Highlights d Mechanical tension-induced Yap activation triggers hepatocyte dedifferentiation d Confinement of cell spreading is sufficient to inhibit hepatocyte dedifferentiation d A chemical cocktail, LBDXL, maintains hepatocyte functions by targeting stress fibers d LBDXL hepatocytes resemble primary hepatocytes in gene expression and functions

Utilizing novel approaches for the green synthesis of metal nanoparticles are of great importance. Therefore, we reported biogenic synthesis of silver nanoparticles (AgNPs) using extracts of Leptolyngbya strain JSC-1, and their significant applications against pathogenic bacteria and cancerous HeLa cell line. The biofabricated AgNPs were characterized by UV-visible spectroscopy, FTIR, SEM, TEM, DLS and zeta-potential. The as prepared AgNPs were assessed for inhibition of bacterial growth and induction of apoptosis in HeLa cells by different doses of AgNPs was evaluated. UV-visible spectroscopy and FTIR of AgNPs demonstrated the surface plasmon resonance at 413 nm and interaction among extract and nanoparticles, respectively. Electron microscopy revealed the morphology and DLS demonstrated size distribution of the particles (10-100 nm). Zeta potential values were between -47 and 0 mV, indicating stability of the particles. Proliferation of HeLa cells was significantly inhibited and severe cytotoxicity with higher intracellular uptake were observed after applying high concentration of AgNPs. Efficient inhibition zones (17 ± 2 and 21 ± 2 mm) were produced at maximum concentration (100 µl from 1 mg ml stock of AgNPs) for Staphylococcus aureus and Escherichia coli, respectively. These findings reveal that the biofabricated AgNPs possess strong antibacterial activity and ability to induce apoptosis in cancer cell line (HeLa).

Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271 +/high cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. CD271 +/high cells could accumulate more CONPs than CD271 −/low through clathrin-mediated endocytosis. In addition, lower dosage of CONPs exhibited good anti-melanoma effect by decreasing the cell viability, stemness and tumorigenesis of A375 and WM266-4 cells through reducing the expression of SOX10, MITF, CD271 and genes in MAPK pathway involved in tumor progression. Finally, CONPs obviously suppressed the growth of human melanoma in tumor-bearing nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice, accompanied with tumors structural necrosis and fibrosis remarkably and decreased expression of CD271, SOX10 and MITF. These results above proved the effectiveness of CONPs in inhibiting melanoma progress through multiple pathways, especially through targeting melanoma stem cells.

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