Transforming growth factor‐beta (TGF‐β) induces the migration and mobilization of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF‐β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration, and mobilization of BM‐MSCs mediated by TGF‐β are unclear. In this study, we showed that TGF‐β activated noncanonical signaling molecules, such as Akt, extracellular signal‐regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF‐β type I receptor in human BM‐MSCs and murine BM‐MSC‐like ST2 cells. Inhibition of Rac1 by NSC23766 and Src by PP2 resulted in impaired TGF‐β‐mediated migration. These results suggested that the Smad‐independent, noncanonical signals activated by TGF‐β were necessary for migration. We also showed that N‐cadherin‐dependent intercellular interactions were required for TGF‐β‐mediated migration using functional inhibition of N‐cadherin with EDTA treatment and a neutralizing antibody (GC‐4 antibody) or siRNA‐mediated knockdown of N‐cadherin. However, N‐cadherin knockdown did not affect the global activation of noncanonical signals in response to TGF‐β. Therefore, these results suggested that the migration of BM‐MSCs in response to TGF‐β was mediated through N‐cadherin and noncanonical TGF‐β signals.

Bone morphogenetic protein (BMP) signaling and Notch signaling play important roles in tumorigenesis in various organs and tissues, including the breast. BMP-4 enhanced epithelial mesenchymal transition (EMT) and stem cell properties in both mammary epithelial cell line and breast carcinoma cell line. BMP-4 increased the expression of EMT biomarkers, such as fibronectin, laminin, N-cadherin, and Slug. BMP-4 also activated Notch signaling in these cells and increased the sphere forming efficiency of the non-transformed mammary epithelial cell line MCF-10A. In addition, BMP-4 upregulated the sphere forming efficiency, colony formation efficiency, and the expression of cancer stem cell markers, such as Nanog and CD44, in the breast carcinoma cell line MDA-MB-231. Inhibition of Notch signaling downregulated EMT and stem cell properties induced by BMP-4. Down-regulation of Smad4 using siRNA impaired the BMP-4-induced activation of Notch signaling, as well as the BMP-4-mediated EMT. These results suggest that EMT and stem cell properties are increased in mammary epithelial cells and breast cancer cells through the activation of Notch signaling in a Smad4-dependent manner in response to BMP-4.

Raoultella spp. have recently been separated from the genus Klebsiella based on their molecular characteristics. It was discovered that Raoultella ornithinolytica can be misidentified as Klebsiella oxytoca by commonly used phenotypic identification systems. Therefore, this study evaluated the ability of three phenotypic systems to identify R. ornithinolytica compared with the genotypic methods sequence-specific primer PCR (SSP-PCR), 16S rRNA gene sequence analysis using the MicroSeq 500 system16S rDNA bacterial identification system or comparison with GenBank sequences using BLAST. The phenotypic systems examined in this study were the VITEK 2 GN ID card, the MicroScan Neg Combo 32 panel and API 20E. The SSP-PCR panel was able to distinguish the R. ornithinolytica reference strain from other Raoultella spp. and K. oxytoca. Of the 27 isolates identified as R. ornithinolytica by SSP-PCR, VITEK 2 identified all of them as R. ornithinolytica. MicroScan and API identified 25 isolates (92.6 %) and 24 isolates (88.9 %) as K. oxytoca, respectively. These isolates were ornithine decarboxylase (ODC) negative in all three phenotypic systems. MicroSeq 500 identified 24 isolates (88.9 %) as R. ornithinolytica, whereas GenBank identification was heterogeneous. Of the 68 isolates identified as K. oxytoca by SSP-PCR, 66 isolates (97.1 %) were identified as K. oxytoca by VITEK 2, MicroScan and API. MicroScan and API require additional biochemical tests to differentiate between ODC-negative R. ornithinolytica and K. oxytoca.

Background: Three phenotypic identification systems (MicroScan, VITEK 2, and Crystal GP) were evaluated for their accuracy to identify coagulase-negative staphylococci (CNS). A total of 120 clinical isolates confirmed to be CNS via 16S rRNA sequencing and analysis with the MicroSeq 500 v2.0 database were assessed.

Wound healing is essential for the survival and tissue homeostasis of unicellular and multicellular organisms. The current study demonstrated that the neuropeptide substance P (SP) accelerated the wound healing process, particularly in the skin. Subcutaneous treatment of SP accelerated wound closing, increased the population of α-smooth muscle actin positive myofibroblasts, and increased extracellular matrix deposition at the wound site. Moreover, SP treatment enhances angiogenesis without a local increase in the expression levels of vascular endothelial growth factor and stromal cell-derived factor-1. Importantly, SP treatment increased both the population of circulating endothelial progenitor cells in the peripheral blood and in CD31 positive cells in Matrigel plugs. The tube forming potential of endothelial cells was also enhanced by SP treatment. The results suggested that the subcutaneous injection of SP accelerated the wound healing in the skin via better reconstitution of blood vessels, which possibly followed an increase in the systemic mobilization of endothelial progenitor cells and a more effective assembly of endothelial cells into tubes.