Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells
by Alyssa
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Background: inhibits vascularization of bone tissue engineering strategies are not enough to reconstruct large bone defects. Delivery prolyl hydroxylase inhibitor (restricted) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by imitating the stabilization of hypoxia hypoxia-inducible factor-1 alpha (HIF-1α). The study assessed the two is limited to: dimethyloxalylglycine (DMOG) and baicalein for their effect on human adipose tissue-derived mesenchymal stem / stromal cells (AT-MSCs).
Method: Isolated AT-MSCs were marked and treated is limited to cell proliferation response rate. Immunostaining and Western-spotting duty to verify the stabilization of HIF-1α response. concentration that is optimized for long-term treatment were tested for their effect on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs.
the level of gene expression is evaluated for alkaline phosphatase (Alpl), bone morphogenetic protein 2 (BMP2), dwarf related to transcription factor 2 (Runx2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). Additionally, genes associated stemness-Kruppel-like factor 4 (KLF 4 ), Nanog homeobox (NANOG), and octamer < / em> – bind transcription factor 4 (OCT 4 ) rated.
Results: The restricted stabilized HIF-1α in a dose-dependent manner and showed a clear dose and time-dependent antiproliferative effect. At a dose of maintaining proliferation, reduced baicalein DMOG and osteogenic induction effect on the expression of Runx2, Alpl, and COL1A1, and is able to suppress the formation of a mineral matrix. Pressed osteogenic response of AT-MSCs accompanied by upregulation of genes associated with stemness.
Conclusion: This is restricted significantly reduced osteogenic differentiation of AT-MSCs and genes associated with stemness somewhat regulated. This restricted proangiogenic potential must be weighed against the long-term of their direct inhibitory effect on osteogenic differentiation of AT-MSCs.
Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells
A three-gene signature may predict prognosis in patients with acute myeloid leukemia Identification of an effective signature is crucial for predicting the prognosis of acute myeloid leukemia (AML).
The investigation aims to identify new signature for AML predictive prognostic using the expression of three genes ( octamer – bind transcription factor 4 (OCT 4 ), POU domain type 5 transcription factor 1B (POU5F1B) and cell-specific B- murine leukemia integration of virus Moloney site-1 pseudogene 1 (BMI1P1), the expression of genes derived from our previous study. Only specimens in which three genes all expressed were included in this study.
A signature three genes are constructed by Cox multivariate regression for the patients were divided be a high-risk group and low-risk Receiver operating characteristic (ROC) analysis of three-gene signature (area under the ROC curve (AUC) = 0.901, 95% CI :. 0.821- 0.981, P <0.001) indicates that it is a signature more valuable to differentiate between patients and controls from one of the three genes, in addition, cell white blood-cells (leukocytes, P = 0.00 4 ), pl atelets (PLTS, P = 0.017), the percentage of blasts in the bone marrow (BM) (P = 0.011) and complete remission (CR, P = 0.027) had a significant difference between the two groups.
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Furthermore, the high-risk groups of leukemia-free survival shorter (LFS) and overall survival (OS) of the low-risk group (P = 0.026; P = 0.006), and the signature of the three genes are prognostic a factor . three gene signatures for predicting prognosis in AML may serve as a prognostic biomarker.
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