Background/Aims: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-β1). Methods: Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFβ receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. Results: We found that EndMT of EPCs induced by TGF-β1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-β1-induced EndMT by directly targeting TGFBR2 and SMAD3. Conclusions: MALAT1 modulates TGF-β1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-β1-induced EndMT.
Background/Aims: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. Methods: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. Results: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). Conclusion: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.
A poly(propylene carbonate) (PPC)-based sandwichlike composite solid polymer electrolyte (SE) was designed and applied to solid-state lithium ion batteries at 25 °C. The sandwichlike structure of the composite SE was composed of three parts. A polypropylene separator was used as a support membrane to enhance the strength of the SE membrane. Succinonitrile in the PPC-based SE was used to increase the ionic conductivity. Pure PPC as a buffer layer was closed to the lithium anode, which could improve the interface compatibility, Coulombic efficiency, and cycle life of batteries. The sandwich-like composite SE exhibited good comprehensive properties such as a high ion transference number (0.65), sufficient ionic conductivity (2.18 × 10 −4 S cm −1 and 5.77 × 10 −4 S cm −1 at 25 and 55 °C, respectively), and outstanding electrochemical stability at ambient temperature. Furthermore, a Li/LiFePO 4 cell with the sandwich-like composite SE delivered a discharge capacity close to 140 mA h g −1 (0.1 C) at 25 °C. The results suggested that a sandwich-like PPC-based electrolyte is a promising SE for solid-state batteries.
Dysfunction of endothelial progenitor cells (EPCs) is a key factor in vascular complications of diabetes mellitus. Although the roles of microRNAs and circular RNAs in regulating cell functions have been thoroughly studied, their role in regulating autophagy and apoptosis of EPCs remains to be elucidated. This study investigated the roles of mir-20a-5p and its predicted target circ-ADAM9 in EPCs treated with high glucose (30 mM) and in a diabetic mouse hind limb ischemia model. It is found that Mir-20a-5p inhibited autophagy and apoptosis of EPCs induced by high-concentration glucose. Further, mir-20a-5p could inhibit the expression of PTEN and ATG7 in EPCs, and promote the phosphorylation of AKT and mTOR proteins under high-glucose condition. Investigation of the underlying mechanism revealed that circ-ADAM9, as a miRNA sponges of mir-20a-5p, promoted autophagy and apoptosis of EPCs induced by high-concentration glucose. Circ-ADAM9 upregulated PTEN and ATG7 in interaction with mir-20a-5p, and inhibited the phosphorylation of AKT and mTOR to aggravate autophagy and apoptosis of EPCs under high glucose. In addition, silencing of circ-ADAM9 increased microvessel formation in the hind limbs of diabetic mice. Our findings disclose a novel autophagy/apoptosis-regulatory pathway that is composed of mir-20a-5p, circ-ADAM9, PTEN, and ATG7. Circ-ADAM9 is a potential novel target for regulating the function of diabetic EPCs and angiogenesis.
For the high-efficiency PM6:Y6 binary system, there is still space for narrowing the lowest unoccupied molecular orbital (LUMO) level offset (0.36 eV) between PM6 and Y6 to further mitigate energy...
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