Melatonin: A regulator of the interplay between FoxO1, miR96, and miR215 signaling to diminish the growth, survival, and metastasis of murine adenocarcinoma.

Melatonin (Mel.), also known as the magic hormone, is a nocturnally secreted hormone orchestrates the clearance of free radicals that have been built up and cumulated during day. This study aims to detect the impact of pineal gland removal on the incidence of tumor development and to assess the signaling pathways via which exogenous melatonin counteract cancer growth. This goal has been achieved by novel approach for pineal destruction using dental micromotor which validated by melatonin downregulation in blood plasma. Mice were injected sub-cutenously with Ehrlich cells to develop solid tumor as a murine model of breast cancer. The increase at tumor markers carcino embryonic antigen, TNFα, and nuclear factor kappa-light-chain-enhancer of activated B cells was over countered by exogenous melatonin supplementation (20 mg/kg) daily for 1 month. The anticancer effects of melatonin were significantly mediated by scavenging H2 O2 and NO and diminishing of lipid peroxidation marker malondialdehyde. The real-time polymerase chain Rx analyses indicated a significant effect of Melatonin in upregulating the expression of miR215, fork head box protein O1 (foxO1), and downregulation of miR96. Flowcytometric analyses indicated a significant effect of melatonin on induction of cell cycle arrest at G1 phase which was further confirmed by Ki67 downregulation. Immunohistochemical analyses indicated the role of melatonin in upregulating P53-dependent apoptosis and downregulating CD44 signaling for survivin, matrix metallo-protein kinase 2, and vascular endothelial growth factor to inhibit cell survival and metastasis. In conclusion, this study sheds the light on M./P53/miR215/CD44 with an emphasis on M./miR96//foxO1 signaling cascades, as a novel pathway of melatonin signaling in adenocarcinoma to diminish cancer cell growth, survival and metastasis.

Radio-sensitizing effect of a cocktail of phytochemicals on HepG2 cell proliferation, motility and survival.

Radio-resistance is a major hurdle challenging oncologist worldwide. Despite their anti-cancer characteristics, the implication of phytochemicals in clinical trials is still limited. This study is designed to evaluate the anticancer characteristics and radio-sensitizing effect of a cocktail of seven phytochemicals on HepG2 cells. Characterization of phytochemicals combination phenolic and flavonoids content as well as their scavenging activity were tested. The effective concentration of BSG that will be used as a radio-sensitizing dose was calculated using AlamarBlue assay. Treatment of HepG2 cells with BSG and/or ionizing radiations led to significant downregulation at cell proliferation as indicated by the decrease of colony formation ratio, proliferation marker (Ki67) expression as well as G2/M cell cycle arrest. The combined treatment stimulated P53-dependent apoptosis which was indicated by the significant increase of early apoptosis marker (Annexin V) expression, DNA fragmentation, expression of P53 & Bax and downregulation of Bcl2 expression. Combined treatment significantly attenuated HepG2 cell motility which was validated using wound healing migration assay and the significant reduction at CD95 expression. This study demonstrates the anti-cancer effect of BSG and its fundamental role in provoking cell responsiveness to IR leading to a significant inhibition at HepG2 cell proliferation, survival and migration.

A systematic review of the concept and clinical applications of Bone Marrow Aspirate Concentrate in Orthopaedics.

INTRODUCTION: Mesenchymal stem cells (MSC's) are believed to have multipotent plasticity with the capability to differentiate along multiple cell lineages such as cartilage, bone, tendon, muscle, and nerve. Such multipotency has the potential to play an important role in the repair and reconstruction of multiple tissues across a number of orthopaedic specialties. Bone marrow and fat are the most abundant and accessible source of MSC's with bone marrow aspirate the most commonly being reported to stimulate healing. METHODS: This review examines the current reported 20 Q2 clinical applications of bone marrow aspirate concentrate and its effectiveness. RESULTS: The published studies reported techniques of collection and preparation of BMAC in addition to its applications in a number of orthopaedic sub-specialities. Studies could be sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (31), reconstruction of osseous defects/non-union (20), treatment of avascular necrosis (9), repair of cartilage defects (8), treatment of sports injuries and tendon injury/repair (9), injection in regenerative therapy (4), treatment of spine conditions (4) including enhancing postoperative fusion and degenerative disc pathology and orthopaedic oncology (4). A few published studies combined the use of platelet-rich plasma (PRP) with BMAC (4) or compared them in different applications (5). CONCLUSIONS: BMAC has been used in bone, cartilage and tendon injuries with encouraging results.