Graphene consists of two-dimensional sp2-bonded carbon sheets, a single or a few layers thick, which has attracted considerable interest in recent years due to its good conductivity and biocompatibility. Three-dimensional graphene foam (3DG) has been demonstrated to be a robust scaffold for culturing neural stem cells (NSCs) in vitro that not only supports NSCs growth, but also maintains cells in a more active proliferative state than 2D graphene films and ordinary glass. In addition, 3DG can enhance NSCs differentiation into astrocytes and especially neurons. However, the underlying mechanisms behind 3DG's effects are still poorly understood. Metabolism is the fundamental characteristic of life and provides substances for building and powering the cell. Metabolic activity is tightly tied with the proliferation, differentiation, and self-renewal of stem cells. This study focused on the metabolic reconfiguration of stem cells induced by culturing on 3DG. This study established the correlation between metabolic reconfiguration metabolomics with NSCs cell proliferation rate on different scaffold. Several metabolic processes have been uncovered in association with the proliferation change of NSCs. Especially, culturing on 3DG triggered pathways that increased amino acid incorporation and enhanced glucose metabolism. These data suggested a potential association between graphene and pathways involved in Parkinson's disease. Our work provides a very useful starting point for further studies of NSC fate determination on 3DG.
Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4+ and CD8+ T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5–5 μg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM–receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.
Induction of endogenous cardiomyocyte (CM) proliferation is one of the key strategies for heart regeneration. Increasing evidence points to the potential role of microRNAs (miRNAs) in the regulation of CM proliferation. Here, we used human embryonic stem cell (hESC)-derived CMs (hESC-CMs) as a tool to identify miRNAs that promote CM proliferation. We profiled miRNA expression at an early stage of CM differentiation and identified a list of highly expressed miRNAs. Among these miRNAs, miR-25 was enriched in early-stage hESC-CMs, but its expression decreased over time. Overexpression of miR-25 promoted CM proliferation. RNA sequencing (RNA-seq) analysis revealed that genes related to cell-cycle signal were strongly influenced by miR-25 overexpression. We further showed that miR-25 promoted CM proliferation by targeting FBXW7. Finally, the function of miR-25 in the regulation of CM proliferation was demonstrated in zebrafish. Our study suggested that miR-25 is a promising molecule for heart regeneration.
Chemotherapy is one of the most commonly used treatments for patients with advanced colon cancer, yet the toxicity of chemotherapy agents, such as 5-fluorouracil (5-FU), limits the effectiveness of chemotherapy. Ginsenoside Rg3 (Rg3) is an active ingredient isolated from ginseng. Rg3 has been shown to display anticancer effects on a variety of malignancies. Yet, whether Rg3 synergizes the effect of 5-FU to inhibit the growth of human colon cancer remains unknown. The present study was designed to ascertain whether Rg3 is able to enhance the anti-colon cancer effect of 5-FU. The results revealed that combined treatment of Rg3 and 5-FU significantly enhanced the inhibition of the proliferation, colony formation, invasion and migration of human colon cancer cells (SW620 and LOVO) in vitro. We also found that combined treatment of Rg3 and 5-FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. In addition, the PI3K/AKT signaling pathway in colon cancer cells was suppressed by Rg3 and 5-FU. In vivo, Rg3 synergized the effect of 5-FU to inhibit the growth of human colon cancer xenografts in nude mice. Similarly, combined treatment of Rg3 and 5-FU altered the expression of colon cancer protein in vivo and in vitro. Collectively, the present study demonstrated that ginsenoside Rg3 enhances the anticancer effect of 5-FU in colon cancer cells via the PI3K/AKT pathway.
Extracellular Vesicle (EV) is a compilation of secreted vesicles, including micro vesicles, large oncosomes, and exosomes. It can be used in non-invasive diagnosis. MicroRNAs (miRNAs) processed by exosomes can be detected by liquid biopsy. To objectively evaluate the discriminative ability of miRNAs from whole plasma, EV and EV-free plasma, we analyzed the miRNA expression profiles in whole plasma, EV and EV-free plasma of 10 lung adenocarcinoma and 9 granuloma patients. With Monte-Carlo feature selection method, the top discriminative miRNAs in whole plasma, EV and EV-free plasma were identified, and they were quite different. Using the Repeated Incremental Pruning to Produce Error Reduction (RIPPER) method, we learned the classification rules: in whole plasma, granuloma patients did not express hsa-miR-223-3p while the lung adenocarcinoma patients expressed hsa-miR-223-3p; in EV, the hsa-miR-23b-3p was highly expressed in granuloma patients but not lung adenocarcinoma patients; in EV-free plasma, hsa-miR-376a-3p was expressed in granuloma patients but barely expressed in lung adenocarcinoma patients. For prediction performance, whole plasma had the highest weighted accuracy and EV outperformed EV-free plasma. Our results suggested that EV can be used as lung cancer biomarker. However, since it is less stable and not easy to detect, there are still technological difficulties to overcome.
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