Glioblastoma (GBM) is one of the most common malignant and incurable brain tumors. The identification of a gene signature for GBM may be helpful for its diagnosis, treatment, prediction of prognosis and even the development of treatments. In this study, we used the GSE108474 database to perform GSEA and machine learning analysis, and identified a 33-gene signature of GBM by examining astrocytoma or non-GBM glioma differential gene expression. The 33 identified signature genes included the overexpressed genes COL6A2, ABCC3, COL8A1, FAM20A, ADM, CTHRC1, PDPN, IBSP, MIR210HG, GPX8, MYL9 and PDLIM4, as well as the underexpressed genes CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C, SHANK2 and VIPR2. Protein functional analysis by CELLO2GO implied that these signature genes might be involved in regulating various aspects of biological function, including anatomical structure development, cell proliferation and adhesion, signaling transduction and many of the genes were annotated in response to stress. Of these 33 signature genes, 23 have previously been reported to be functionally correlated with GBM; the roles of the remaining 10 genes in glioma development remain unknown. Our results were the first to reveal that GBM exhibited the overexpressed GPX8 gene and underexpressed signature genes including CHST9, CSDC2, ENHO, FERMT1, IGFN1, LINC00836, MGAT4C and SHANK2, which might play crucial roles in the tumorigenesis of different gliomas.

Osteoarthritis (OA) is characterized by the infiltration and adhesion of monocytes into the inflamed joint synovium. Interleukin (IL)-17 is a critical inflammatory mediator that participates in the progression of OA, although the mechanisms linking IL-17 and monocyte infiltration are not well understood. Our analysis of synovial tissue samples retrieved from the Gene Expression Omnibus (GEO) dataset exhibited higher monocyte marker (CD11b) and vascular cell adhesion molecule 1 (VCAM-1) levels in OA samples than in normal, healthy samples. The stimulation of human OA synovial fibroblasts (OASFs) with IL-17 increased VCAM-1 production and subsequently enhanced monocyte adhesion. IL-17 affected VCAM-1-dependent monocyte adhesion by reducing miR-5701 expression through the protein kinase C (PKC)-α and c-Jun N-terminal kinase (JNK) signaling cascades. Our findings improve our understanding about the effect of IL-17 on OA progression and, in particular, VCAM-1 production and monocyte adhesion, which may help with the design of more effective OA treatments.

Chondrosarcoma is the primary malignancy of bone that is characterized by a potent capacity to invade locally and cause distant metastasis, and is therefore associated with poor prognoses. Chondrosarcoma further shows a predilection for metastasis to the lungs. The brain-derived neurotrophic factor (BDNF) is a small molecule in the neurotrophin family of growth factors that is associated with the disease status and outcome of cancers. However, the effect of BDNF on cell motility in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma cell lines had significantly higher cell motility and BDNF expression compared to normal chondrocytes. We also found that BDNF increased cell motility and expression of matrix metalloproteinase-1 (MMP-1) in human chondrosarcoma cells. BDNF-mediated cell motility and MMP-1 up-regulation were attenuated by Trk inhibitor (K252a), ASK1 inhibitor (thioredoxin), JNK inhibitor (SP600125), and p38 inhibitor (SB203580). Furthermore, BDNF also promoted Sp1 activation. Our results indicate that BDNF enhances the migration and invasion activity of chondrosarcoma cells by increasing MMP-1 expression through a signal transduction pathway that involves the TrkB receptor, ASK1, JNK/p38, and Sp1. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.

Osteoarthritis (OA) is a painful, progressive chronic inflammatory disease marked by cartilage destruction. Certain synovial inflammatory cytokines, such as IL-1β and TNF-α, promote OA inflammation and pain. Lactobacillus spp. is a well-known probiotic with anti-inflammatory, analgesic, antioxidant, and antiosteoporotic properties. This study evaluated the therapeutic effects of a live L. plantarum strain (GKD7) in the anterior cruciate ligament transection (ACLT)-induced OA rat model. The results show that oral administration of live L. plantarum GKD7 improved weight-bearing asymmetry after ACLT surgery. Moreover, micro-computed tomography images and histopathological analysis show that oral live L. plantarum GKD7 improved subchondral bone architecture, protected articular cartilage against ACLT-induced damage, and reduced synovial inflammation. L. plantarum GKD7 also reduced IL-1β and TNF-α production in OA cartilage and synovium. Thus, orally administered live L. plantarum GKD7 appears to effectively slow the progression of OA.

Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

Osteoarthritis (OA) is a degenerative and painful inflammatory joint disease affecting the cartilage, bone, and synovial membranes, without any effective treatment that targets the underlying mechanisms of OA. Our study evaluated the therapeutic effects of a live probiotic strain, Clostridium butyricum GKB7, administered for 6 weeks to rats with knee OA (KOA) induced by anterior cruciate ligament transection (ACLT) of the right knee. All rats underwent weekly weight-bearing behavioral testing and body weight measurements. At 6 weeks, all rats were sacrificed, and the right hind knees were collected for micro-computed tomography imaging and histopathological and immunohistochemical analyses. Compared with rats in the ACLT-only group, ACLT rats administered the probiotic exhibited dramatic improvements in pain-related behavior from postoperative week 2, had significantly less osseous and cartilaginous damage at week 6, and significantly lower levels of the inflammatory markers interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in cartilage and synovium sections. C. butyricum GKB7 appeared to slow or even reverse OA progression and is worth investigating as a novel therapeutic for OA.