Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fibroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

Mesenchymal Stem Cell Isolation from Pulp Tissue and Co-Culture with Cancer Cells to Study Their Interactions.

Cancer as a multistep process and complicated disease is not only regulated by individual cell proliferation and growth but also controlled by tumor environment and cell-cell interactions. Identification of cancer and stem cell interactions, including changes in extracellular environment, physical interactions, and secreted factors, might enable the discovery of new therapy options. We combine known co-culture techniques to create a model system for mesenchymal stem cells (MSCs) and cancer cell interactions. In the current study, dental pulp stem cells (DPSCs) and PC-3 prostate cancer cell interactions were examined by direct and indirect co-culture techniques. Condition medium (CM) obtained from DPSCs and 0.4 µm pore sized trans-well membranes were used to study paracrine activity. Co-culture of different cell types together was performed to study direct cell-cell interaction. The results revealed that CM increased cell proliferation and decreased apoptosis in prostate cancer cell cultures. Both CM and trans-well system increased cell migration capacity of PC-3 cells. Cells stained with different membrane dyes were seeded into the same culture vessels, and DPSCs participated in a self-organized structure with PC-3 cells under this direct co-culture condition. Overall, the results indicated that co-culture techniques could be useful for cancer and MSC interactions as a model system.

Dental pulp stem cells (DPSCs) increase prostate cancer cell proliferation and migration under in vitro conditions.

Cancer as a multistep and complicated disease is regulated by several molecular and cellular events. Cancer treatment could be managed at the early stages when the tumor is confined in the tissue. However, disseminated cancer cells metastasize to other body parts and generate new tumors resulting in mortality. Mesenchymal stem cells (MSCs) are found in different body parts and helps adult tissue regeneration. The role of MSCs in cancer progression has emerged as one of the important aspects in cancer biology and is the aim of interest in recent years. In the current study, effects of Dental Pulp Stem Cells (DPSCs) on PC-3 prostate cancer cell proliferation and migration were conducted by cell proliferation, apoptosis, gene expression and cell migration analysis in vitro. Condition medium (CM) obtained from DPSCs increased cell proliferation of PC-3 cells and decreased apoptosis. Either administration of CM or trans well co-culture of DPSCs increased cell migration in scratch assay, confirmed by gene expression analysis of migratory genes including fibronectin, laminin and collagen type I (Col I). Furthermore, DPSCs participated in a self-organized structure with PC-3 cells in co-culture conditions. Overall, results indicated that DPSCs could promote PC-3 cancer cell proliferation and metastasis in co-culture conditions in vitro.

A new hope for obesity management: Boron inhibits adipogenesis in progenitor cells through the Wnt/ß-catenin pathway.

Obesity is a worldwide medical problem resulting in serious morbidity and mortality involving differentiation of pre-adipocytes into mature adipocytes (adipogenesis). Boron treatment has been reported to be associated with weight reduction in experimental animals; however, its effects on pre-adipocyte differentiation and anti-adipogenic molecular mechanisms are unknown. In this study, we demonstrate the inhibitory activities of boric acid (BA) and sodium pentaborate pentahydrate (NaB) on adipogenesis using common cellular models. Boron treatment repressed the expression of adipogenesis-related genes and proteins, including CCAAT-enhancer-binding protein α and peroxisome proliferator-activated receptor γ, by regulating critical growth factors and the ß-catenin, AKT, and extracellular signal-regulated kinase signaling pathways. In addition, although boron treatment did not induce apoptosis in pre-adipocytes, it depressed mitotic clonal expansion by regulation of cell cycle genes. Overall, these data offer promising insights into the prevention/treatment of obesity and associated diseases.

Dose-dependent Effect of Boric Acid on Myogenic Differentiation of Human Adipose-derived Stem Cells (hADSCs).

Boron, a vital micronutrient for plant metabolism, is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 µM) and high-dose (819.6 µM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron's effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.