Among scaffolds used in tissue engineering, natural biomaterials such as plant-based materials show a crucial role in cellular function due to their biocompatibility and chemical indicators. Because of environmentally friendly behavior and safety, green methods are so important in designing scaffolds. A key bioactive flavonoid of the Epimedium plant, Icariin (ICRN), has a broad range of applications in improving scaffolds as a constant and non-immunogenic material, and in stimulating the cell growth, differentiation of chondrocytes as well as differentiation of embryonic stem cells towards cardiomyocytes. Moreover, fusion of ICRN into the hydrogel scaffolds or chemical crosslinking can enhance the secretion of the collagen matrix and proteoglycan in bone and cartilage tissue engineering. To scrutinize, in various types of cancer cells, ICRN plays a decisive role through increasing cytochrome c secretion, Bax/Bcl2 ratio, poly (ADP-ribose) polymerase as well as caspase stimulations. Surprisingly, ICRN can induce apoptosis, reduce viability and inhibit proliferation of cancer cells, and repress tumorigenesis as well as metastasis. Moreover, cancer cells no longer grow by halting the cell cycle at two checkpoints, G0/G1 and G2/M, through the inhibition of NF-κB by ICRN. Besides, improving nephrotoxicity occurring due to cisplatin and inhibiting multidrug resistance are the other applications of this biomaterial.

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Stem cells are characterized by two fundamental properties; self-renewal and differentiation. Self-renewal is an integration of proliferation control with the maintenance of an undifferentiated state. Self-renewal trait is regulated by a dynamic process between transcription factors, epigenetic control, microRNA regulators, and cell-extrinsic signals from the niche of stem cells. The other feature of stem cells is the capability of differentiation to various cell types.Neural stem cells are able to differentiate to neuron, glial cell, and oligodendrocyte. The process of oligodendrocyte differentiation also is regulated by an interaction between the genetic and epigenetic programs. Recent studies reveal the key role of histone modifications in epigenetic regulation of gene expression during oligodendrocyte development. Moreover, retinoic acid pathway has been shown in stem cell differentiation toward neurons. Conclusion: Detection of signaling cascades and regulatory networks of self-renewal and differentiation of neural stem cells improve new therapeutic methods for neural diseases, such as brain injuries and brain tumors as well as neurodegenerative diseases, like Huntington, Alzheimer, Parkinson, and demyelination diseases, such as multiple sclerosis. Moreover, understanding of these pathways leads to specific and stable differentiation of neural stem cells toward functional oligodendrocyte for alternative therapy.

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The expression of STAT3 in J774A.1 cells confirmed that these cells are M2 macrophage. Moreover, silencing of STAT3 by siRNA delivery using oligofectamine delivery suggests that siRNA delivery using vehicles like nanoliposome could be a useful therapeutic agent in M2 macrophage therapy and its switch to M1 macrophages. This approach could be considered as a novel therapeutic agent for the treatment of all cancers.