Hepatic fibrosis is a physiological response to liver injury that includes a range of cell types. The pathogenesis of hepatic fibrosis currently focuses on hepatic stellate cell (HSC) activation into muscle fiber cells and fibroblasts. Baicalin is a flavone glycoside. It is the glucuronide of baicalein, which is extracted from the dried roots of Scutellaria baicalensis Georgi. Previous work focused on the anti-viral, -inflammatory and -tumor properties of baicalin. However, the potential anti-fibrotic effects and mechanisms of baicalin are not known. The present study demonstrated that baicalin influenced the activation, proliferation, apoptosis, invasion and migration of platelet-derived growth factor-BB-induced activated HSC-T6 cells in a dose-dependent manner. To investigate the anti-fibrotic effect of baicalin, a one-color micro (mi)RNA array and reverse transcription-quantitative polymerase chain reaction analyses were used. Results demonstrated that baicalin increased the expression of the miRNA, miR-3595. In addition, the inhibition of miR-3595 substantially reversed the anti-fibrotic effect of baicalin. The present data also suggested that miR-3595 negatively regulates the long-chain-fatty-acid-CoA ligase 4 (ACSL4). Furthermore, ACSL4 acted in a baicalin-dependent manner to exhibit anti-fibrotic effects. Taken together, it was concluded that baicalin induces miR-3595 expression that modulates the expression levels of ACSL4. To the best of our knowledge, the present study is the first to demonstrate that baicalin induces overexpression of human miR-3595, and subsequently decreases the expression of ACSL4, resulting in an anti-fibrotic effect.
BackgroundEndothelial-to-mesenchymal transition (EMT) and angiogenesis play important roles in colorectal cancer (CRC) development. Connective tissue growth factor (CTGF) has been reported to promote several kinds of cancer progression and miR-218 has been identified as a tumor suppressor miRNA. However, little is known about the function of miR-218 in CRC. Here we investigated the effects of miR-218 on EMT and angiogenesis process in CRC cells. As well, the relation between miR-218 and CTGF was identified. The mechanism of miR-218’s function was illustrated.MethodsCRC cell lines were transfected with miR-218 mimics. Proliferation, migration and angiogenesis were identified by MTT assay, Transwell assay, colony formation assay and tube formation assay. Protein and mRNA expression levels of associated genes were measured by Western blotting and RT-PCR. Dual luciferase assay was used to determine the relation of miR-218 and CTGF.ResultsmiR-218 was down-regulated in CRC cell lines and over expression of miR-218 could significantly inhibit EMT and angiogenesis. CTGF was a direct target of miR-218. Up regulation of CTGF level after miR-218 transfection could sufficiently rescue the suppression effects on EMT and angiogenesis.ConclusionmiR-218 directly targets CTGF and inhibits its expression, leading to suppression on EMT and angiogenesis of CRC cells. miR-218 might be used as potential therapeutic strategy for CRC treatment.
Abstract65 Cu central-transition NMR spectroscopy of the blue copper protein azurin in the reduced Cu(I) state, conducted at 18.8 Tesla and 10 K, gave a strongly second order quadrupole perturbed spectrum, which yielded a 65 Cu quadrupole coupling constant of ±71.2 ± 1 MHz, corresponding to an electric field gradient of ±1.49 atomic units at the copper site, and an asymmetry parameter of approximately 0.2. Quantum chemical calculations employing second order Møller-Plesset perturbation theory and large basis sets successfully reproduced these experimental results. Sensitivity and relaxation times were quite favorable, suggesting that NMR may be a useful probe of the electronic state of copper sites in proteins. Keywords65 Cu NMR; azurin; blue copper protein; nuclear quadrupole couplingCopper is a ubiquitous component of living systems. It fulfills a vital role in many enzymes, particularly redox enzymes. As might be anticipated from the chemistry of the element, the primary redox couple involved in biological redox processes is Cu + /Cu 2+ . However, multinuclear copper centers 1,2 and mixed metal centers 3 give it the ability to participate in multielectron processes. Among its most important redox roles are in cytochrome c oxidase, which was proved to be a copper enzyme by nutritional, enzymological and spectroscopic studies 4 , and which contains three coppers per molecule 5 , two in a dinuclear center. Cytochrome c oxidase acts as the terminal enzyme in the respiratory chain, reducing molecular oxygen in a four-electron process to water. Other copper-containing redox enzymes are tyrosinase 6 and various other oxidases 7 . The copper, zinc superoxide dismutase of mammalian erythrocytes performs the rather different role of eliminating superoxide in an alternating sequence of single-electron oxidation and reduction steps 8 . Some organisms use copper hemocyanins, which contain a binuclear copper site 9 , as oxygen transporters. In addition to these metabolic functions, organisms use copper chaperones 10 to transport the toxic metal. In terms of generalities, it has been noted 11 that copper is usually associated with the metabolism of O 2 or oxides of nitrogen, and copper proteins often also contain organic radicals.CORRESPONDING AUTHOR: gerry@setanta.unl.edu. † Pacific Northwest National Laboratory § University of Nebraska at Lincoln SUPPORTING MATERIALS Supporting materials contain the complete reference 43 and 45 , as well as Tables 5 and 6, which give the optimized coordinates of the model complex bis(imidazole)copper(I)methylsulfide and the quantum region of azurin used in QM/MM calculations. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptCopper sites in proteins have been classified into several types: type-1 12 , type-2 13 , and type-3 1 copper, as well as the dinuclear CuA center 14 . Among the best-studied are the type-1 sites, characterized by a strong absorption in the orange region of the visible spectrum. The blue copper proteins, a class of relatively ...
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