The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin-8 (IL-8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL-8, during which neutrophils are recruited to the implanted site and are N2-polarized, which then secrete stromal cell-derived factor-1 (SDF-1 ) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF-1/CXCR4 (C-X-C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and -catenin-mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil-initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.

Oxidized low-density lipoprotein (oxLDL) is involved in the pathological phenotypic transformation of vascular smooth muscle cells in atherosclerosis. Galectin-3 also has an important role in atherosclerosis. However, little is currently known regarding the effects of galectin-3 on the oxLDL-induced phenotypic transformation of vascular smooth muscle cells. In the present study, primary culture human umbilical vascular smooth muscle cells were treated with various oxLDL concentrations (0-50 μg/ml) for 72 h, and phenotypic changes were subsequently recorded. The results of the present study suggested that oxLDL increases the expression levels of galectin-3, and induces the phenotypic transformation of vascular smooth muscle cells. The oxLDL-induced cells exhibited increased expression levels of osteopontin, a smooth muscle synthetic protein, and calponin and α-actin, smooth muscle contractile proteins. The oxLDL-induced changes in cellular phenotype were associated with increased migration, proliferation, and phagocytosis. Concordant with these results, oxLDL-treated smooth muscle cells exhibited activation of canonical Wnt signaling, as determined by an increase in the protein expression levels of β-catenin. Silencing of galectin-3 by small interfering RNA reversed the phenotypic transformation and functional changes observed in the oxLDL-treated cells, suggesting these changes were dependent on the activation of galectin-3. In addition, galectin-3 knockdown decreased the protein expression levels of β-catenin in both the cytoplasm and nucleus; however, the mRNA expression levels of β-catenin remained unchanged. These results suggest that galectin-3 is responsible for the phenotypic transformation of human umbilical vascular smooth muscle cells, and the canonical Wnt/β-catenin signaling pathway may be involved in this process.

Galectin‑3, a galactoside‑binding protein, is highly expressed in carotid plaques and plays an important role in the atherosclerotic lesions. The phenotype transformation of vascular smooth muscle cells is the basic pathological change of atherosclerosis. This study investigated the effects of exogenous galectin‑3 on the function and phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC). In this study, we treated vascular smooth muscle cells with recombinant galectin‑3 and tested its effect on cell proliferation, migration, and phenotype transformation. Our results showed that exogenous galectin‑3 promoted human umbilical vascular smooth muscle cells (HUSMC) proliferation and migration. Exogenous galectin‑3 enhanced the expression of the smooth muscle synthetic protein osteopontin, smooth muscle contractile proteins calponin and smooth muscle α‑actin. The galectin‑3‑induced change in cell phenotype was associated with the activation of canonical Wnt signaling, as measured by β‑catenin axin2 and cyclin D1 expression. β‑catenin inhibition by small interfering RNA reduced cell proliferation, decreased cell motility, and blocked galectin‑3‑induced phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC). Our data suggest galectin‑3 promotes the phenotype transformation of human umbilical vascular smooth muscle cells (HUSMC) by activating Wnt/β‑catenin signaling pathway.

ObjectiveApproximately, 10–20% of patients with drug eluting stent (DES) in-stent restenosis (ISR) will develop recurrent ISR; yet, the optimal management of recurrent DES-ISR is unknown. We sought to compare the outcomes of recurrent DES-ISR treated with drug eluting balloons (DEB) to those with repeated implantation of new-generation DES.MethodsA total of 172 patients with recurrent DES-ISR were enrolled and stratified into two cohorts: the repeated DES implantation (Re-DES) group and the DEB group. The primary endpoint was the 1-year incidence of major adverse cardiovascular events (MACE).ResultsNinety-three patients treated with DEB and 79 patients with Re-DES implantation were analyzed. Both groups had comparable baseline characteristics. Lesser residual stenosis was achieved in the Re-DES group (11.3 ± 3.2% vs. 22.4 ± 4.3%; P = 0.00) than in the DEB group. However, the incidence of MACE and target lesion revascularization (TLR) were less in the DEB group (17.2% vs. 32.9%; P = 0.02 and 15.1% vs. 27.8%; P = 0.04, respectively). For the ≥3 metal-layered DES-ISR subgroup, DEB drastically reduced the incidences of MACE and TLR compared with Re-DES (20.0% vs. 57.9%; P = 0.02 and 16.0% vs. 47.4%; P = 0.04, respectively). Survival analysis demonstrated that MACE-free survival was significantly higher in the DEB group compared with the Re-DES group, whether the metal layers were ≥3 or 2. Multivariate analysis revealed that the risk factors of MACE were diabetes mellitus, ≥3 metal-layered DES ISR, and repeat DES deployment.ConclusionsFor recurrent DES-ISR, DEB may improve clinical outcomes compared with Re-DES implantation, especially for ≥3 metal-layered DES-ISR.