Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-β and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-β can control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-β signaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-β and ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression. The mutual collaboration of TGF-β and ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies.

located between cementum and alveolar bone has important role in regeneration of periodontal tissues damaged by mechanical or biochemical factors (Ozer et al., 2013). In order to maintain PDL homeostasis in both normal and pathologic conditions, resident PDL multipotent progenitors, or stem cell-like cells (PDLSCs) act depending on local tissue demands, since PDLSCs can differentiate into major cellular constituents of PDL, such are osteoblast, fibroblast, and cementoblasts, thus maintaining PDL structure and function (Bassir et al., 2016;Han, Menicanin, Gronthos, & Bartold, 2014;Liu et al., 2015;Mao, Robey, & Prockop, 2012;Zhu & Liang, 2015).Oral cavity presents host niche for pathogenic bacteria which may provoke host tissue inflammation, damage dental tissues homeostasis, and finally lead to gingivitis or periodontitis (Chatzivasileiou, Kriebel, Steinhoff, Kreikemeyer, & Lang, 2015), as well as various systemic diseases (Nagpal, Yamashiro, & Izumi, 2015;Seymour, Ford, Cullinan, Leishman, & Yamazaki, 2007 bovine serum (FBS; Capricorn-Scientific, Germany), 100 U/ml penicillin and 100 μg/ml streptomycin (Gibco, Thermo Fisher Scientific), and incubated at 37°C in humidified atmosphere containing 5% CO 2 (standard conditions). The medium was replaced twice a week, and after reaching the 90% of confluence, the cells were detached using 0.25% solution of trypsin/EDTA (Gibco). All experiments were performed using PDLSCs between passage two and six.Human peripheral blood mononuclear cells (MNCs) were isolated from fresh heparinized blood collected from 15 healthy voluntary unrelated donors by density gradient using lymphocyte separation medium Lymphocyte Separation Medium 1.077 g/ml (CapricornScientific). Purified MNCs were cultivated in RPMI-1640 medium (Sigma-Aldrich) supplemented with 10% FBS, 2 mM L-glutamine, 1 mM sodium pyruvate, 100 U/ml penicillin, and 100 μg/ml streptomycin in standard conditions.Human endothelial cell line (EA.hy926) was purchased from The American Type Culture Collection (ATCC, CRL-2922), MD, and cultured in GM in standard conditions. antibodies (Thermo Scientific) and CD14 (Sigma-Aldrich). The percentage of nonspecific binding was determined by using the appropriate FITC-and PE-conjugated isotype control antibodies (R&D Systems). Flow cytometry was performed using flow cytometer Cytomics FC 500 (Beckman Coulter). | Phenotype analysis | Multilineage differentiationFor evaluation of multilineage differentiation capacity PDLSCs were cultivated in GM or corresponding differentiation medium (DM) with orwithout LPS (1000 ng/ml, purchased from Sigma-Aldrich) in standard conditions. Osteogenic DM contained DMEM supplemented with 5% FBS, 100 U/ml penicillin/streptomycin, 50 µM ascorbic acid-2-phosphate (Sigma-Aldrich), and 10 mM β-glycerophosphate (SigmaAldrich). For osteogenic differentiation detection, alkaline phosphatase (ALP) staining has been followed after 7 days of cultivation, while calcium in DMEM, 100 U/ml penicilin/streptomycin, 100 µg/ml isobutylmethylxanthine (IBMX; Sigma-Aldrich),...

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Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.

The results obtained demonstrated that both MSCs represent good alternative sources of adult MSCs that could be used in cell therapy applications.

The present study evaluated the role of interleukin (IL) 17 in multilineage commitment of C2C12 myoblastic cells and investigated associated signaling pathways. The results concerning the effects on cell function showed that IL-17 inhibits the migration of C2C12 cells, while not affecting their proliferation. The data regarding the influence on differentiation demonstrated that IL-17 inhibits myogenic differentiation of C2C12 cells by down-regulating the myogenin mRNA level, myosin heavy chain expression and myotube formation, but promotes their osteogenic differentiation by up-regulating the Runt-related transcription factor 2 mRNA level, cyclooxygenase-2 expression and alkaline phosphatase activity. IL-17 exerted these effects by activating ERK1,2 mitogen activated protein kinase signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. Additional analysis showed that the induction of osteogenic differentiation by IL-17 is independent of BMP signaling. The results obtained demonstrate the potential of IL-17 not only to inhibit the myogenic differentiation of C2C12 myoblasts but also to convert their differentiation pathway into that of osteoblast lineage providing new insight into the capacities of IL-17 to modulate the differentiation commitment.