mTOR signalling pathway in stem cell bioactivities and angiogenesis potential.

The mammalian target of rapamycin (mTOR) is a protein kinase that responds to different stimuli such as stresses, starvation and hypoxic conditions. The modulation of this effector can lead to the alteration of cell dynamic growth, proliferation, basal metabolism and other bioactivities. Considering this fact, the mTOR pathway is believed to regulate the diverse functions in several cell lineages. Due to the pleiotropic effects of the mTOR, we here, hypothesize that this effector can also regulate the bioactivity of stem cells in response to external stimuli pathways under physiological and pathological conditions. As a correlation, we aimed to highlight the close relationship between the mTOR signalling axis and the regenerative potential of stem cells in a different milieu. The relevant publications were included in this study using electronic searches of the PubMed database from inception to February 2023. We noted that the mTOR signalling cascade can affect different stem cell bioactivities, especially angiogenesis under physiological and pathological conditions. Modulation of mTOR signalling pathways is thought of as an effective strategy to modulate the angiogenic properties of stem cells.

The effect of chrysin-curcumin-loaded nanofibres on the wound-healing process in male rats.

AIM: The aim of the present study was to produce chrysin-curcumin-loaded PCL-PEG nanofibres by an electrospinning technique and to evaluate the biological activity of the chrysin-curcumin-loaded PCL-PEG fibres for wound healing and its related genes using in vivo methods. MATERIALS AND METHODS: The electrospinning method was carried out for the preparation of the chrysin, curcumin and chrysin-curcumin-loaded PCL-PEG nanofibres with different concentrations. FTIR and SEM were performed to characterize the chemical structures and morphology of the nanofibres. In vitro drug release, as well as in vivo wound-healing studies were investigated in male rats. The expressions of genes related to the wound-healing process were also evaluated by real-time PCR. RESULTS: Our study showed that the chrysin-curcumin-loaded nanofibres have anti-inflammatory properties in several stages of the wound-healing process by affecting the IL-6, MMP-2, TIMP-1, TIMP-2 and iNOS gene expression. Our results demonstrated that the effect of the chrysin-loaded nanofibre, the curcumin-loaded nanofibre and the chrysin-curcumin-loaded nanofibre in the wound-healing process is dose dependent and in accordance with the obtained results in that it might affect the inflammation phase more than the other stages of the wound-healing process. CONCLUSION: We have introduced chrysin-curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.

Effects of Hypoxia on Biology of Human Leukemia T-cell Line (MOLT-4 cells) Co-cultured with Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: One of the most significant problems in the treatment of leukemia is the expansion of resistance to chemotherapeutic agents. Therefore, assessing the drug resistance and especially the drug resistance genes of leukemic cells is important in any treatment. The impact of Mesenchymal Stem Cells (MSCs) and hypoxic condition have been observed in the biological performance of majority of leukemic cells. METHODS: MOLT-4 cells were co-cultured with MSCs in the hypoxic condition induced by Cobalt Chloride (CoCl2) for 6 and 24 hr. Then, apoptosis of cells was analyzed using annexin-V/PI staining and expression of the drug resistance genes including MDR1, MRP, and BCRP along with apoptotic and anti-apoptotic genes, including BAX and BCL2, was evaluated by real-time PCR. RESULTS: The hypoxic condition for MOLT-4 cells co-cultured with MSCs could significantly increase the expression of MDR1 and BCRP genes (p<0.05) which are involved in drug resistance. Also, the results indicated that this condition significantly increases the expression of BCL2 (p<0.05) and reduces the apoptosis in MOLT-4 cells co-cultured with MSCs in the hypoxic condition. CONCLUSION: These effects can demonstrate the important role of hypoxia and MSCs on the biological behavior of Acute Lymphoblastic Leukemia (ALL) cells that may lead to particular treatment outcomes.