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OBJECTIVES: Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stromal cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) development and metastasis is controversial. Strong evidence demonstrated that conditioned medium (CM) obtained from MSCs regulates main cellular functions such as proliferation, differentiation, migration, and communication due to its cell secretomes. This study was designed to determine the inhibitory effect of dental pulp stem cells (DPSC) and its extracted conditioned medium (DPSC-CM) in CRC progression. MATERIALS AND METHODS: The inhibitory effects of DPSC-CM on growth, apoptosis, and migration of CRC cells were evaluated by resazurin, flow cytometry of propidium iodide (PI) stained cells, and wound closure assay, respectively. Western blotting detected the expression of MAPKinase and apoptotic proteins. Also, the homing ability of DPSCs and the invasion ability of CRC cells under indirect co-culture were assayed by the Boyden chamber assay. RESULTS: DPSC-CM reduced the viability and induced the apoptosis of CRC cells significantly. Western blot analysis confirmed the increase in cytochrome C, phospho-JNK/SAPK to JNK/SAPK ratio, cleaved-caspase 8 and 3 in treated CRC cells with DPSC-CM, and decrease in phospho-ERK (P44/42 MAPK) to ERK (P44/42 MAPK) ratio, which are involved in induction of apoptosis and growth inhibition of cancer cells with minimal change in normal cells. Also, DPSCs could migrate (homing ability) to Caco2 and SW48 cells significantly. CONCLUSION: To sum up, DPSC-CM had significant apoptotic and growth inhibitory effects on the CRC cells through the MAPKinase and apoptosis signaling pathways.
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BACKGROUND: One of the adverse effects of phenytoin (diphenylhydantoin, DPH) is enlargement of facial features. Although there are some reports on anabolic action of phenytoin on bone cells, the osteogenic potential of DPH on mesenchymal stem cells has not been studied. The purpose of this study was to evaluate the osteogenic potential of DPH on dental pulp stem cells (DPSCs). METHODS: Human DPSCs were isolated and characterized by flow cytometry; presence of CD29 and CD44 and absence of CD34 and CD45 were performed to confirm the mesenchymal stem cells. Isolated DPSCs were differentiated either in conventional osteogenic medium with Dexamethasone or medium containing different concentration of phenytoin (12.5, 25, 100, and 200 µM). The osteogenic differentiation evaluated by performing western blot test for Runt-related transcription factor 2 (RUNX2), osteopontin and alkaline phosphatase (ALP) also alizarin red S staining to measure the mineralization of cells. RESULTS: Our results showed morphological changes and mineralization of DPSCs by using DPH were comparable with dexamethasone. Moreover, western blot results of DPH group showed significant increase of ALP, RUNX2 and osteopontin (OSP) in comparison with control. CONCLUSION: The data of present study showed the osteogenic activity of phenytoin, considering as an alternative of dexamethasone for inducing osteogenic differentiation of dental pulp stem cells.
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The aim of this study was to define the electrocardiogram (ECG) changes following the moderate to severe CO intoxication in rats, and also evaluating the effect of erythropoietin (EPO) on observed cardiac disturbances. The growing literature on erythropoietin effect on cardiac ischemia led us to question its effect on cardiotoxicity due to the carbon monoxide poisoning. Wistar rats were exposed to three different concentrations of CO (250 PPM, 1000 PPM or 3000 PPM). EPO was administrated (5000 IU/Kg, intraperitoneal injection) at the end of CO exposure and then the animals were re-oxygenated with ambient air. Subsequently ECG recording, heart rate and carboxyhemoglobin values were evaluated. ECG changes following the CO intoxication included ST segment elevation and depression, T wave inversion and first-degree AV block. Ischemic ECG changes reduced significantly in EPO-treated animals. In the present study, for the first time, EPO was investigated for the management of cardiac complications due to the CO poisoning. Our results showed that EPO could inhibit ischemic changes of ECG after the CO poisoning.
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A series of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1,3,4-thiadiazoles (5a-d and 6a-j) were synthesized and evaluated against Leishmania major promastigotes using (3)H-thymidine incorporation. Most of the compounds showed activity better than the reference drug sodium stibogluconate (Pentostam). The most active compound was 6c (IC(50)=0.1 microM).
