RESUMEN
Osteosarcoma (OS) is the most common primary malignant bone tumor and is mainly diagnosed in children. Toll-like receptor 9 (TLR9) is expressed in various tumor cells and was correlated with cancer progression. However, the underlying mechanism of TLR9 on the OS progression remains unclear. Our previous study demonstrated that the expression of TLR9 was positively correlated with the development stage of OS. Herein, we further evaluated the actual roles and the molecular mechanism of TLR9 on regulating OS cell proliferation and metastasis. Our data showed that TLR9 was upregulated in OS cells compared to normal osteoblastic cells, and knockdown of TLR9 inhibited OS cell proliferation and induced cell cycle arrest by the decreased expression of cyclin D1, CDK2, and p-Rb, while TLR9 overexpression exerted the inverse effects. Furthermore, TLR9 overexpression could enhance the migration and invasion activities of the OS cells by the upregulation of matrix metalloproteinases 2 (MMP2) and MMP9, and the opposite result was observed in TLR9-silenced cells. Moreover, the nuclear factor kappa B (NF-κB) signaling pathway was activated by TLR9, and TLR9-induced malignant phenotype of OS cells was abrogated by the NF-κB antagonist BAY11-7082. Our study indicated that TLR9 might play a critical role in facilitating OS progression by activating the NF-κB signaling pathway, which may provide a valuable therapeutic target for OS.
Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , FN-kappa B , Receptor Toll-Like 9/genética , Osteosarcoma/genética , Transducción de Señal , Carcinogénesis , Neoplasias Óseas/genéticaRESUMEN
The current study aimed to evaluate the effects of chemokine stromal cell-derived factor (SDF)-1α and platelet-rich plasma (PRP) on bone formation and angiogenesis, and to assess whether SDF-1α and PRP could function synergistically. Four evenly distributed defects (8 mm in diameter) were generated in the calvarial bones of New Zealand white rabbits. All rabbits received four treatment regimens containing autogenous bone particles (AB), SDF-1α, or PRP. AB group presented significantly less bone formation compared with the other three groups 2 and 4 weeks after surgery. The amount of newly formed bone in the AB+PRP+SDF-1α group was similar to that in the AB + SDF-1α group at the 4-week time-point (p = 0.65), and was much greater than that in the AB and AB+PRP group (p < 0.001). Meanwhile, more new blood vessels were formed in the AB+PRP, AB+SDF-1α, and AB+PRP+SDF-1α group versus the AB group. AB+PRP+SDF-1α group showed statistically increased angiogenesis compared with the AB+PRP and AB+SDF-1α groups (both p < 0.05) after treatment for 2 and 4 weeks. These findings indicated that SDF-1α and PRP might exhibit synergistic effects to promote angiogenesis in early bone regeneration.
Asunto(s)
Regeneración Ósea/efectos de los fármacos , Quimiocina CXCL12/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Plasma Rico en Plaquetas/fisiología , Cráneo/efectos de los fármacos , Animales , Trasplante Óseo/métodos , Osteogénesis/efectos de los fármacos , Conejos , Cráneo/irrigación sanguínea , Cráneo/patología , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Surgical repair of bone defects remains challenging, and the search for alternative procedures is ongoing. Devices made of Mg for bone repair have received much attention owing to their good biocompatibility and mechanical properties. We developed a new type of scaffold made of a Mg-Zn-Ca alloy with a shape that mimics cortical bone and can be filled with morselized bone. We evaluated its durability and efficacy in a rabbit ulna-defect model. Three types of scaffold-surface coating were evaluated: group A, no coating; group B, a 10-µm microarc oxidation coating; group C, a hydrothermal duplex composite coating; and group D, an empty-defect control. X-ray and micro-computed tomography(micro-CT) images were acquired over 12 weeks to assess ulnar repair. A mechanical stress test indicated that bone repair within each group improved significantly over time (P < 0.01). The degradation behavior of the different scaffolds was assessed by micro-CT and quantified according to the amount of hydrogen gas generated; these measurements indicated that the group C scaffold better resisted corrosion than did the other scaffold types (P < 0.05). Calcein fluorescence and histology revealed that greater mineral densities and better bone responses were achieved for groups B and C than for group A, with group C providing the best response. In conclusion, our Mg-Zn-Ca-alloy scaffold effectively aided bone repair. The group C scaffold exhibited the best corrosion resistance and osteogenesis properties, making it a candidate scaffold for repair of bone defects.
Asunto(s)
Aleaciones/química , Calcio/química , Fracturas Óseas/patología , Magnesio/química , Andamios del Tejido , Zinc/química , Animales , Materiales Biocompatibles , Fenómenos Biomecánicos , Huesos/patología , Femenino , Fluoresceínas/química , Gases , Hidrógeno , Masculino , Minerales/química , Osteogénesis , Conejos , Reproducibilidad de los Resultados , Estrés Mecánico , Cúbito/diagnóstico por imagen , Microtomografía por Rayos X , Rayos XRESUMEN
In vitro evidence of hypoxia-induced resistance to cisplatin (CDDP)-mediated apoptosis exists in human osteosarcoma (OS). Gambogic acid (GA) is a promising chemotherapeutic compound that could increase the chemotherapeutic effectiveness of CDDP in human OS cells by inducing cell cycle arrest and promoting apoptosis. This study examined whether GA could overcome OS cell resistance to CDDP. Hypoxia significantly reduced levels of CDDP-induced apoptosis in the OS cell lines MG63 and HOS. However, combined treatment with GA and CDDP revealed a strong synergistic action between these drugs, and higher protein levels of the apoptosis-related factor Fas, cleaved caspase-8 and cleaved caspase-3 and lower expression of hypoxia-inducible factor (HIF)-1α are detected in both cell lines. Meanwhile, drug resistance was not reversed by exposure to the HIF-1α inhibitor 2-methoxyestradiol. These findings strongly suggest that hypoxia-induced resistance to CDDP is reversed by GA in OS cells independently of HIF-1α. Furthermore, in vivo studies using xenograft mouse models revealed that combination therapy with CDDP and GA exerted increased antitumor effects by inducing apoptosis. Taken together, our results demonstrate that GA may be a new potent therapeutic agent useful for targeting human OS cells.
Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Osteosarcoma , Xantonas/farmacología , Animales , Hipoxia de la Célula/efectos de los fármacos , Línea Celular Tumoral , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Proteínas de Neoplasias/metabolismo , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Osteosarcoma/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Matrine, a natural product, has been demonstrated to be a promising chemotherapeutic drug for some cancers. Using flow cytometric analysis of the cell cycle and apoptosis, we found that matrine inhibited the proliferation and induced apoptosis in the human osteosarcoma (OS) cell lines MG63, HOS, U2OS, and SAOS2 in vitro in a dose-dependent manner. We therefore assessed the role of the serine/threonine kinase Akt in the regulation of matrine-mediated cell growth inhibition and apoptosis induction in human OS cell lines. After treatment for 48 h, matrine induced G0/G1-stage cell cycle arrest in MG63, U2OS, and SAOS2 cells associated with an increase in the expression of p27(Kip1) and a decrease in the expression of Akt, glycogen synthase kinase 3 (GSK3)-ß (Ser9), and cyclin D1. Furthermore, the pro-apoptotic factor Bax was upregulated. Overall, our findings suggest that matrine may be an effective anti-osteosarcoma drug due to its ability to inhibit proliferation and induce apoptosis in OS cells, possibly through the involvement of Akt signaling.
Asunto(s)
Alcaloides/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Óseas/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinolizinas/farmacología , Transducción de Señal/efectos de los fármacos , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Osteosarcoma/metabolismo , Osteosarcoma/patología , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , MatrinasRESUMEN
We previously demonstrated that gambogic acid (GA) is a promising chemotherapeutic compound for human osteosarcoma treatment. The aim of this study was to detect whether the combination of lower-dose GA (0.3 mg/L) and cisplatin (CDDP) (1 mg/L) could perform a synergistic effect on inhibiting tumor in four osteosarcoma cell lines. Our results showed that the combination between GA at lower dose and CDDP significantly exerts a synergistic effect on inhibiting the cellular viability in MG63, HOS, and U2OS cells. In contrast, an antagonistic character was detected in SAOS2 cells exposed to the combined use of lower-dose GA (0.3 mg/L) and CDDP (1 mg/L). Then, analysis of cell cycle showed the combination of both drugs significantly induced the G2/M phase arrest, without any difference relative to GA treatment alone, in MG63 cells. Flow-cytometric analysis of cell apoptosis displayed that the apoptotic rate in the combination group is higher than that in GA treatment alone in MG63, HOS, and U2OS cells. The combined use of both drugs had no effect on mitochondrial membrane potential, but promoted the apoptosis-inducing function through triggering of CDDP in the three cell lines. By measurement of mitochondrial membrane potential, the activity of caspase-3 and the expressions of caspase-8 and caspase-9, it was showed that the apoptosis-promoting effect of the combined use of both drugs could be dependent on the death receptor apoptosis pathway, not dependent on the mitochondria apoptosis mechanism. This research, for the first time, demonstrates that GA could increase the chemotherapeutic effect of CDDP in human osteosarcoma treatment through inducing the cell cycle arrest and promoting cell apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Mitocondrias/metabolismo , Osteosarcoma/patología , Transducción de Señal/efectos de los fármacos , Xantonas/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Osteosarcoma/enzimologíaRESUMEN
OBJECTIVES: Keshin-Beck disease (KBD) is a particular type of osteoarthritis that affects many joints. However, the deformity of atlantoaxial joint has been rarely reported in KBD, and therefore its clinical and radiograph features have not been identified. METHODS: We reviewed data in 14 patients who were diagnosed with atlantoaxial dislocation (AAD) in KBD at our institution. The demographic data, clinical history, imaging data, operative data, and Japanese Orthopaedic Association score were collected for evaluation. RESULTS: The mean age at presentation was 50 ± 1.7 years old. The most common features of AAD in KBD were the osteoarthritis, characterized by hypertrophic dens and anterior arch of the atlas. The average inner anteroposterior diameter (IAPD) of C1 was 28 ± 3.5 mm and the average spinal canal diameter was 14 ± 3.3 mm, which were respectively lower than the control level. Five patients had severe C1 stenosis (IAPD < 26mm). Separated odontoid process, like os odontoideum, was seen 9 patients. The tip of dens fused to C1 was observed in 4 patients; 12 patients had high-riding vertebral artery; and 5 patients had severe C1 stenosis, and they underwent C1 laminectomy with C1-C2 interarticular fusion or occipital-cervical fusion. All the patients displayed neurologic improvement after surgery. CONCLUSIONS: The atlantoaxial level could be affected by KBD, which may lead to typical abnormalities and cause AAD. A C1 laminectomy with an C1-C2 interarticular fusion or occipital-cervical fusion is recommended for the patient with severe stenosis.
Asunto(s)
Articulación Atlantoaxoidea , Luxaciones Articulares , Enfermedad de Kashin-Beck , Osteoartritis , Enfermedades de la Columna Vertebral , Fusión Vertebral , Espondiloartropatías , Humanos , Persona de Mediana Edad , Constricción Patológica , Luxaciones Articulares/cirugía , Radiografía , Fusión Vertebral/métodos , Articulación Atlantoaxoidea/cirugíaRESUMEN
Magnesium based implants have the characteristics of bio-degradability, osteoconductive, and, regulatory strength. After the tissue has healed sufficiently, the burden of a second surgical procedure can be avoided. However, the degradation speed is so fast as to limit its clinical application. Hence, it is crucial for the biomedical magnesium alloys to be able to change their biodegradation behavior and speed. This paper reviews the degradability, biological activity and biocompatibility of magnesium and its alloys as orthopedic biomaterial in vitro and vivo to explore the possible way to modify the characteristics of its degradability, for the purpose of controllable degradation speed.
Asunto(s)
Implantes Absorbibles , Aleaciones/química , Materiales Biocompatibles/síntesis química , Placas Óseas , Magnesio/química , Animales , Tornillos Óseos , Sustitutos de Huesos/química , HumanosRESUMEN
Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) leads to significant morbidity. Other coadministered drugs may modulate the risk for BRONJ. The present study aimed to leverage bioinformatic data mining to identify drugs that potentially modulate the risk of BRONJ in cancer. Methods: A GEO gene expression dataset of peripheral blood mononuclear cells related to BRONJ in multiple myeloma patients was downloaded, and differentially expressed genes (DEGs) in patients with BRONJ versus those without BRONJ were identified. A protein-protein interaction network of the DEGs was constructed using experimentally validated interactions in the STRING database. Overrepresented Gene Ontology (GO) molecular function terms and KEGG pathways in the network were analysed. Network topology was determined, and 'hub genes' with degree ≥2 in the network were identified. Known drug targets of the hub genes were mined from the 'drug gene interaction database' (DGIdb) and labelled as candidate drugs affecting the risk of BRONJ. Results: 751 annotated DEGs (log FC ≥ 1.5, p < 0.05) were obtained from the microarray gene expression dataset GSE7116. A PPI network with 633 nodes and 168 edges was constructed. Data mining for drugs interacting with 49 gene nodes was performed. 37 drug interactions were found for 9 of the hub genes including TBP, TAF1, PPP2CA, PRPF31, CASP8, UQCRB, ACTR2, CFLAR, and FAS. Interactions were found for several established and novel anticancer chemotherapeutic, kinase inhibitor, caspase inhibitor, antiangiogenic, and immunomodulatory agents. Aspirin, metformin, atrovastatin, thrombin, androgen and antiandrogen drugs, progesterone, Vitamin D, and Ginsengoside 20(S)-Protopanaxadiol were also documented. Conclusions: A bioinformatic data mining strategy identified several anticancer, immunomodulator, and other candidate drugs that may affect the risk of BRONJ in cancer patients.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Metformina , Mieloma Múltiple , Antagonistas de Andrógenos , Andrógenos , Aspirina , Osteonecrosis de los Maxilares Asociada a Difosfonatos/genética , Caspasas , Biología Computacional , Minería de Datos , Humanos , Leucocitos Mononucleares , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Progesterona , Trombina , Vitamina DRESUMEN
BACKGROUND: The current study is aimed at identifying the cross-talk genes between periodontitis (PD) and rheumatoid arthritis (RA), as well as the potential relationship between cross-talk genes and pyroptosis-related genes. METHODS: Datasets for the PD (GSE106090, GSE10334, GSE16134) and RA (GSE55235, GSE55457, GSE77298, and GSE1919) were downloaded from the GEO database. After batch correction and normalization of datasets, differential expression analysis was performed to identify the differentially expressed genes (DEGs). The cross-talk genes linking PD and RA were obtained by overlapping the DEGs dysregulated in PD and DEGs dysregulated in RA. Genes involved in pyroptosis were summarized by reviewing literatures, and the correlation between pyroptosis genes and cross-talk genes was investigated by Pearson correlation coefficient. Furthermore, the weighted gene coexpression network analysis (WGCNA) was carried out to identify the significant modules which contained both cross-talk genes and pyroptosis genes in both PD data and RA data. Thus, the core cross-talk genes were identified from the significant modules. Receiver-operating characteristic (ROC) curve analysis was performed to identify the predictive accuracy of these core cross-talk genes in diagnosing PD and RA. Based on the core cross-talk genes, the experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. RESULTS: A total of 40 cross-talk genes were obtained. Most of the pyroptosis genes were not differentially expressed in disease and normal samples. By selecting the modules containing both cross-talk genes or pyroptosis genes, the blue module was identified to be significant module. Three genes, i.e., cross-talk genes (TIMP1, LGALS1) and pyroptosis gene-GPX4, existed in the blue module of PD network, while two genes (i.e., cross-talk gene-VOPP1 and pyroptosis gene-AIM2) existed in the blue module of RA network. ROC curve analysis showed that three genes (TIMP1, VOPP1, and AIM2) had better predictive accuracy in diagnosing disease compared with the other two genes (LGALS1 and GPX4). CONCLUSIONS: This study revealed shared mechanisms between RA and PD based on cross-talk and pyroptosis genes, supporting the relationship between the two diseases. Thereby, five modular genes (TIMP1, LGALS1, GPX4, VOPP1, and AIM2) could be of relevance and might serve as potential biomarkers. These findings are a basis for future research in the field.
Asunto(s)
Artritis Reumatoide/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/fisiología , Periodontitis/genética , Piroptosis/genética , HumanosRESUMEN
OBJECTIVE: To explore the possible way of proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) influencing diabetes mellitus-osteoarthritis (DM-OA) progression. METHODS: In vivo, eight-week-old male Sprague Dawley rats were induced with DM-OA by intraperitoneal injection of streptozotocin with high-fat diet feeding and intra-articular injection of monoiodoacetate. PSTPIP2 overexpression was achieved by intra-articular injection of lentivirus vectors. PSTPIP2 expression was verified by real-time polymerase chain reaction and Western blotting. Histological changes were examined by hematoxylin/eosin and safranin-O/fast-green staining. In vitro, rat synovial fibroblasts were induced DM-OA by stimulation of high glucose (HG) and interleukin (IL)-1ß. PSTPIP2 overexpression was achieved by lentivirus infection. U0126 was added as an ERK inhibitor. Levels of tumor necrosis factor (TNF)-α, IL-6, and IL-1ß were detected using enzyme-linked immunosorbent assay. Expression of matrix metalloproteinase (MMP)-3, MMP-13, aggrecanase-2 (ADAMTS-5), intercellular cell adhesion molecule (ICAM)-1, extracellular regulated protein kinase (ERK) and phospho-ERK (p-ERK) was detected by Western blotting. RESULTS: In DM-OA rats, PSTPIP2 relative messenger RNA (mRNA) level was significantly decreased compared to control rats. The protein expression was also decreased obviously. Inflammation score in synovium was dramatically increased, accompanying with increased TNF-α, IL-6, and IL-1ß levels. Osteoarthritis research society international (OARSI) score in cartilage was markedly increased, along with increased MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression. In PSTPIP2-overexpressed DM-OA rats, PSTPIP2 mRNA level and protein expression was increased compared to DM-OA rats received negative-control lentivirus vectors. The inflammation score, as well as TNF-α, IL-6, and IL-1ß levels were dramatically decreased. Also, the OARSI score and protein expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were decreased. In HG+IL-1ß-treated rat synovial fibroblasts, PSTPIP2 protein expression was decreased compared to normal glucose (NG)-treated cells. Levels of TNF-α, IL-6, and IL-1ß, as well as expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were increased. After cells were infected with PSTPIP2-overexpressed lentivirus, levels of TNF-α, IL-6, and IL-1ß, and expression of MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK were obviously decreased compared to cells infected with NC lentivirus. In addition, ERK inhibitor U0126 treatment also decreased the TNF-α, IL-6, and IL-1ßlevels and MMP-3, MMP-13, ADAMTS-5, ICAM-1, ERK and p-ERK expression in HG + IL-1ß treated rat synovial fibroblasts. CONCLUSION: Overexpression of PSTPIP2 alleviates synovial inflammation and cartilage injury during DM-OA progression via inhibiting ERK phosphorylation.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/farmacología , Cartílago Articular/efectos de los fármacos , Proteínas del Citoesqueleto/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Membrana Sinovial/efectos de los fármacos , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Inyecciones Intraarticulares , Ácido Yodoacético , Masculino , Osteoartritis de la Rodilla , Ratas , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
During osteoporosis, fat mass and obesity-associated protein (FTO) promotes the shift of bone marrow mesenchymal stem cells to adipocytes and represses osteoblast activity. However, the role and mechanisms of FTO on osteoclast formation and bone resorption remain unknown. In this study, we investigated the effect of FTO on RAW264.7 cells and bone marrow monocytes (BMMs)-derived osteoclasts in vitro and observed the influence of FTO on ovariectomized (OVX) mice model to mimic postmenopausal osteoporosis in vivo. Results found that FTO was up-regulated in BMMs from OVX mice. Double immunofluorescence assay showed co-localization of FTO with tartrate-resistant acid phosphatase (TRAP) in femurs of OVX mice. FTO overexpression enhanced TRAP-positive osteoclasts and F-actin ring formation in RAW264.7 cells upon RANKL stimulation. The expression of osteoclast differentiation-related genes, including nuclear factor of activated T cells c1 (NFATc1) and c-FOS, was upregulated in BMMs and RAW264.7 cells after FTO overexpression. FTO overexpression induced the phosphorylation and nuclear translocation of factor-kappa B (NF-κB) p65 in BMMs and RAW264.7 cells exposed to RANKL. ChIP and dual-luciferase assays revealed that FTO overexpression contributed to RANKL-induced binding of NF-κB to NFATc1 promoter. Rescue experiments suggested that FTO overexpression-mediated osteoclast differentiation was suppressed after intervention with a NF-κB inhibitor pyrrolidine dithiocarbamate. Further in vivo evidence revealed that FTO knockdown increased bone trabecula and bone mineral density, inhibited bone resorption and osteoclastogenesis in osteoporotic mice. Collectively, our research demonstrates that downregulated FTO inhibits bone resorption and osteoclastogenesis through NF-κB inactivation, which provides a novel reference for osteoporosis treatment.
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Resorción Ósea , FN-kappa B , Animales , Resorción Ósea/metabolismo , Diferenciación Celular , Ratones , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Obesidad/metabolismo , Osteoclastos/metabolismo , Osteogénesis , Ligando RANK/farmacologíaRESUMEN
Because of improving treatments and survival, 40% to 58% of patients with bone metastases from nonsmall cell lung cancer (NSCLC) will suffer from at least one skeletal-related event (SRE), affecting their quality of life, but the natural history of SRE is poorly understood. The study aimed to examine the factors involved in SRE-free survival (SRS) and overall survival (OS) of patients with NSCLC and bone metastases.This was a retrospective study of 211 patients with bone metastasis from NSCLC and treated at the Tumor Hospital Affiliated to Harbin Medical University between January 2007 and January 2012. OS and SRS were evaluated by the Kaplan-Meier method. The factors associated with SRS and OS were examined using multivariate Cox analyses.The 1 year OS was 55.9% and the median OS was 30 months (range, 1-98 months). Multivariate analyses showed that clinical staging at initial diagnosis (Pâ<â.001) and SRE (Pâ=â.033) were independently associated with OS, and clinical staging at initial diagnosis (Pâ=â.009), bone pain (Pâ=â.008), primary tumor radiotherapy (Pâ<â.001), and chemotherapy (Pâ=â.031) were independently associated with SRS. Stage I, II, and III patients under biphosphonate therapy fared better than those without biphosphonate treatment, but there was no difference for stage IV patients.The identification of factors associated with OS and SRS of patients with NSCLC and bone metastases should provide new clues for a better management of these patients.
Asunto(s)
Neoplasias Óseas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Fracturas Espontáneas/epidemiología , Hipercalcemia/epidemiología , Neoplasias Pulmonares/mortalidad , Compresión de la Médula Espinal/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/terapia , China/epidemiología , Femenino , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Degraded and osteogenic property of coated magnesium alloy was evaluated for the fracture fixation in rabbits. METHODS: Magnesium alloy AZ31 with a different coating thickness by microarc oxidation was used, and the bilateral radial fracture model was created by the bite bone clamp. Thirty-six New Zealand white rabbits in weight of 2.5~3.0 kg were randomly divided into A, B, and C groups at four time points and other 3 rabbits as the control group without magnesium alloy. Coated magnesium alloy AZ31 was implanted on the fracture and fixed with silk thread. Indexes such as general observation, histology, X-ray, hematology, and mechanical properties were observed and detected at 2nd, 4th, 8th, and 12th week after implantation. RESULTS: Fracture in each rabbit was healed at 12th week after implantation. Among the three groups, the best results of general observation, histology, and X-ray appeared in A group without coating. However, A group showed the worst results from the perspective of mechanical properties about tensile strength and flexural strength, which failed to reach that of the natural bone at the 12th week. Comprehensive results displayed that C group with 20-µm coating was better than others in mechanical properties, while there is no difference between B and C groups in hematology. CONCLUSIONS: Degradation rate is inversely proportional to the coating thickness. And magnesium alloy with a 20-µm coating is more suitable for the fracture fixation.
Asunto(s)
Aleaciones/farmacología , Fijación Interna de Fracturas/instrumentación , Dispositivos de Fijación Ortopédica , Osteogénesis/efectos de los fármacos , Fracturas del Radio/cirugía , Animales , Materiales Biocompatibles Revestidos , Femenino , Curación de Fractura , Magnesio/sangre , Masculino , Ensayo de Materiales/métodos , Diseño de Prótesis , Conejos , Resistencia a la TracciónRESUMEN
Sesamin, a bioactive component extracted from sesame, has been reported to exert anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti-inflammatory effects of sesamin on IL-1ß-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that sesamin treatment significantly inhibited PGE2 and NO production induced by IL-1ß. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1ß-stimulated chondrocytes. Sesamin also inhibited IL-1ß-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, sesamin was found to up-regulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of sesamin. In conclusion, our results suggested that sesamin showed anti-inflammatory effects in IL-1ß-stimulated chondrocytes by activating Nrf2 signaling pathway.
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Antiinflamatorios/farmacología , Condrocitos/efectos de los fármacos , Dioxoles/farmacología , Interleucina-1beta/farmacología , Lignanos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Osteoartritis de la Rodilla/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Condrocitos/inmunología , Condrocitos/metabolismo , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Hemo-Oxigenasa 1/metabolismo , Humanos , Metaloproteinasas de la Matriz Secretadas/metabolismo , Persona de Mediana Edad , Factor 2 Relacionado con NF-E2/genética , Inhibidor NF-kappaB alfa/metabolismo , Óxido Nítrico/metabolismo , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/inmunología , Osteoartritis de la Rodilla/metabolismo , Fosforilación , Interferencia de ARN , Factor de Transcripción ReIA/metabolismo , TransfecciónRESUMEN
One of the keys to allowing Mg alloys to serve as biodegradable materials is how to balance their degradation behaviours and mechanical properties in physiological environment. In this study, a novel Mg-6Ho-0.5Zn alloy (wt%) containing profuse basal plane stacking faults (SFs) is prepared. This newly-developed alloy with SFs exhibiting uniform corrosion behaviour, low corrosion rate and high mechanical properties, as compared to the classic Mg-Ho based alloys (Mg-6Ho and Mg-6Ho-1.5Zn). Furthermore, the Mg-6Ho-0.5Zn alloy shows no significant toxicity to Saos-2 cells. An original uniform corrosion mechanism is proposed by combining the special defect structure, orientation of SFs and promptly effective corrosion film. The development of the new microstructure for Mg-Ho based alloys with desirable corrosion performance has important implications in developing novel degradable Mg-based implant materials.
RESUMEN
Designing the new microstructure is an effective way to accelerate the biomedical application of magnesium (Mg) alloys. In this study, a novel Mg-8Er-1Zn alloy with profuse nano-spaced basal plane stacking faults (SFs) was prepared by combined processes of direct-chill semi-continuous casting, heat-treatment and hot-extrusion. The formation of SFs made the alloy possess outstanding comprehensive performance as the biodegradable implant material. The ultimate tensile strength (UTS: 318 MPa), tensile yield strength (TYS: 207 MPa) and elongation (21%) of the alloy with SFs were superior to those of most reported degradable Mg-based alloys. This new alloy showed acceptable biotoxicity and degradation rate (0.34 mm/year), and the latter could be further slowed down through optimizing the microstructure. Most amazing of all, the uniquely uniform in vitro/vivo corrosion behavior was obtained due to the formation of SFs. Accordingly we proposed an original corrosion mechanism for the novel Mg alloy with SFs. The present study opens a new horizon for developing new Mg-based biomaterials with highly desirable performances.
Asunto(s)
Materiales Biocompatibles/química , Magnesio/química , Aleaciones/química , Animales , Corrosión , Ensayo de Materiales , Fenómenos Mecánicos , Zinc/químicaRESUMEN
Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30min after the SCI was successfully induced, the animals were intraperitoneally given 40mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin-eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin - 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.
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Curcumina/uso terapéutico , Edema/tratamiento farmacológico , Edema/metabolismo , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismo , Animales , Acuaporina 4/metabolismo , Modelos Animales de Enfermedad , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
Ample cell adhesion to scaffolds is essential for effective bone tissue engineering. Chitosan/hydroxyapatite (CS/HA) scaffolds with channel-shaped and spherically shaped pore morphologies were prepared via in situ compositing hybridization in combination with lyophilization. The sizes of channel-shaped and spherically shaped pores of the CS/HA scaffolds were 150-650 µm and 3-15 µm, respectively. The RGD peptide (Arg-Gly-Asp) was bound to the surface of CS/HA scaffolds via physical adsorption. More than 63% of RGD present in a PBS solution spontaneously adsorbed onto CS/HA scaffolds. High numbers of viable bone marrow stromal cells (BMSCs) were observed by confocal and fluorescence microscopy for cells cultured on CS/HA scaffolds with and without RGD for 3 days. BMSCs on CS/HA scaffolds with RGD (RGD-CS/HA) were incubated for 4 h under standard culture conditions, and the degree of cell adhesion was calculated. Cell adhesion to RGD-CS/HA scaffolds with different RGD concentrations was 71.6% and 80.7%, respectively. This was 30.9% and 47.5% higher than adhesion to the CS/HA scaffold without RGD, respectively. BMSCs cultured on the scaffolds for 14 days with osteogenic supplements expressed 103% higher alkaline phosphatase on the RGD-CS/HA scaffold (0.001 97 ± 0.000 31 U/L/ng), than on the unmodified scaffold (0.000 97 ± 0.000 25 U/L/ng) (p < 0.01), indicating that a RGD peptide significantly promotes osteogenic differentiation of BMSCs on CS/HA scaffolds. The results of this study indicate that RGD-CS/HA scaffolds promote initial cell adhesion, spread and differentiation toward an osteogenic phenotype.
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Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Oligopéptidos/farmacología , Osteoblastos/citología , Osteoblastos/fisiología , Osteogénesis/fisiología , Andamios del Tejido , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Células Cultivadas , Células Inmovilizadas/efectos de los fármacos , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/farmacología , Diseño de Equipo , Análisis de Falla de Equipo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Oligopéptidos/química , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Unión Proteica , Ratas , Ratas Endogámicas F344 , Células del Estroma/citología , Células del Estroma/efectos de los fármacos , Células del Estroma/fisiologíaRESUMEN
Based on the theories of mass-transfer and two-double integrated staged multi-phase anaerobe (TSMPA), a pilot-scale opposite folded plate hybrid anaerobic reactor (OFPHAR) was designed to treat low concentration sewage. All the trial lasted 12 months and the results indicated that the optimal HRT was 6h. At this HRT, the COD, TP and TN removal rate were 78.58%, 35.15%, 39.17%, respectively, at 25 degrees C +/- 2 degrees C. The optimal rate of anaerobic section was 45%-65%. Controlled HRT = 6 h, the COD, TP and TN removal rate were 64.37%, 20.72%, 23.65%, respectively, and the specific methane production capacity were 1.85 mL/(g x h) when the temperature decreased to 7 degrees C. The results of trial indicated that apply this OFPHAR to treat low concentration sewage at low temperature in north China is feasible.