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Intervertebral disc degeneration (IDD) is considered the basis of serious clinical symptoms, especially for low back pain (LBP). Therefore, it is essential to explore the regulatory role and diagnostic performance of dysregulated genes and potential drugs in IDD. Through WGCNA co-expression analysis, 36 co-expression modules were obtained. Among them, MidnightBlue and Red modules were the most related to IDD. Functional enrichment analysis showed that the Red module was mainly related to neutrophil activation and regulation of cytokine-mediated signaling pathway and apoptosis, whereas the MidnightBlue module was mainly related to extracellular matrix organization, bone development, extracellular matrix, extracellular matrix component, and other extracellular matrices. Furthermore, 356 genes highly related to the module were screened to construct a protein interaction network. Network degree distribution analysis showed that the known IDD-related genes had a higher degree of distribution. Enrichment analysis demonstrated that these genes were enriched in MAPK_SIGNALING_PATHWAY (FDR = 0.012), CHEMOKINE_SIGNALING_PATHWAY, and some other pathways. By constructing a disease-gene interaction network, three disease-specific genes were finally identified. Through combining with the drug-target gene interaction network, two potential therapeutic drugs, entrectinib and larotrectinib, were determined. Finally, based on these genes, the diagnostic model in the training dataset, test dataset, and verification dataset all showed a high diagnostic performance. The findings of this study contributed to the diagnosis of IDD and personalized treatment of IDD.

ObjectivesThe purpose of the present study was to simultaneously examine the transcript levels of a large number of interleukins (ILs; IL-9, IL-10, IL-12, IL-13, IL-16, IL-17, IL-18, IL-26, and IL-27) and investigate their correlation with the clinicopathological profiles of patients with tuberculous intervertebral discs.MethodsClinical data were collected from 150 patients participating in the study from January 2013 to December 2013. mRNA expression levels in 70 tuberculous, 70 herniated, and 10 control intervertebral disc specimens were determined by real-time polymerase chain reaction.ResultsIL-10, IL-16, IL-17, IL-18, and IL-27 displayed stronger expression in tuberculous spinal disc tissue than in normal intervertebral disc tissue (P<0.05). Our results illustrated multiple correlations among IL-10, IL-16, IL-17, IL-18, and IL-27 mRNA expression in tuberculous samples. Smoking habits were found to have a positive correlation with IL-17 transcript levels and a negative correlation with IL-10 transcript levels (P<0.05). Pain intensity, symptom duration, C-reactive protein levels, and the erythrocyte sedimentation rate exhibited multiple correlations with the transcript levels of several ILs (P<0.05).ConclusionsThe experimental data imply a double-sided effect on the activity of ILs in tuberculous spinal intervertebral discs, suggesting that they may be involved in intervertebral discs destruction. Our findings also suggest that smoking may affect the intervertebral discs destruction process of spinal tuberculosis. However, further studies are necessary to elucidate the exact role of ILs in the intervertebral discs destruction process of spinal tuberculosis.

Adriamycin (ADM) is a first‑line agent administered during the therapeutic regimes against osteosarcoma. Clinical administration of ADM produces systemic toxicity and resistance in patients, which restricts its applicability. In the present study the effects of phenethyl isothiocyanate (PEITC) on ADM‑induced apoptosis in osteosarcoma cells was evaluated. Using U2‑OS osteosarcoma cell line cells, treatment with PEITC or ADM for 24 h was observed to dose‑dependently inhibit proliferation of U2‑OS cells with half maximal inhibitory concentration (IC50) values of 5.33 µM and 10.32 µg/ml, respectively. When U2‑OS cells were treated with a combination of the two agents, the inhibition was apparently enhanced, as the IC50 values decreased to 2 µM for PEITC and 1 µg/ml for ADM. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed that treatment with PEITC or ADM alone reduced the viability of the U2‑OS cells. Furthermore, the viability of the U2‑OS cells was additionally reduced when treatment was with PEITC and ADM together. Supporting this finding, the activity and expression of caspase‑3 were observed to be enhanced in the U2‑OS cells following treatment with either PEITC or ADM, or a combination of the two. These results clearly indicate that PEITC enhances ADM‑induced apoptosis in osteosarcoma cells.