervical spine surgery. The Bazaz scale, the Dysphagia Short Questionnaire (DSQ), and the Hospital for Special Surgery-Dysphagia and Dysphonia Inventory (HSS-DDI) were patient-reported outcome measures assessing the patients' perceptions of their swallowing functions after surgery. This prospective diagnostic test study aimed to compare these surveys' psychometric properties in the Chinese population. We evaluated 150 consecutive patients after anterior cervical spine surgery with the Bazaz scale, DSQ, HSS-DDI, and M.D. Anderson Dysphagia Inventory (MDADI). The reliability and validity of the Bazaz scale, DSQ, and HSS-DDI were compared. Receiver operating characteristic (ROC) curves of the DSQ, Bazaz scale, and HSS-DDI were constructed using the MDADI as a reference criterion. Their areas under the curve (AUCs) were further analyzed. In total, 132 participants completed all of the surveys. The results showed that all surveys were significantly correlated with each other. The HSS-DDI and HSS-Dysphagia subscale showed near-perfect reliability (Cronbach α = 0.969 and 0.957, respectively). ROC curves showed both HSS-DDI and HSS-Dysphagia subscale had greater accuracy (AUCs > 0.9) in detecting mild dysphagia and moderate/severe dysphagia. The HSS-Dysphagia subscale achieved higher accuracy in assessing the dysphagia symptoms after anterior cervical spine surgery. The Bazaz scale was considered less accurate than other scales. Our results provided guidance for selecting the appropriate measuring tool during clinical and research practices.
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Trastornos de Deglución , Disfonía , Fusión Vertebral , Vértebras Cervicales/cirugía , China , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Disfonía/diagnóstico , Disfonía/etiología , Hospitales , Humanos , Complicaciones Posoperatorias/diagnóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
[This corrects the article DOI: 10.1155/2020/7073805.].
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BACKGROUND: Osteoporosis is a systemic bone disease resulting from decreased bone mass and bone microstructure degeneration. Yes-associated protein 1 (YAP1) belongs to YAP family and plays a significant part in controlling bone quality. AIM OF THE STUDY: Present study aimed to study the function and up-stream mechanism of YAP1 in the differentiation of BMSCs (bone marrow stromal cells) and MC3T3-E1. METHODS: ALP staining, alizarin red staining and western blot analysis of osteogenic biomarkers determined osteogenic differentiation in BMSCs and MC3T3-E1. Mechanistic assays including luciferase reporter assay, RIP assay and RNA pull down assay disclosed the interplays between RNAs. RESULTS: YAP1 promoted osteogenic differentiation of BMSCs and MC3T3-E1. Circ_0024097 originated from YAP1 sponged miR-376b-3p to elevate YAP1 expression in BMSCs and MC3T3-E1. Further, YAP1 mediated circ_0024097- promoted effects on osteogenic differentiation. Moreover, circ_0024097 activated Wnt/ß-catenin pathway to facilitate osteogenic differentiation. CONCLUSION: It was firstly uncovered in present study that circ_0024097 attenuated osteoporosis through promoting osteogenic differentiation via miR-376b-3p/YAP1 axis and Wnt/ß-catenin pathway.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/metabolismo , Osteogénesis , Osteoporosis/metabolismo , Vía de Señalización Wnt , Células 3T3 , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Proteínas de Ciclo Celular/genética , Células Madre Mesenquimatosas/patología , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Osteoblastos/patología , Osteoporosis/genética , Osteoporosis/patología , ARN Circular/genética , ARN Circular/metabolismo , Regulación hacia Arriba , Proteínas Señalizadoras YAPRESUMEN
Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.
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It was well established that long non-coding RNAs (LncRNAs) could serve as oncogene or tumor suppressor in terms of the tumor type. FTX, as a member of lncRNA family, has been reported to be associated with several tumor progressions, such as hepatocellular carcinoma (HCC), renal cell carcinoma (RCC) and colorectal cancer. However, the regulatory role of FTX in osteosarcoma (OS) still lacks research analysis. This paper aims to explore how FTX exerts its regulatory role on OS by modulating TXNRD1/miR-320a, so as to provide a novel lncRNA theoretical framework for the diagnosis and treatment of OS. QRT-PCR revealed that FTX and TXNRD1 were abnormally upregulated in OS, whereas miR-320a expression was significantly decreased. Luciferase reporter analysis showed that both FTX and TXNRD1 could combine with miR-320a. A series of functional experiments indicated that knockdown of FTX could suppress OS cell proliferation and migration, while facilitating apoptosis ability simultaneously. However, TXNRD1 overexpression or miR-320a inhibition could rescue the oncogenic function of FTX. Taken all the experiment results together, this paper indicated that FTX impacted osteosarcoma cell proliferation and migration by modulating TXNRD1/miR-320a.
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Neoplasias Óseas/patología , Movimiento Celular , Proliferación Celular , MicroARNs/genética , Osteosarcoma/patología , ARN Largo no Codificante/genética , Tiorredoxina Reductasa 1/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Pronóstico , ARN Largo no Codificante/antagonistas & inhibidores , Tiorredoxina Reductasa 1/genética , Células Tumorales CultivadasRESUMEN
BACKGROUND: The purpose of this study is to explore the therapeutic effect of percutaneous kyphoplasty (PKP) combined with anti-osteoporosis drug, zoledronic acid, on postmenopausal women with osteoporotic vertebral compression fracture (OVCF) and to perform an analysis of postoperative bone cement leakage risk factors. METHODS: A total of 112 OVCF patients, according to therapeutic regimens, were divided into control group (n = 52, treated with PKP) and observation group (n = 60, treated with PKP and zoledronic acid injection). RESULTS: Postoperative tumor necrosis factor-α and interleukin-6 levels were significantly decreased in the two groups, compared with those before treatment (both P < 0.05); bone mineral density (BMD), serum bone gla protein (BGP), and vertebral height ratio of injured vertebrae were significantly increased, and procollagen type I N-terminal propeptide (PINP), Cobb angle, visual analogue scale/score (VAS), and Oswestry disability index (ODI) were significantly decreased compared with those before treatment (all P < 0.05). There were significantly higher changes in difference value of BMD, PINP, BGP, vertebral height ratio of injured vertebrae, Cobb angle, VAS, and ODI levels and significantly better therapeutic effect in the observation group than those in the control group (all P < 0.05). Multivariate logistic regression analysis showed that the use of zoledronic acid, vertebral height ratio of injured vertebrae, and ODI were independent factors affecting the therapeutic effect, and that the dosage of bone cement, and peripheral vertebrae wall damage were independent risk factors causing postoperative bone cement leakage. There were no significant differences in postoperative bone cement leakage rate between the two groups. CONCLUSIONS: Peripheral vertebrae wall damage and the dosage of bone cement are independent risk factors causing bone cement leakage in OVCF patients treated with PKP. PKP combined with zoledronic acid has an improvement effect on the condition of postmenopausal women with OVCF and reduces the inflammation and pain in patients, which is beneficial to clinical treatment.
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Cementos para Huesos/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Fracturas por Compresión/cirugía , Cifoplastia/métodos , Osteoporosis/tratamiento farmacológico , Fracturas Osteoporóticas/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Fracturas de la Columna Vertebral/cirugía , Ácido Zoledrónico/uso terapéutico , Estudios de Cohortes , Terapia Combinada , Femenino , Fracturas por Compresión/etiología , Humanos , Persona de Mediana Edad , Osteoporosis/complicaciones , Fracturas Osteoporóticas/etiología , Posmenopausia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Fracturas de la Columna Vertebral/etiologíaRESUMEN
The functions of long (>200 nt) non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) have only been investigated in cancer biology. We found that plasma LncRNA SNHG1 was down-regulated in postmenopausal than in premenopausal females. Among postmenopausal females, the ones with postmenopausal osteoporosis showed much lower expression levels of plasma lncRNA SNHG1. A 6-year follow-up study on postmenopausal females revealed that plasma lncRNA SNHG1 decreased in females with postmenopausal osteoporosis but not in healthy postmenopausal females. Levels of plasma lncRNA SNHG1 at 12 months before diagnosis is sufficient to distinguish postmenopausal osteoporosis patients from healthy controls. After treatment, plasma lncRNA SNHG1 were significantly up-regulated. Therefore, lncRNA SNHG1 was down-regulated after menopause and plasma level of lncRNA SNHG1 may serve as a biomarker for the diagnosis and treatment of postmenopausal osteoporosis.
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Regulación hacia Abajo/genética , Menopausia/genética , Osteoporosis Posmenopáusica/genética , ARN Largo no Codificante/genética , Adulto , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Regulación hacia Arriba/genéticaRESUMEN
Osteosarcoma is a malignant tumor of the skeletal system. The zinc finger transcription factor ZIC2 has been reported to be highly expressed in human cancers. The present study evaluated the effects of ZIC2 and the possible underlying mechanisms in the human osteosarcoma cells. The expression levels of ZIC2 in human fetal osteoblastic cell line (hFOB1.19), osteosarcoma cell lines (U-2OS, SaoS2, and MG63), normal bone tissue, and osteosarcoma tumor were analyzed by Western blot, and real-time quantitative RT-PCR (qRT-PCR). Osteosarcoma cells with either overexpressed ZIC2 or suppressed ZIC2 were analyzed to determine cell viability, colony formation, and cell invasion. The expressions of SHIP2 and PI3K/AKT signal pathway-related proteins were analyzed by Western blot and qRT-PCR. We first showed that ZIC2 is highly expressed in osteosarcoma cells and tissues. Then we demonstrated that overexpression of ZIC2 promoted viability, migration, and invasion of osteosarcoma cells, whereas suppression of ZIC2 showed opposite effects. Furthermore, SHIP2 expression was negatively regulated by ZIC2. Importantly, ZIC2 overexpression activated the PI3K/AKT signal pathway; however, overexpressed SHIP2 inhibited these effects. Lastly, we showed that activation of the PI3K/AKT signal pathway is essential for the effects of ZIC2 on osteosarcoma cells, as the effects of ZIC2 on the osteosarcoma cells were reversed by a PI3K/AKT inhibitor. Overall, ZIC2 is highly expressed in osteosarcoma cells and tissues, and its overexpression promotes viability, invasion of osteosarcoma cells via SHIP2 suppression, and PI3K/AKT activation. Thus, ZIC2 can be considered as a novel drug target for osteosarcoma management.