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Different cellular and molecular mechanisms contribute to chondrocyte and osteocyte development. Although vital roles of the mothers against decapentaplegic homolog 4 (also called 'SMAD4') have been discussed in different cancers and stem cell‐related studies, there are a few reviews summarizing the roles of this protein in the skeletal development and bone homeostasis. In order to fill this gap, we discuss the critical roles of SMAD4 in the skeletal development. To this end, we review the different signalling pathways and also how SMAD4 defines stem cell features. We also elaborate how the epigenetic factors—ie DNA methylation, histone modifications and noncoding RNAs—make a contribution to the chondrocyte and osteocyte development. To better grasp the important roles of SMAD4 in the cartilage and bone development, we also review the genotype‐phenotype correlation in animal models. This review helps us to understand the importance of the SMAD4 in the chondrocyte and bone development and the potential applications for therapeutic goals. [ABSTRACT FROM AUTHOR]

Background: The Islets of Langerhans include Alpha, Beta, Delta, and Epsilon cells whose secret hormones play important roles in glucose metabolism as well as some physiological processes in our own body. Method: In this study, we selected a microarray row data of transplanted pancreatic Islets from Gene Expression Omnibus (GEO) database. The row data of 10 individual samples was analyzed with R programing software. Top expressed genes in human pancreatic islets were chosen and the gene stable IDs were returned to gene names and descriptions by BioMart tools. The selected genes were categorized into biological processes by Protein Analysis Through Evolutionary Relationships (PANTHER) online database. Also, sub-cellular localization of their proteins was investigated by the protein atlas database. Results: The results showed that the quality controls of all 10 individual samples of microarray chips such as signal intensity and uniformity of the images were passed. From 336 genes, 284 proteins were classified by PANTHER online database. They are categorized into "Translational proteins", "Metabolism enzymes", and "Protein modifying enzymes" biological processes, respectively. Conclusion: In this study, we presented 500 top-ranked expressed genes in human pancreatic islets. We also represented calcification and sub-cellular localization of these high expressed genes in separate supplementary files. Research data can be used for pancreatic research as well as potential drug design for type I diabetes or pancreatic cancers. [ABSTRACT FROM AUTHOR]

Background: During research on lymphoma and its malignancies, scientists have traced the role of the angiogenesis index in patient survival. Epstein-Barr virus (EBV) is a human tumor-causing virus that targets B lymphocytes and causes persistent infection. This virus is also associated with malignancies, such as Burkitt's lymphoma. Using herbal medicines to treat cancer and angiogenesis has been considered, due to the side effects of chemical drugs. This experimentation aimed to research the antiviral impact of nano-curcumin on the Daudi cell line (which belongs to Burkitt's lymphoma) and to evaluate the expression of the vascular endothelial growth factor (VEGF) gene. Materials and Methods: The cytotoxicity of nano curcumin, curcumin, and dendrosome on Daudi cells and normal human lymphocytes was evaluated using an MTT assay. Cellular apoptosis was assessed by Annexin / PI flow cytometry. The VEGF angiogenesis gene expression was performed by real-time PCR. Results: The 50% cytotoxic concentration (CC50) was determined 30 µg/ml for dendrosomal nano-curcumin, 50 µg/ml for curcumin, and 987 µg/ml for dendrosome in the Daudi cell line. Dendrosomal nano curcumin (DNC) caused time and dose-dependent death in Daudi cancer cells compared to curcumin. Dendrosome did not show toxicity on control cells. The results of Flow cytometry are constant with the results of the MTT test. The data obtained from the real-time PCR showed a significant decrease in the expression of the VEGF gene (P <0.01). Conclusion: The dendrosomal nano curcumin is involved in angiogenesis by reducing the expression of the VEGF gene, and can be a good candidate as a supplement drug in the chemotherapy treatment of Burkitt's lymphoma. [ABSTRACT FROM AUTHOR]

Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression of Bax, Bcl-2, mTOR, hTERT, PUMA, p53 and p21 genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated. [ABSTRACT FROM AUTHOR]