Osteoarthritis (OA), an inflammatory form of arthritis, is characterized by synovial inflammation and cartilage destruction largely influenced by two key proinflammatory cytokines—interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Notably, levels of visfatin (a proinflammatory adipokine) are elevated in patients with OA, although the relationship of visfatin to IL-6 and TNF-α expression in OA pathogenesis has been unclear. In this study, visfatin enhanced the expression of IL-6 and TNF-α in human OA synovial fibroblasts (OASFs) in a concentration-dependent manner and stimulation of OASFs with visfatin promoted phosphorylation of extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), while ERK, p38, and JNK inhibitors or siRNAs all abolished visfatin-induced increases in IL-6 and TNF-α production. Moreover, transfection with miR-199a-5p mimics reversed visfatin-induced increases in IL-6 and TNF-α production. Furthermore, we also found that visfatin-promoted IL-6 and TNF-α production is mediated via the inhibition of miR-199a-5p expression through the ERK, p38, and JNK signaling pathways. Visfatin may therefore be an appropriate target for drug intervention in OA treatment.

Osteoarthritis (OA) pannus contains a network of neovascularization that is formed and maintained by angiogenesis, which is promoted by vascular endothelial growth factor (VEGF). Bone marrow-derived endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation in OA. The adipokine visfatin stimulates the release of inflammatory cytokines during OA progression. In this study, we found significantly higher visfatin and VEGF serum concentrations in patients with OA compared with healthy controls. We describe how visfatin enhanced VEGF expression in human OA synovial fibroblasts (OASFs) and facilitated EPC migration and tube formation. Treatment of OASFs with PI3K and Akt inhibitors or siRNAs attenuated the effects of visfatin on VEGF synthesis and EPC angiogenesis. We also describe how miR-485-5p negatively regulated visfatin-induced promotion of VEGF expression and EPC angiogenesis. In our OA rat model, visfatin shRNA was capable of inhibiting visfatin and rescuing EPC angiogenesis and pathologic changes. We detail how visfatin affected VEGF expression and EPC angiogenesis in OASFs by inhibiting miR-485-5p synthesis through the PI3K and Akt signaling pathways.

Background: Diabetes and sarcopenia are verified as mutual relationships, which seriously affect the quality of life of the elderly. Endothelin-1 is well investigated, is elevated in patients with diabetes, and is related to muscle cellular senescence and fibrosis. However, the mechanism of ET-1 between diabetes and myopathy is still unclear. The aim of this study was to evaluate the prevalence of sarcopenia in the elderly with diabetes and to clarify its relationship with ET-1 molecular biological mechanism, progress as well as changes in muscle and fat.

Background: Haglund’s deformity, which is characterized by a bony prominence of the posterosuperior aspect of the calcaneus, causes posterior heel pain. To date, there is no standard radiographic parameter to diagnose symptomatic Haglund’s deformity. Herein, we proposed novel radiographic measurements to distinguish between patients with and without symptomatic Haglund’s deformity. Methods: We retrospectively evaluated ankle radiographs of 43 patients who underwent surgery for symptomatic Haglund’s deformity (Haglund group) and 41 healthy individuals (control group) free of heel complaints. Fowler–Phillip angle (FPA), Heneghan–Pavlov parallel pitch lines (PPL), Haglund’s deformity height, bump height, and bump-calcaneus ratio were measured and compared between the groups. Furthermore, the reliability and cut-off value of each parameter were validated via ICC and ROC curve analysis, respectively. Results: The bump height (p < 0.001) and the bump-calcaneus ratio (p < 0.001) showed significant differences between the control and Haglund groups, unlike FPA, PPL, and Haglund’s deformity height. ROC curve analysis revealed that the AUC of bump-calcaneus ratio was larger than that of bump height. The optimal threshold was 4 mm or higher for bump height and 7.5% or higher for bump-calcaneus ratio. The intra- and inter- observer ICCs were, respectively, 0.965 and 0.898 for bump height and 0.930 and 0.889 for bump-calcaneus ratio. Conclusions: This study proposes two novel radiographic parameters to identify operatively treated Haglund’s deformity, namely bump height and bump-calcaneus ratio. They are easy to measure and intuitive. Both of them are effective diagnostic parameters for Haglund’s deformity. Furthermore, bump-calcaneus ratio is more reliable diagnostic parameter than bump height.

Objective: Oral squamous cell carcinoma (OSCC) constitutes almost 90% of head and neck malignancies and has a poor prognosis. To improve the efficacy of OSCC therapy, it is of great significance to explore other therapy for OSCC. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, is implicated in cancer pathogenesis. Moreover, ET-1 promotes epithelial-mesenchymal transition (EMT) during the development of human cancers. We further to found that ET-1 exposure induced EMT in human squamous cell carcinoma cell lines SCC4 and SAS, by enhancing the expression of EMT biomarkers N-cadherin and vimentin and reducing E-cadherin expression via upregulation of the transcription factor TWIST. Materials and Methods: Cell motility was examined by migration, invasion and wound-healing assays. Quantitative real time polymerase chain reaction (q-PCR), and promoter assays confirmed the inhibitory effects of ET-1 on miRNAs expression in oral cancer cells. We demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor using image analysis software. Results: In addition, ET-1/ETAR reduced levels of microRNA-489-3p (miR-489-3p), a transcriptional repressor of TWIST. We have identified a novel bypass mechanism through which ET-1/ETAR are involved in TWIST signaling and downregulate miR-489-3p expression, enabling OSCC cells to acquire the EMT phenotype. Notably, ET-1 knockdown dramatically decreased levels of EMT markers and cell migration potential. Conclusion: The role of ET-1 in OSCC progression is supported by our findings from an in vivo murine model of OSCC. ET-1 may therefore represent a novel molecular therapeutic target in OSCC metastasis.