Introduction Wound healing is an important and complicated process that involves cell proliferation, migration, angiogenesis, reepithelization, and tissue remodeling as a result of complex interactions between growth factors, extracellular matrix molecules, and cells [1]. Stem cells have emerged as a promising treatment for wounds due to their ability to renew and differentiate themselves. Adult stem cells such as bone marrow-derived mesenchymal stem cells (BMSCs) and adipose-derived mesenchymal stem cells (ASCs) are not hard to obtain due to ethical concerns and availability like embryonic stem cells. BMSCs and ASCs can be easily isolated in adults [2,3]. Mesenchymal stem cells (MSCs), a heterogeneous subset of stromal stem cells, are multipotent adult stem cells that are present in multiple tissues, including the umbilical cord, bone marrow, and fat tissue. They are reproducible and have a high potential for use in different areas [4]. Because of their stromal origin, they are supportive and durable. MSCs have the potential to differentiate into different cell types primarily in connective tissue when provided with appropriate microenvironmental conditions [5]. They have osteogenic, adipogenic, chondrogenic, and myogenic differentiation capacities in in vitro conditions Background/aim: Mesenchymal stem cells (MSCs) are a type of adult stem cell consisting of a heterogeneous subset of stromal stem cells that can be isolated from adult tissues. Folic acid is another important contributor to tissue regeneration and repair, which affects the synthesis of some building block molecules used for wound healing. In this study, we examine the effect of folic acid and MSCderived soluble factors in the wound healing model. Materials and methods: Human umbilical vein endothelial cells (HUVECs) and bone marrow-derived MSCs (BMSCs) were cultured for this study. Cell proliferation analysis was done with xCELLigence RTCA. After 48 h of cultivation, the cell culture medium was collected as MSC conditional medium containing mesenchymal stem cell-derived soluble factors (MDFs). Different concentrations of MDFs (12%, 25%, 50%, 75%, and 100%) were applied to the HUVEC cell line. Folic acid (25, 30, 50, 60, 75, 90, and 100 µM) was tested by application of three different groups (control, 25 µM folic acid, 625 µM folic acid inhibitors) for proliferation on the HUVEC cell line. The combined effects of folic acid and MDFs were tested on the HUVEC cell line with 25 µM folic acid and 50 µM MDFs. All data were statistically analyzed using SPSS 15.0 for Windows. Results: Significant differences were observed between controls and cells treated with folic acid, as well as between controls and both folic acid and MDFs (P < 0.05). Among the treated groups, the fastest wound closure rate was seen in cells treated with both folic acid and MDFs. Conclusion: The results show that both folic acid and MDFs increased the wound healing rate in HUVECs when they were used separately. The strongest benefits were seen in treatment using folic acid and MDFs...

Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% +/- 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled (125/131)I-UNG and (125/131)I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of (125/131)I-UOG were higher than those of (125/131)I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of (125/131)I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I-125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages.

Epigallocatechin gallate (EGCG), is the most abundant and widely studied catechin in green tea (Camellia sinensis Theaceae). The inhibitory effects of EGCG and green tea extract on carcinogenesis in various organs in rodents have now been demonstrated over the past decade. The aim of study was to label EGCG with I-131, to determinate its structure and to evaluate its biodistribution in Wistar rats. Radiolabeling was carried out by direct electrophilic iodination method (iodogen) and yield was determined by radio thin layer chromatography (RTLC). Radiolabelling yield is determined as 89 ± 1.0%. Besides, determination of structure of iodinated molecule, serum stability, and partition coefficient experiments was performed. The structure analysis of synthesized cold 127 I-EGCG complex was assessed with LC-MS-MS and 1 H-NMR. 1 H-NMR and LC-MS-MS results of iodinated EGCG ( 127 I-EGCG) show that oxidize iodine reacts electrophilic with aromatic ring. Serum stability results showed that in vitro stability of 131 I-EGCG was quite high. It is observed that labeling percentage decreased 83 ± 2% at 24th, Partition coefficient results show that the partition coefficient of EGCG was calculated as theoretical partition coefficient = 2.04 ± 0.42 and the experimental partition coefficient of 131 I-EGCG was found as 1.46 ± 0.2. The biodistribution data shown that the maximum uptake of the radioiodinated EGCG was seen in lung and pancreas at 30 min. The blocking assay results indicated that the uptake of 131 I-EGCG in lung was not significantly change (0.25, 0.23, and 0.22%ID/g at 30, 60, and 150 min, respectively). Biodistribution data showed no significant uptake in a specific organ of the rat. Hence radiolabeled EGCG is seen in some organs (lung, liver, pancreas, kidney, etc.).

Objectives:Neuroblastoma is an extracranial solid tumor of early childhood that has a hypoxic environment. VEGF and HIFs molecules play a role in adaptation to this microenvironment. Hypoxic microenvironment leads to poor prognosis and inadequate treatment of neuroblastoma. Metformin has been shown to inhibit tumor growth, might be a potential chemotherapeutic agent. The anti-cancer activity of Metformin on SH-SY5Y cells are not fully elucidated. The aim of this study is to determine the anti-cancer effect of Metformin on SH-SY5Y cells and to elucidate its molecular action mechanism in hypoxia/normoxia.Patients and Methods:SH-SY5Y cells were exposed to increasing doses of Metformin. The viability of SH-SY5Y cells was evaluated using the real time xCELLigence RTCA system. Migration of SH-SY5Y cells was determined using wound healing. The effect of metformin on mRNA and protein expression levels was evaluated using Real-time PCR and Western Blot, respectively.Results:Metformin was observed to significantly reduce the viability of SH-SY5Y cells. Metformin treatment reduced migration of SH-SY5Y cells. In addition, Metformin treatment significantly reduced mRNA expression of HIF-1α, PDK-1 and VEGF-A in SH-SY5Y cells under normoxia and hypoxia. In hypoxia condition, protein expression of HIF-1α and VEGF-A decreased after Metformin administration on SH-SY5Y cells. Protein expression of PDK-1 was observed to decrease in both normoxia and hypoxia conditions on SH-SY5Y cells. Conclusion:In this study, the anti-cancer effect of Metformin on SH-SY5Y cells was determined. Metformin has been observed as inhibitor of migration in SH-SY5Y. Metformin treatment has been shown to reduce gene and protein levels of HIF-1α and target molecules in neuroblastoma cells.

trying to increase the success of the treatment by reducing the risk of clonal selection of tumor cells. In combination therapy regimens, targeted therapies provide specificity to inhibit or alter the functions of ABSTRACT Purpose: Cancer cells promote lactate formation via pyruvate rather than oxidative phosphorylation by programming their metabolism to maintain proliferation under the Warburg effect. It has shown that the altered metabolic phenotype with activation of lactate dehydrogenase-A in the cancer cell may affect survival, chemotherapy resistance, and metastasis. In this direction, studies are focusing on reprogramming cancer metabolism and increase the effectiveness of chemotherapy. In this study, the main aim was to target the Warburg phenotype via the inhibition of lactate dehydrogenase with the combination of sodium oxamate and current colorectal cancer treatment options such as 5-fluorouracil and irinotecan. Methods:The effect of chemotherapeutics on the cellular behavior was evaluated by real-time cytotoxicity and migration analysis systems, and metabolic phenotype was assessed by measuring lactate, lactate dehydrogenase expression, and reactive oxygen species levels.Results: According to the results, the viability and migration of colorectal cancer cells were significantly decreased with the combination of chemotherapeutics and sodium oxamate which decreases lactate levels. Conclusion:As a result, the combination of sodium oxamate with chemotherapeutics hinders the cancer cell viability and migration by changing metabolic phenotype with decreased lactate.