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Objective To screen the potential key genes of osteosarcoma by bioinformatics methods and analyze their immune infiltration patterns. Methods The gene expression profiles GSE16088 and GSE12865 associated with osteosarcoma were obtained from the Gene Expression Omnibus(GEO),and the differentially expressed genes(DEGs)related to osteosarcoma were screened by bioinformatics tools.Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and analysis of immune cell infiltration were then carried out for the DEGs.The potential Hub genes of osteosarcoma were identified by protein-protein interaction network,and the expression of Hub genes in osteosarcoma and normal tissue samples was verified via the Cancer Genome Atlas(TCGA). Results A total of 108 DEGs were screened out.GO annotation and KEGG pathway enrichment revealed that the DEGs were mainly involved in integrin binding,extracellular matrix (ECM) structural components,ECM receptor interactions,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Macrophages were the predominant infiltrating immune cells in osteosarcoma.Secreted phosphoprotein 1(SPP1),matrix metallopeptidase 2(MMP2),lysyl oxidase(LOX),collagen type V alpha(II)chain(COL5A2),and melanoma cell adhesion molecule(MCAM)presented differential expression between osteosarcoma and normal tissue samples(all P<0.05). Conclusions SPP1,MMP2,LOX,COL5A2,and MCAM are all up-regulated in osteosarcoma,which may serve as potential biomarkers of osteosarcoma.Macrophages are the key infiltrating immune cells in osteosarcoma,which may provide new perspectives for the treatment of osteosarcoma.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Macrófagos Associados a Tumor , Neoplasias Ósseas/genética , Neoplasias Ósseas/imunologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Osteossarcoma/genética , Osteossarcoma/imunologia , Fosfatidilinositol 3-Quinases/genética , Macrófagos Associados a Tumor/imunologiaRESUMO
OBJECTIVE: The present retrospective study evaluated the clinical results of full-endoscopic lumbar discectomy (FELD) for the treatment of lumbar disc herniation (LDH) with lumbar posterior ring apophysis fracture (PRAF) using an interlaminar or a transforaminal approach at an inpatient surgery center. METHODS: Patients with single-level LDH with type III PRAF who had undergone FELD using an interlaminar or a transforaminal approach from January 2010 to December 2015 were enrolled. The general data recorded included sex, age, location, surgical approach, operative time, hospital stay, perioperative complications, and recurrence. The presence of mobile and immobile fragments was documented. The clinical outcomes were evaluated using a visual analog scale for low back and leg pain. The Oswestry Disability Index was used for the functional assessment and the modified MacNab criteria for patient satisfaction. RESULTS: FELD was performed successfully in all cases and no serious perioperative complications were observed. A mobile fragment of PRAS was present in 18 patients and an immobile fragment in 15 patients. Complications occurred in 2 of the 33 included patients; 1 dual tear (3.0%) and 1 transient dysesthesia (3.0%) that did not require further treatment. Recurrence developed in 1 patient (3.0%) and required reoperation. The visual analog scale and Oswestry Disability Index scores had significantly improved postoperatively at 3, 6, and 12 months and the final follow-up visit (P < 0.05). Using the modified MacNab criteria, an excellent or good rate of 93.4% was achieved. CONCLUSIONS: FELD is a safe and effective minimally invasive approach for the treatment of LDH with type III PRAF. Sufficient preparation and experience are required to achieve satisfactory results.
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BACKGROUND: Cardiotrophin-1 (CT-1), a member of the IL-6 superfamily, is elevated in the serum of patients with ischemic and valvular heart disease. In this study, we hypothesized that CT-1 induces endothelial cell angiogenesis and that the ADMA/DDAH pathway plays an important role in the process. METHODS: pEGFP-N1-CTF1-GFP and pEGFP-N1 were constructed and used to transiently transfect to HUVECs, mediated by LipofectamineTM 2000. After transfection, the expression of CT-1 was examined by qRT-PCR and western blotting. Endothelial cell proliferation assay was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) method. Migration assay was performed using transwell, tube formation test was examined on Matrigel, eNOSmRNA expression was assayed by qRT-PCR, DDAH I, DDAHII and VEGF expression were detected by western blotting, the level of ADMA and the activity of DDAH were measured by High Performance Liquid Chromatography, NOS activity and the concentration of NO were assayed by L-[3H] citrulline production from L-[3H]arginine. RESULTS: Overexpression of CT-1, increased endothelial cell proliferation, migration and formation of blood vessels, upregulated the expression of eNOSmRNA, DDAHI, DDAHII and VEGF, elevated the activity of DDAH and NOS, decreased the level of ADMA and promoted NO synthesis. In contrast, ADMA partially inhibited the effects of CT-1 induction. CONCLUSIONS: Overexpression of CT-1 increases cell proliferation, migration and formation of blood vessels. This result also suggests that CT-1 may regulate angiogenesis through the ADMA/DDAH pathway.
Assuntos
Amidoidrolases/metabolismo , Arginina/análogos & derivados , Citocinas/fisiologia , Neovascularização Fisiológica/fisiologia , Arginina/metabolismo , Ensaios de Migração Celular , Movimento Celular/fisiologia , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Endotélio Vascular/citologia , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia , Tetraspanina 24/metabolismo , Transfecção , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
We previously reported that CD151 promotes neovascularization and improves blood perfusion in rat hind-limb ischemia model, but the precise mechanism is still unclear. Endothelial cell proliferation and cell migration play critical roles in angiogenesis. Many growth factors and hormones have been shown to regulate cell proliferation, cell migration and angiogenesis, including the activation of eNOS activity, via the PI3K/Akt signaling pathway. Whether CD151 induces cell proliferation and cell migration via PI3K/Akt signaling pathway is not known. Here we showed that CD151 promotes human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation in vitro, accompanied by increased phosphorylation of Akt and eNOS, leading to increased eNOS activity and nitric oxide (NO) levels after rAAV-CD151 infection, whereas infection with rAAV-anti-CD151 attenuated the effects of CD151, which suggested that CD151 can activate PI3K/Akt pathway. Moreover, inhibitors of PI3K (LY294002) and eNOS (l-NAME) can attenuate CD151-induced cell proliferation and cell migration. The results suggested that activation of PI3K/Akt signaling pathway mediates CD151-induced cell proliferation and migration.