A novel nanofibrous composite scaffold composed of super-paramagnetic γ-Fe2O3 nanoparticles (MNP), hydroxyapatite nanoparticles (nHA) and poly lactide acid (PLA) was prepared using electrospinning technique. The scaffold well responds extern static magnetic field with typical saturation magnetization value of 0.049 emu/g as well as possesses nanofibrous architecture. The scaffolds were implanted in white rabbit model of lumbar transverse defects. Permanent magnets are fixed in the rabbit cages to provide static magnetic field for the rabbits post surgery. Results show that MNP incorporated in the nanofibers endows the scaffolds super-paramagnetic responsive under the applied static magnetic field, which accelerates new bone tissue formation and remodeling in the rabbit defect. The scaffold also exhibits good compatibility of CK, Cr, ALT and ALP within normal limits in the serum within 110 days post implantation. In conclusion, the super-paramagnetic responding scaffold with applying of external magnetic field provides a novel strategy for scaffold-guided bone repair.
BackgroundOvarian cancer (OCa) peritoneal metastasis is the leading cause of cancer–related deaths in women with limited therapeutic options available for treating it and poor prognosis, as the underlying mechanism is not fully understood.MethodThe clinicopathological correlation of G9a expression was assessed in tumor specimens of ovarian cancer patients. Knockdown or overexpression of G9a in ovarian cancer cell lines was analysed with regard to its effect on adhesion, migration, invasion and anoikis-resistance. In vivo biological functions of G9a were tested by i.p. xenograft ovarian cancer models. Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream target genes.ResultsWe found that the expression of histone methyltransferase G9a was highly correlated with late stage, high grade, and serous-type OCa. Higher G9a expression predicted a shorter survival in ovarian cancer patients. Furthermore, G9a expression was higher in metastatic lesions compared with their corresponding ovarian primary tumors. Knockdown of G9a expression suppressed prometastatic cellular activities including adhesion, migration, invasion and anoikis-resistance of ovarian cancer cell lines, while G9a over-expression promoted these cellular properties. G9a depletion significantly attenuated the development of ascites and tumor nodules in a peritoneal dissemination model. Importantly, microarray and quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer. Expression of these genes was also inversely correlated with G9a expression in OCa specimens.ConclusionWe propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-189) contains supplementary material, which is available to authorized users.
In this work, a paramagnetic nanofibrous composite film was fabricated with poly lactide, hydroxyapatite and γ-Fe(2)0(3) nanoparticles using the electrospinning technique. The composite film significantly enhanced the proliferation, differentiation and ECM secretion of the osteoblast cells under a static magnetic field, which offers promising application potentials in bone tissue engineering and bone regeneration therapy.
BACKGROUND: Annexin A1 (AnxA1) has been well-known as a glucocorticoid-regulated anti-inflammatory protein, and it is implicated in tumorigenesis in a tumor type-specific pattern. However, the role of AnxA1 in gastric cancer (GC) is indeterminate, and the underlying mechanism is not clear. The purpose of this study was to evaluate the prognostic significance and associated mechanism of AnxA1 in GC. METHODS: Immunohistochemical staining was employed to analyze 118 GC patients. Both AnxA1 gain-of-function and loss-of-function approaches were performed in GC cells. Western blotting and reverse-transcription polymerase chain reaction were used for assessment of the AnxA1 regulation mechanism in GC cells. An intraperitoneal inoculation model in severe combined immunodeficient mice was used for an in vivo assay. RESULTS: High AnxA1 expression was significantly associated with peritoneal metastasis (P ¼ .009) and serosal invasion (P ¼ .044). Cox multivariate analysis showed that high AnxA1 expression was an independent risk factor for poor overall survival in GC patients (P ¼ .037). AnxA1 expression positively correlated with invasiveness of human GC cells both in vitro and in vivo. AnxA1 could regulate the GC cell invasion through the formyl peptide receptor (FPR)/extracellular signalregulated kinase/integrin beta-1-binding protein pathway, and all 3 FPRs (FPR1 through FPR3) were involved in the regulation process. CONCLUSIONS: High AnxA1 expression was associated with more serosal invasion, more peritoneal metastasis, and poorer overall survival in GC patients. The current study demonstrated a novel mechanism involving FPRs, extracellular signal-regulated kinases 1
The biomedical applications of carbon nanotubes (CNTs) have attracted deep interest in recent years. Antitumor immunotherapy has the potential to improve the prognosis of cancer treatment but the efficacy of current immunotherapy generally needs further improvement. Multi-walled CNTs conjugated to tumor lysate protein are investigated as to whether they would enhance the efficacy of an immunotherapy employing a tumor-cell vaccine in a mouse model bearing the H22 liver cancer. The tumor cure rate is found to be markedly improved by CNTs conjugated to tumor lysate protein. The cellular antitumor immune reaction is also enhanced. Moreover, the observed antitumor immune response is relatively specific against the tumor intended for treatment. These findings suggest that CNTs may have a prospective role in the development of new antitumor immunotherapies.
Blood compatibility has been an occlusion for biomaterials used in the cardiovascular system. In this work, a multiwalled carbon nanotubes-polyurethane composite (MWNT-PU) was prepared through a controlled co-precipitation. The surface chemical composition of treated carbon nanotubes was analyzed with XPS and the thermal behaviors of composite were characterized by DSC. The platelet adhesion and activation caused by the composite were evaluated by using SEM and flow cytometric analysis, respectively, and the disruption of red blood cells was analyzed through measuring the absorbance of free hemoglobin. The experimental results demonstrated that: (1) Multiwalled carbon nanotubes (MWNTs) with oxygen-containing functional groups could be well dispersed in polyurethane matrix through a controlled coprecipitation; (2) the composite surface displayed a significantly improved anticoagulant function, which can be indicative of the promising potentials of carbon nanotube-based materials in the implants and medical devices applied in blood-contacting environments.
Melatonin plays important roles in various aspects of biological processes. However, it is less known on the effects and mechanism of melatonin on the postharvest physiological deterioration (PPD) process of cassava, which largely restricts the potential of cassava as a food and industrial crop. In this study, we found that exogenous application of melatonin significantly delayed PPD of cassava tuberous roots by reducing H2O2 content and improving activities of catalase and peroxidase. Moreover, 3425 differentially expressed genes by melatonin during the PPD process were identified by transcriptomic analysis. Several pathways were markedly affected by melatonin treatments, including metabolic-, ion homeostasis-, and enzyme activity-related processes. Further detailed analysis revealed that melatonin acted through activation of ROS-scavenging and ROS signal transduction pathways, including antioxidant enzymes, calcium signaling, MAPK cascades, and transcription factors at early stages. Notably, the starch degradation pathway was also activated at early stages, whereas it was repressed by melatonin at middle and late stages, thereby indicating its regulatory role in starch metabolism during PPD. Taken together, this study yields new insights into the effect and underlying mechanism of melatonin on the delay of PPD and provides a good strategy for extending shelf life and improvement of cassava tuberous roots.
Carbon nanotubes have attracted intensive interests in biomedical research in recent years. In this study, a novel type of carbon nanotubes material so called nonwoven single-walled carbon nanotubes (SWNTs) with nanotopographic structure and macroscopic volume was used as cell growing scaffold. The morphology and surface chemistry of nonwoven SWNTs were observed and characterized through scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. The cells were cultivated in nonwoven SWNTs and in other types of substrate as control. The cells growth behaviors including adhesion, proliferation, and cytoskeletal development was investigated by using cell viability assay and confocal observation. The experimental results indicated that nonwoven SWNTs exhibited significant enhancement to the cells adhesion and proliferation in at least 3 weeks. Numerous and highly organized cytoskeletal structures were observed when the cells were cultured in nonwoven SWNTs. Furthermore, an obvious promotional influence of the cells cultivated in nonwoven SWNTs scaffold upon the proliferation of those growing in the other kind of substrate through cell-cell communication had been found. The results obtained in this work are of significance to in vitro cell amplification in large scale, tissue regeneration, or guided repair, as well as biomedical device application.
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