Tubastatin alleviates epidural fibrosis via negatively targeting TGFß/PI3K/Akt pathway.

Epidural fibrosis (EF) is a chronic, progressive and severe disease. Histone deacetylase 6 (HDAC6) regulates biological signals and cell activities by deacetylating lysine residues and participates in TGF-ß-induced epithelial-mesenchymal transition (EMT). Nevertheless, the effect and mechanism of HDAC6 in EF remain unclear. To investigate the effect and mechanism of HDAC6 inhibition on repressing epidural fibrosis. HDAC6 expression and α-smooth muscle actin (α-SMA) in normal human tissue and human EF tissue were assessed by quantitative real-time PCR (qRT-PCR) and western blotting. Human fibroblasts were treated with TGF-ß ± HDAC6 inhibitors (Tubastatin) and fibrotic markers including collagen I, collagen III, α-SMA and fibronectin were assessed using western blotting. Then TGFß1 receptor (TGFß1-R), PI3K and Akt were analyzed using qRT-PCR and western blotting. Rats were undergone laminectomy± Tubastatin (intraperitoneally injection; daily for 7 days) and epidural scar extracellular matrix (ECM) expression was gauged using immunoblots. Increasing HDAC6 expression was associated with α-SMA enrichment. Tubastatin remarkably restrained TGF-ß-induced level of collagen and ECM deposition in human fibroblasts, and the discovery was accompanied by decreased PI3K and Akt phosphorylation. Moreover, Tubastatin also inhibited TGF-ß-mediated HIF-1α and VEGF expression. In the epidural fibrosis model, we found that Tubastatin weakened scar hyperplasia and collagen deposition, and effectively inhibited the process of epidural fibrosis. These results indicated that Tubastatin inhibited HDAC6 expression and decreased TGF-ß/ PI3K/ Akt pathway that promotes collagen and ECM deposition and VEGF release, leading reduction of myofibroblast activation. Hence, Tubastatin ameliorated epidural fibrosis development.

Treatment of tibial traumatic osteomyelitis with negative pressure closure drainage combined with open bone grafting or bone migration and its effect on the levels of CRP, TNF-α and IL-6 in the serum.

Objective: To observe the effect of negative pressure closure drainage combined with open bone grafting or bone migration in the treatment of tibial traumatic osteomyelitis. Methods: Eighty-six (86) cases of tibial traumatic osteomyelitis admitted to Hospital of the Chinese people's Liberation Army from September 2017 to September 2018 were randomly divided into control group and observation group, forty-three (43) cases each. Debridement, open bone grafting or bone migration was given to the control group.The observation group was treated with negative pressure closed drainage on the basis of the control group. In addition, the serum components such as CRP, TNF-α, IL-6 of the control group and observation group were detected respectively after surgery. Results: Observation group granulation cover wound, fracture healing time was shorter than the control group, fracture healing rate was better than the control group, the difference has statistical significance (P<0.05). By comparing serum CRP, TNF-α, IL-6 levels before and after treatment in the two groups, it was found that the observation group was lower than the control group (P<0.05, respectively). Serum CRP, TNF-α, IL-6 levels were significantly (P<0.05). Conclusion: The treatment of tibial traumatic osteomyelitis with negative pressure closure drainage combined with open bone grafting or bone displacement has a good effect on fracture healing and is worth popularizing.

TFAP2C-mediated LINC00922 signaling underpins doxorubicin-resistant osteosarcoma.

Long noncoding RNAs (lncRNAs) have been indicated as critical regulators in osteosarcoma (OS). However, the function of lncRNAs in doxorubicin (DXR)-resistant OS remain unclear. Here, present study investigated the functions of lncRNA LINC00922 on the DXR resistance in OS tumorigenesis. LncRNA expression profile was detected using lncRNA microarray in DXR-resistant OS cells (MG63/DXR) and parental cells (MG63). Molecular binding was detected using luciferase reporter assay and chromatin immunoprecipitation. DXR sensitivity assay was detected using CCK-8 assay. Results showed that LINC00922 was significantly up-regulated in OS tissue specimens. Cellular assays showed that LINC00922 increased DXR IC50 and the knockdown of LINC00922 repressed the tumor growth of OS cells. Mechanistic assays showed that LINC00922 acts as a sponge of miR-424-5p, and miR-424-5p targeted the 3'-untranslated region of transcription factor activating protein 2 gamma (TFAP2C) mRNA. Moreover, TFAP2C promoted transcription of LINC00922 in a positive feedback loop comprising TFAP2C, LINC00922, and miR-424-5p. Collectively, these findings uncovered the function of TFAP2C/LINC00922/miR-424-5p feedback loop in DXR resistance, suggesting new therapeutic direction for OS.

Long noncoding RNA LINC00858 promotes osteosarcoma through regulating miR-139-CDK14 axis.

Long noncoding RNAs (lncRNAs) have been identified to modulate the tumorigenesis of human cancers. The in-depth of lncRNAs on human osteosarcoma oncogenesis is still ambiguous. In present study, functional and mechanism experiments were conducted to investigate the role of long intergenic non-protein coding RNA 00858 (LINC00858) on human osteosarcoma tumorigenesis. Results demonstrated that LINC00858 expression was significantly upregulated in both osteosarcoma tissues and cell lines. Mechanism assays presented that LINC00858 silencing significantly repressed osteosarcoma cells' proliferation and invasion in vitro, and inhibited the tumor growth in vivo. In further experiments, LINC00858 was identified to sponge miR-139 to form RNA-induced silencing complex (RISC) using luciferase reporter assay and RNA immunoprecipitation (RIP). Besides, CDK14 was validated to be the target protein the miR-139. Rescue experiments confirmed the role of LINC00858/miR-139/CDK14 pathway on osteosarcoma cells' phenotype. In summary, these data prove that LINC00858/miR-139/CDK14 axis promotes the tumorigenesis of osteosarcoma, providing a new mechanism or target for osteosarcoma.

LncRNA DICER1-AS1 promotes the proliferation, invasion and autophagy of osteosarcoma cells via miR-30b/ATG5.

Osteosarcoma is a prevalent primary malignant tumor and long non-coding RNAs (lncRNAs) have been validated to modulate the osteosarcoma tumorigenesis. In present study, our research team investigates the role of a novel identified lncRNA DICER1-AS1 on the tumor progression and autophagy. Results showed that lncRNA DICER1-AS1 was up-regulated in osteosarcoma cells using microarray analysis and RT-PCR. Cellular functional experiments revealed that DICER1-AS1 knockdown suppressed the proliferation, migration, invasion and autophagy of osteosarcoma cells in vitro. Besides, DICER1-AS1 knockdown inhibited the protein expression levels of ATG5, LC3-II and Beclin 1, suggesting the inhibition on the autophagy of osteosarcoma cells. Moreover, miR-30b was verified to target 3'-UTR of DICER1-AS1 and ATG5 using bioinformatics tools and luciferase reporter assay or RNA-immunoprecipitation (RIP). Western blot showed that ATG5 protein expression was decreased in DICER1-AS1 knockdown and miR-30b mimics transfected cells, while increased in miR-30b inhibitor transfected cells, presenting a negative correlation with miR-30b and a positive correlation with DICER1-AS1. Finally, xenograft assay in vivo indicated that DICER1-AS1 knockdown inhibited the osteosarcoma tumor growth and protein expression level of ATG5. In summary, all the results conclude that DICER1-AS1 regulates the proliferation, invasion and autophagy of osteosarcoma via miR-30b/ATG5 axis, providing a novel insight for osteosarcoma tumorigenesis.