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OBJECTIVES: S100-ß has been identified as a sensitive biomarker in central nervous system injuries. However, the functions and mechanisms of S100-ß are unknown in spinal cord injury. METHODS: Spinal cord injury (SCI) mouse model was generated by surgical operation, microglia activation model was established by inducing BV-2 cells with LPS. The SCI model was evaluated by Basso-Beattie-Bresnahan (BBB) behavioral score, HE staining, and Nissl staining. The expression level of S100-ß was detected by qRT-PCR, western blot, and immunofluorescence. qRT-PCR and western blot were used to detect the expression of iNOS and CD16. Pro-inflammatory cytokines TNF-α and IL-1ß levels were detected by qRT-PCR and ELISA. RESULTS: The expression of IL-1ß, TNF-α, iNOS, and CD16 increased at 3rd day after SCI. In BV2 microglia, LPS treatment promoted the expression of S100-ß, IL-1ß, TNF-α, iNOS, and CD16. Knockdown of S100-ß reduced the expression of iNOS stimulated by LPS. Over-expression of S100-ß increased IL-1ß and TNF-α, and S100-ß inhibition suppressed IL-1ß and TNF-α. In SCI mice, knockdown of S100-ß attenuated the spinal cord injury and inhibited the expression of iNOS, IL-1ß, and TNF-α. CONCLUSIONS: Down-regulation of S100-ß could inhibit the pathogenesis of SCI and inhibit the activation of M1 macrophages. S100-ß may be a useful diagnostic biomarker or therapeutic target for SCI.
Assuntos
Traumatismos da Medula Espinal , Animais , Macrófagos , Camundongos , Microglia , Fenótipo , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
The study was aimed at deciphering the function and mechanism of circ_0081001 in osteosarcoma (OS). In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for quantifying circ_0081001, miR-494-3p, and BTB domain and CNC homolog 1 (BACH1) mRNA expressions in OS tissues and cells. Cell counting kit-8 (CCK-8) assay, together with 5-Ethynyl-2'-deoxyuridine (EdU) assay, was performed for evaluating cell proliferation; the alterations in apoptosis were analyzed utilizing flow cytometry; Transwell assay was conducted for examining cell migration and invasion; moreover, Western blot was utilized for the quantification of BACH1 protein expression; bioinformatics, dual-luciferase reporter gene, and RNA-binding protein immunoprecipitation assays were executed for validating the binding relationships between circ_0081001 and miR-494-3p, and between miR-494-3p and BACH1. As shown, circ_0081001, whose expression was elevated in OS tissues, had a negative association with miR-494-3p expression and a positive correlation with BACH1 expression. After circ_0081001 was overexpressed, the proliferation, migration, and invasion of OS cells were boosted but the apoptosis was reduced, whereas miR-494-3p exhibited opposite effects. The binding sites between circ_0081001 and miR-494-3p, and between miR-494-3p and the 3'UTR of BACH1 were experimentally verified. In conclusion, circ_0081001/miR-494-3p/BACH1 axis promoted the malignant biological behaviors of OS cells.
Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Osteossarcoma/genética , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Idoso , Apoptose , Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Biologia Computacional , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Osteosarcoma (OS) is one of the most common primary bone tumors in children and adolescents. However, the molecular mechanism of OS tumorigenesis is still little known. Circular RNA (circRNA) is a key player in the progression of many cancers. This study is performed to decipher the role and mechanism of circ_0008259 in the progression of OS. METHODS: A differentially expressed circRNA, circ_0008259, was screened out by analyzing the expression profile of circRNA in OS tissue. Circ_0008259, miR-21-5p and programmable cell death 4 (PDCD4) mRNA expression levels in OS tissues and cells were detected by qRT-PCR. Cell viability, metastatic potential and apoptosis were evaluated by cell counting kit-8 assay, Transwell and flow cytometry. The targeting relationship between circ_0008259 and miR-21-5p, and miR-21-5p and PDCD4 mRNA was analyzed and probed by bioinformatics analysis and dual-luciferase reporter assay, RNA-binding protein immunoprecipitation assay and RNA-pull down assay. The regulatory effects of circ_0008259 and miR-21-5p on PDCD4 protein expression in OS cells were detected by Western blot assay. RESULTS: Circ_0008259 expression and PDCD4 expression were down-regulated and miR-21-5p expression was elevated in the OS tissues and cells. Functional experiments showed that circ_0008259 overexpression significantly inhibited the proliferation and metastatic potential of OS cells and promoted the apoptosis. Besides, PDCD4 was validated as the target gene of miR-21-5p, and circ_0008259 could competitively bind to miR-21-5p, thus up-regulating PDCD4 expression in OS cells. CONCLUSIONS: Circ_0008259 suppresses OS progression via regulating miR-21-5p/PDCD4 axis.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Ósseas/patologia , MicroRNAs/metabolismo , Osteossarcoma/patologia , RNA Circular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Humanos , Osteossarcoma/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
By combining two n-type groups, pyridine and oxadiazole, with one p-type carbazole group, two novel bipolar hosts, namely 2-(3-(9H-carbazol-9-yl)-[1,1'-biphenyl]-3-yl)-5-(pyridin-2-yl)-1,3,4-oxadiazole (PyOxd-mCz) and 2-(4'-(9H-carbazol-9-yl)-[1,1'-biphenyl]-3-yl)-5-(pyridin-2-yl)-1,3,4-oxadiazole (PyOxd-pCz) have been developed as hosts for blue and green phosphorescent organic light-emitting diodes (PhOLEDs). The two compounds exhibit similar HOMO levels of -5.64 eV for PyOxd-mCz and -5.63 eV for PyOxd-pCz and the same LUMO level of -2.60 eV. With a more twisted configuration due to meta connections, PyOxd-mCz possesses a higher triplet energy level (E T = 2.77 eV) and more balanced carrier transport than PyOxd-pCz (E T = 2.60 eV). PyOxd-mCz hosted devices achieve a peak current efficiency of 39.7 cd A-1 and a maximum EQE of 20.8% with a low turn-on voltage of 3.5 V for FIrpic and 55.2 cd A-1 and 16.4% for Ir(ppy)3. Apart from the appropriate frontier molecular orbital levels and sufficiently high triplet energy of PyOxd-mCz, the more balanced carrier transport plays a key role for excellent device performance.
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Osteosarcoma (OS) is one of the most common malignant tumors derived from mesenchymal tissue and is highly invasive, mainly in children and adolescents. Treatment of OS is mostly based on standard treatment options, including aggressive surgical resection, systemic chemotherapy, and targeted radiation therapy, but the 5-year survival rate is still low. MicroRNA (miRNA) is a highly conserved type of endogenous nonprotein-encoding RNA, about 19-25 nucleotides in length, whose transcription process is independent of other genes. Generally, miRNAs play a role in regulating cell proliferation, differentiation, apoptosis, and development by binding to the 3' untranslated region of target mRNAs, whereby they can degrade or induce translational silencing. Although miRNAs play a regulatory role in various metabolic processes, they are not translated into proteins. Several studies have shown that miRNAs play an important role in the diagnosis, treatment, and prognosis of OS. Herein, the authors describe new advances in the diagnosis, prognosis, and treatment of miRNAs in OS.