Mccormickrollins1914

Head and neck cancer (HNC) constitute 5% of all reported cancers. Among all, the oral cavity cancer is the most frequent type of HNC which accounts for over half of HNC cases. Mouth cancer ranks the sixth leading cause of cancer-related mortality. Generally, conventional chemotherapy has shown success at decreasing relapse and metastasis rates and improves the overall prognosis. Recently, target therapy and targeted drug delivery systems have been introduced as promising treatments. The elimination of efficiency of current therapeutic strategies due to the spared cancer stem cells that cause chemotherapy resistance, relapse and metastasis. Inefficiency methodologies in the elimination of all cancer cells in the body are a major problem that remained to be resolved before to confront the new cancer therapies. Many studies imply to cancer stem cell markers as important agents for targeted anti-cancer as well as improving chemotherapy efficiencies. The potentials of targeted cancer therapy led us to search for novel markers in the mouth cancer stem cells especially in rare cancers. The aimed of this research was, first a comprehensive critical review of the previous studies on the markers of cancer stem cells in oral cancers including oral squamous cell carcinoma, salivary gland cancers, and to highlight the most common cancer stem cell markers which have potential to be exploited as indicators for the preneoplastic lesion malignancy, oral cancer progression, and/or treatment prognosis. AIMS Improving the environment of the injured area and the preconditioning of mesenchymal stem cells (MSCs) are promising approaches to optimize the therapeutic properties of transplanted MSCs. Herein we investigated the synergistic effects of treadmill exercise and dimethyloxalylglycine (DMOG)-preconditioned stem cells in an Alzheimer's disease (AD) animal model. MATERIALS AND METHODS The MSCs were treated with DMOG for 24 h and transplanted in the AD model intravenously. In addition to cell transplantation, the rats went on treadmill exercise for one month. Memory function, BDNF expression, neurogenesis, apoptosis, and antioxidant capacity were assessed using shuttle box and Morris water maze tasks, ELISA, immunohistochemistry, western blot, and biochemical methods. KEY FINDINGS Transplantation of DMOG-treated cells caused a memory improvement compared to the AD group via an increase in neurogenesis and expression of nestin, Sox-2, and NeuroD. Moreover, the injection of preconditioned cells was more effective in increasing the total antioxidant capacity and the BDNF level and decreasing the MDA and caspase-3 than the non-treated cells. Treadmill exercise improved spatial memory and learning through an increase in BDNF and neurogenesis. Finally, treadmill exercise and transplantation of the treated cells together had the most neuroprotective effects. SIGNIFICANCE It seems that the transplantation of DMOG-treated cells besides exercise may have protective effects in the AD model via an increase in BDNF, antioxidants, and neurogenesis and a decrease in apoptosis. AIMS This study aimed to uncover the underlying mechanisms of METTL1/let-7e miRNA/HMGA2 axis regulated colon cancer (CC) development. MATERIALS AND METHODS Real-Time qPCR was used to detect the expression levels of METTL1 mRNA and let-7e miRNA in clinical specimens and cell lines. Pearson correlation analysis was conducted to analyze the correlation of let-7e miRNA and METTL1 mRNA in cancer tissues. Western Blot was performed to examine protein expressions. Cell proliferation was evaluated by CCK-8 assay and cell mobility was determined by transwell assay. Dual-luciferase reporter gene system was used to validate the binding sites of let-7e miRNA and 3' UTR regions of HMGA2 mRNA. KEY FINDINGS METTL1 and let-7e miRNA were low-expressed in CC tissues and cells compared to their normal counterparts. Overexpression of METTL1 inhibited CC cell proliferation, invasion as well as migration, and promoted cell apoptosis. Further results validated that METTL1 overexpression increased the levels of let-7e miRNA in CC cell lines, and the effects of overexpressed METTL1 on the above cell functions were reversed by knocking down let-7e miRNA. In addition, high mobility group AT-hook 2 (HMGA2) was the downstream target of let-7e miRNA, and overexpressed METTL1 inhibited HMGA2 expressions by upregulating let-7e miRNA in CC cells. Interestingly, the effects of overexpressed METTL1 on CC cell functions were also reversed by upregulating HMGA2. SIGNIFICANCE Overexpression of METTL1 inhibited CC progression by inhibiting HMGA2 through upregulating let-7e miRNA. AIMS Rigosertib (RGS) is a PI3K inhibitor that exerts protective effects against tumor progression and cancer-related inflammation. This study was aimed to explore the regulatory effects of RGS on proliferative, pro-fibrotic and inflammatory factors in DSS- induced colitis mice model. MATERIALS AND METHODS The present study integrates systems and molecular biology approaches to investigate the therapeutic potency of RGS in an experimental model of colitis specifically examining its effects on the PI3K/AKT and NF-κB signaling pathways. Selleck MitoSOX Red KEY FINDINGS Analysis of time-resolved proteome profiling showed that PI3K-AKT inhibitors regulate expression of many proteins in all stages of inflammation, fibrogenesis and extracellular matrix remodeling. Consistent with our in-silico findings, RGS improved colitis disease activity as assessed by changes in body weight, degree of stool consistency, rectal bleeding and prolapse. RGS also reduced oxidative stress markers and colon histopathological score by decreasing inflammatory responses in colon tissues. Moreover, expression of pro-fibrotic and pro-inflammatory factors including Acta 2, Col 1a1, Col 1a2, IL-1β, TNF-α, INF-γ, and MCP-1 were suppressed in the mice treated with RGS compared to the control group. The protective effects of RGS were mediated by inactivation of PI3K/AKT and NF-kB signaling pathways. SIGNIFICANCE This study clearly demonstrates the anti-proliferative, anti-inflammatory and anti-fibrotic effects of RGS in colitis that may have implications for the treatment of colitis and colitis-associated cancer.