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BACKGROUND: A growing number of studies has indicated that the expression of Breast Cancer Susceptibility Genes 1 (BRCA1) and BRCA2 contribute to the resistance to DNA-damaging chemotherapies. Tamoxifen induces tumor cell death by suppressing estrogen receptor (ER) signaling and inducing DNA damage, and BRCA1 upregulation causes Tamoxifen chemoresistance in breast cancer cells. Consequently, this research study aimed to investigate the possible therapeutic effect of Human Umbilical Cord Mesenchymal Stem Cells Conditioned Medium (UCMSCs-CM) on sensitizing breast cancer cells to Tamoxifen by regulating BRCA1 and BRCA2 expression in vivo. METHODS: Forty female mice, 4-8 weeks old, with weight of 150 g, were used for this study. Mouse 4T1 breast tumor models were established and then treated with UCMSCs-CM and Tamoxifen alone or in combination. After 10 days, the tumor masses were collected and the expression levels of BRCA1 and BRCA2 were evaluated using qRT-PCR assay. RESULTS: The results obtained from qRT-PCR assay illustrated that UCMSCs-CM, either alone or in combination with Tamoxifen, significantly downregulated the mRNA expression levels of BRCA1 in breast cancer mouse models. However, both UCMSCs-CM and Tamoxifen indicated no statistically significant impact on BRCA2 mRNA expression compared to controls. CONCLUSION: Our findings evidenced that UCMSCs-CM could be considered as a potential therapeutic option to modulate Tamoxifen chemosensitivity by regulating BRCA1 in breast cancer.

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Epigenetic variations can play remarkable roles in different normal and abnormal situations. Such variations have been shown to have a direct role in the pathogenesis of various diseases either through inhibition of tumor suppressor genes or increasing the expression of oncogenes. Enzymes involving in epigenetic machinery are the main actors in tuning the epigenetic-based controls on gene expressions. Aberrant expression of these enzymes can trigger a big chaos in the cellular gene expression networks and finally lead to cancer progression. This situation has been shown in different types of leukemia, where high or low levels of an epigenetic enzyme are partly or highly responsible for involvement or progression of a disease. DNA hypermethylation, different histone modifications, and aberrant miRNA expressions are three main epigenetic variations, which have been shown to play a role in leukemia progression. Epigenetic based treatments now are considered as novel and effective therapies in order to decrease the abnormal epigenetic modifications in patient cells. Different epigenetic-based approaches have been developed and tested to inhibit or reverse the unusual expression of epigenetic agents in leukemia. The reciprocal behavior of miRNAs in the regulation of epigenetic modifiers, while being regulated by them, unlocks a new opportunity in order to design some epigenetic-based miRNAs able to silence or sensitize these effectors in leukemia.

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The interaction between glioma cells and the surrounding microenvironment plays a key role in tumor invasion and infiltration ability. Recent studies reported the importance of glioma-derived microvesicles in the interaction of the tumor and the surrounding environment. The purpose of this study was to scrutinize the role of glioma-derived microvesicles in the interaction between tumor and normal astrocytes, which are the most abundant non-neoplastic cells in the tumor microenvironment (TME). To this end, we examined the effect of C6 tumor cell-derived microvesicles in the activation of normal rat astrocytes. The results showed that exposing normal astrocytes to C6MVs increase the expression of the glial fibrillary acidic protein (GFAP), and activate normal astrocytes. In addition, incubation of normal astrocytes with C6MVs affects the expression of genes involved in tumor invasion and growth in these cells. Our findings suggest that C6 tumor cells through the secretion of microvesicles (MVs) can alter the phenotype of surrounding astrocytes as well as through the changes in the expression of the genes involved in extracellular matrix remodeling can predispose their invasion and growth.

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BACK GROUND: Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. METHODS: First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. RESULTS: The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. CONCLUSION: The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.

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The progression of nanotechnology provides opportunities to manipulate synthetic and natural materials to mimic the natural structure for tissue engineering applications. The electrospinning technique applies electrostatic principle to fabricate electrospun nanofibers. Nanofiber scaffolds are precisely similar to the native extracellular matrix (ECM) and support cell proliferation, adhesion, tendency to preserve their phenotypic shape and directed growth according to the nanofiber direction. This study reviewed both the natural and synthetic type of nanofibers and described the different properties used to trigger certain process in the tissue development. Also, the potential applications of electrospun scaffolds for regenerative medicine were summarized.

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OBJECTIVE: The role of miR-16/15b/195 and complementary compounds in the commitment of mesenchymal stem cells (MSCs) to different lineages is unknown. The aim of this work was to investigate the effect of ketorolac and triamcinolone acetonide on adipogenic and hepatogenic processes, respectively. Also, miR-16/15 and miR-195 expression levels were evaluated under different induction conditions. METHODS: MSCs were isolated, expanded and directed using adipogenesis medium or medium supplemented with ketorolac, and also subjected to hepatogenic differentiation using a cocktail of hepatocyte growth factor (HGF) and Oncostatin M (OSM) either with or without triamcinolone acetonide. Periodic acid-Schiff (PAS) staining, Oil red O staining, albumin and adiponectin protein secretion were evaluated. MiR-16 family expression level was assessed using qRT-PCR in four induced groups as compared to non-induced cells. RESULTS: The expression levels of miR-16 and miR-15 increased significantly from adipose derived stem cells to adipocytes (p<0.01). Positive stimulatory effects of ketorolac and triamcinolone on adipogenic and hepatogenic induction, respectively, were observed. Ketorolac stimulated upregulation of miR-16/15b in the adipogenic induced stem cells. Interestingly, triamcinolone caused upregulation of miR-15b and miR-195 in hepatic commitment. CONCLUSIONS: Two highly effective stimulators were identified. Ketorolac is similar to indomethacin and affects adipogenic differentiation. Triamcinolone is involved in hepatogenic commitment of stem cells like differentiation process of macrophages, adipocytes and osteocytes. The alteration of miR-16 family members' expression indicates that this family may play a possible role in directing stem cell fate.

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Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches that modulate stem cells outcomes in response to diverse extracellular signals. Numerous scientific evidences implicating miRNAs in major signal transduction pathways highlight new crosstalks of cellular processes. Aberrant signaling pathways and miRNAs levels result in developmental defects and diverse human pathologies. This review discusses the crosstalk between the components of main signaling networks and the miRNA machinery, which plays a role in the context of stem cells development and provides a set of examples to illustrate the extensive relevance of potential novel therapeutic targets.

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Dendrimers are nano-sized, radially symmetric molecules with well-defined, homogeneous, and monodisperse structure that has a typically symmetric core, an inner shell, and an outer shell. Their three traditional macromolecular architectural classes are broadly recognized to generate rather polydisperse products of different molecular weights. A variety of dendrimers exist, and each has biological properties such as polyvalency, self-assembling, electrostatic interactions, chemical stability, low cytotoxicity, and solubility. These varied characteristics make dendrimers a good choice in the medical field, and this review covers their diverse applications.