Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes in vitro. In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.

Ubiquitin Conjugating Enzyme 2C (UBE2C) is an emerging target gene for tumor progression. However, the tumorigenic effect and mechanism of UBE2C in adrenocortical carcinoma (ACC) remains unclear. Systematic investigation of the tumorigenic effect of UBE2C may help in understanding its prognostic value in adrenocortical carcinoma. First, we exploited the intersection on DFS-related genes, OS-related genes, highly expressed genes in adrenocortical carcinoma as well as differentially expressed genes (DEGs) between tumor and normal, and then obtained 20 candidate genes. UBE2C was identified to be the most significant DEG between tumor and normal. It is confirmed that high expression of UBE2C was strongly associated with poor prognosis in patients with ACC by analyzing RNA-seq data of ACC obtained from the Cancer Genome Atlas (TCGA) database implemented by ACLBI Web-based Tools. UBE2C expression could also promote m6A modification and stemness in ACC. We found that UBE2C expression is positively associated with the expression of CDC20, CDK1, and CCNA2 using ACLBI Web-based Tools, indicated the hyperactive cell cycle progression present in ACC with high UBE2C expression. In addition, UBE2C knockdown could significantly inhibit the proliferation, migration, invasion, EMT of adrenocortical carcinoma cells as well as the cell cycle progression in vitro. Notably, pan-cancer analysis also identified UBE2C as an oncogene in various tumors. Taken together, UBE2C was strongly associated with poor prognosis of patients with ACC by promoting cell cycle progression and EMT. This study provides a new theoretical basis for the development of UBE2C as a molecular target for the treatment of ACC.

Background: Recurrent intervertebral disc herniation and an exacerbated degenerative process have been identified as the most important factors contributing to persistent pain and disability after surgical discectomy.Defects in the annulus fibrosus remain a surgical challenge, as the preference for minimally invasive surgical approaches for lumbar microdiscectomy, surgical access, and the specifics of anatomy limit the types of devices that permit annulus fibrosus repair. Furthermore, the intervertebral disc is a relatively avascular structure, and surgical procedures can accelerate the degenerative disc process. This study aimed to evaluate the clinical safety and efficacy of a novel microdiscectomy annular repair technique combined with an autologous conditioned plasma (ACP) intradiscal injection for the treatment of lumbar disc herniation (LDH).Methods: From July 2017 to December 2018 this study recruited 75 patients with LDH (single segment) and randomly divided these patients into the following three groups: group A, full endoscopic discectomy; group B: full endoscopic discectomy and annular repair; group C, full endoscopic discectomy annular repair and ACP intradiscal injection. The pre-and postoperative neurological function and pain status were evaluated by the visual analog scale (VAS) score and the Oswestry disability index (ODI). Patients were followed up once preoperatively, and at 1, 3, and 6 months postoperatively. Results:The procedure was successfully performed in all cases. No cases required conversion to an open procedure. The preoperative symptoms were alleviated significantly after surgery. The VAS scores for lower back and lower limb pain and ODI score were significantly difference at 1 month, 3 months, 6 months post operation compared to pre-operation scores (P<0.05). For VAS scores of the lower back, the difference between group A and group C was statistically significant (A>C), as was the difference between group B and group C (B>C). Conclusions:Early results showed that the use of the novel full endoscopic annular repair technique and ACP intradiscal injection serial therapeutic model are beneficial for short term outcomes and demonstrates a reduction in symptomatic disc reherniation with low postoperative complication rates. This new serial therapeutic model may significantly improve the symptoms of postoperative lower back pain.

Objective: To explore the possibility and mechanism of targeted blocking SDF-1/CXCR4 signaling pathway using three antagonists TN14003, T140, and AMD3100 in vivo, and to investigate the function of three antagonists in delay degeneration process of articular cartilage. Methods: Ninety-six male Duncan-Hartley guinea pigs (6 months old) were divided into groups A, B, C, and D randomly. Alzet trace pump was implanted in the back subcutaneous tissue of pigs in group A, and TN14003 with concentration of 180 μg/ml was pumped every day. Alzet trace pump was implanted in the back subcutaneous tissue of pigs in group B, and T140 with concentration of 180 μg/ml was pumped every day. Alzet trace pump was implanted in the back subcutaneous tissue of pigs in group C, and AMD3100 with concentration of 180 μg/ml was pumped every day. Hartley guinea pigs in group D remained untreated as the blank control group. At 2, 4, 6, 8, 10, and 12 weeks of treatment, 5 to 8 animals in each group were randomly chosen for blood collection via cardiac puncture. SDF-1 content using enzyme-linked immunosorbent assay (ELISA). At 12 weeks, all guinea pigs were sacrificed by injecting pentobarbital sodium (30 mg/kg) into the peritoneal cavity. Cartilages from the tibial plateau in each group were harvested for PCR testing and western blot analysis. SPSS19.0 was used for data analysis.

Background: Deep vein thrombosis (DVT) is an early postoperative complication. Thrombosis formation, which is potentially life-threatening, seriously affects the rehabilitation of patients after surgery. We aimed to establish a C57 mouse model of DVT and to examine the changes in the expression of Krüppel-like factor 15 (KLF15) and endothelial nitric oxide synthase (eNOS) in venous wall tissues, and we also investigated the regulatory relationship of KLF15 and eNOS in the thrombin-induced human umbilical vein endothelial cell (HUVEC) injury cell model. Methods:The DVT model was established using the inferior vena cava (IVC) stenosis method. The expression levels of KLF15 and eNOS were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In cell experiments, the expression of KLF15 and eNOS was analyzed in the model of thrombin-induced HUVEC injury with KLF15 siRNA.Results: Compared to the control and sham-operated groups, KLF15 in the DVT group was upregulated, while eNOS was downregulated. The results of cell experiments revealed that KLF15 was downregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. Meanwhile, eNOS was upregulated in the thrombin+KLF15 siRNA group compared with the thrombin group. These findings suggested that KLF15 regulated the expression of eNOS in the DVT model. Conclusions:We successfully constructed a DVT mouse model. In the early stage of DVT formation, KLF15 regulated the expression and inhibited the antithrombotic effect of eNOS, resulting in thrombi formation.

Background Gene regulatory network analysis has found that long noncoding ribonucleic acids (lncRNAs) are strongly associated with the pathogenesis of osteoarthritis. Objectives To determine the differential expression of lncRNAs and microRNAs (miRNAs) in normal chondrocytes and those from a model of articular chondrocyte degeneration. Methods Chondrocytes were cultured from cartilage obtained from patients diagnosed with osteoarthritis of the knee. Stromal cell-derived factor-1 (SDF-1) was used to induce their degeneration. Total RNA was extracted, analyzed, amplified, labeled, and hybridized on a chip to determine expression. The set of enriched differentially expressed miRNAs was analyzed by gene ontology and the Kyoto Encyclopedia of Genes and Genomes to describe the functional properties of the key biological processes and pathways. We conducted a bioinformatics analysis using Cytoscape to elucidate the interactions between miRNAs and proteins. Results We found that the expression of 186 lncRNAs was significantly different in the model of chondrocyte degeneration, in which 88 lncRNAs were upregulated, and 98 were downregulated. Expression of 684 miRNAs was significantly different. Analysis of the protein–protein interaction (PPI) network indicated that the genes for CXCL10, ISG15, MYC, MX1, OASL, IFIT1, RSAD2, MX2, IFI44L, and BST2 are the top 10 core genes, identifying the most important functional modules to elucidate the differential expression of miRNAs. Conclusions These data may provide new insights into the molecular mechanisms of chondrocyte degeneration in osteoarthritis, and the identification of lncRNAs and miRNAs may provide potential targets for the differential diagnosis and therapy of osteoarthritis.

Background With the in-depth exploration of the gene regulation network associated with the pathogenesis of osteoarthritis (OA), lncRNA has been found to play a major role in regulating the development of osteoarthritis. In this study, the expressions of miRNAs and lncRNAs in chondrocytes (2 days) of SDF-1-induced articular chondrocyte degeneration model and in normal chondrocytes were detected and the difference between them was visualized. The bioinformatics analysis was performed in parallel to elucidate the interactions between miRNAs and protein molecules. Results It was found that 186 lncRNA changes had significant statistical differences, of which 88 lncRNA were up-regulated and 98 lncRNA were down-regulated. A total of 684 miRNA had significant statistical differences in their expression changes. Gene Ontology and Kyoto Encyclopedia of Genes were performed for the gene set enrichment analysis to determine the key biological processes and pathways. The protein-protein interaction (PPI) network indicated that CXCL10, ISG15, MYC, MX1, OASL, FIICT1, RSAD2, MX2, IFI44, and LBST2 are the ten core genes. The PPI network identified the most important functional modules to elucidate the differential expression of miRNA. Conclusions These data may provide new insights into the molecular mechanisms of osteoarthritis chondrocyte degeneration, and the identification of lncRNA and miRNA can provide potential therapeutic targets for the diagnosis and differential diagnosis of osteoarthritis.