62 research outputs found

    15-Deoxy-Δ 12,14

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    It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2 on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2 on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that in vivo, 15d-PGJ2 administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and, in vitro, 15d-PGJ2 suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2 was blocked by reactive oxygen species (ROS) inhibitor, but not PPARγ antagonist, and action of 15d-PGJ2 was not reproduced by PPARγ synthetic ligands. In addition, 15d-PGJ2 triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2 plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis

    Epimorphin Regulates Bile Duct Formation via Effects on Mitosis Orientation in Rat Liver Epithelial Stem-Like Cells

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    Understanding how hepatic precursor cells can generate differentiated bile ducts is crucial for studies on epithelial morphogenesis and for development of cell therapies for hepatobiliary diseases. Epimorphin (EPM) is a key morphogen for duct morphogenesis in various epithelial organs. The role of EPM in bile duct formation (DF) from hepatic precursor cells, however, is not known. To address this issue, we used WB-F344 rat epithelial stem-like cells as model for bile duct formation. A micropattern and a uniaxial static stretch device was used to investigate the effects of EPM and stress fiber bundles on the mitosis orientation (MO) of WB cells. Immunohistochemistry of liver tissue sections demonstrated high EPM expression around bile ducts in vivo. In vitro, recombinant EPM selectively induced DF through upregulation of CK19 expression and suppression of HNF3α and HNF6, with no effects on other hepatocytic genes investigated. Our data provide evidence that EPM guides MO of WB-F344 cells via effects on stress fiber bundles and focal adhesion assembly, as supported by blockade EPM, β1 integrin, and F-actin assembly. These blockers can also inhibit EPM-induced DF. These results demonstrate a new biophysical action of EPM in bile duct formation, during which determination of MO plays a crucial role

    Urinary Metabolomics Study of Patients with Gout Using Gas Chromatography-Mass Spectrometry

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    Objectives. Gout is a common type of inflammatory arthritis. The aim of this study was to detect urinary metabolic changes in gout patients which may contribute to understanding the pathological mechanism of gout and discovering potential metabolite markers. Methods. Urine samples from 35 gout patients and 29 healthy volunteers were analyzed by gas chromatography–mass spectrometry (GC–MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between two groups, and the variable importance for projection (VIP) values and Student’s t-test results were combined to define the significant metabolic changes caused by gout. Further, binary logistic regression analysis was performed to establish a model to distinguish gout patients from healthy people, and receiver operating characteristic (ROC) curve was made to evaluate the potential for diagnosis of gout. Result. A total of 30 characteristic metabolites were significantly different between gout patients and controls, mainly including amino acids, carbohydrates, organic acids, and their derivatives, associated with perturbations in purine nucleotide synthesis, amino acid metabolism, purine metabolism, lipid metabolism, carbohydrate metabolism, and tricarboxylic acid cycle. Binary logistic regression and ROC curve analysis showed the combination of urate and isoxanthopterin can effectively discriminate the gout patients from controls with the area under the curve (AUC) of 0.879. Conclusion. Thus, the urinary metabolomics study is an efficient tool for a better understanding of the metabolic changes of gout, which may support the clinical diagnosis and pathological mechanism study of gout

    Changes in Fruit Quality and Sugar Components of Wild <i>Actinidia eriantha</i> of Different Varieties (Lines) at the Ripening Stage

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    In order to better understand the changes in fruit quality and soluble sugar components in wild Actinidia eriantha at the soft ripening stage, this study explored the fruit quality indexes, soluble sugar components, sucrose metabolism-related enzyme activities and the expression of sucrose metabolism-related enzyme genes in wild A. eriantha germplasm resources. The results showed that the fruit quality of wild A. eriantha at the soft ripening stage was quite different, and the coefficient of variation of fructose content was the largest, followed by sucrose and glucose. Principal component analysis and systematic clustering analysis showed that the comprehensive performance of fruit quality indexes of M28 and M10 was the most prominent. The accumulation and composition of soluble sugar components in different wild A. eriantha varieties (lines) were not consistent. The activities of sucrose metabolism enzymes among wild A. eriantha varieties (lines) were different to some extent. The sucrose metabolism-related enzyme genes among wild A. eriantha germplasm resources had different expression patterns. The results will contribute to understanding the fruit quality changes and the mechanism of sugar metabolism in wild A. eriantha at the soft ripening stage, and lay a foundation for the protection and utilization of wild A. eriantha germplasm resources

    Insight into the Double-Edged Role of Ferroptosis in Disease

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    Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis

    The Removal Mechanism Considering the Shape and Size of Abrasive Particles in Wet Blast Cleaning of Paint

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    Recently, wet blast cleaning of paint has attracted attention in remanufacturing processes, owing to its high efficiency and environmental friendliness. However, studies of removal mechanism have rarely considered the properties of abrasive particles; thus, there is insufficient theoretical guidance on the process optimization, resulting in energy waste during the cleaning process. Therefore, the mechanism in wet blast cleaning of paint was researched in this study, which focused on the effects of abrasive particle shape and size on mechanism. The results indicate that the removal mechanisms of angular and spherical abrasive particles are significantly different, and that of angular abrasive particles is not affected by the particle size, whereas that of spherical abrasive particles is significantly affected. The main removal mechanism for all angular abrasive particles is brittle fracture caused by large impact stresses. For large spherical abrasive particles (&ge;60-mesh), the main mechanism is brittle fracture due to the intersection of longitudinal-through fatigue cracks and interface cracks, and for small spherical abrasive particles (&le;80-mesh), it is brittle fracture due to fatigue cracks and impact cracks. This study provides good insight into abrasive particles and serves as a good basis for exploring the process parameters for wet blast cleaning

    Research on Biological Detection Based on Reflected Light Images of a Porous Silicon Bragg Mirror

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    In this paper, based on the gray value change of reflected light image of porous silicon (PSi) Bragg mirror, a fast and simple biological detection method is proposed. In this method, CdSe/ZnS quantum dots (QDs) are used as markers for refractive index amplification, and digital image method is used for detection. The detection light has the same wavelength as the lowest reflectivity of the edge of the Bragg mirror, and the reflected light radiated on the surface of the Bragg mirror is received by the detector. The theoretical simulation results show that the intensity of the reflected light increases with the increase of the refractive index caused by the biological reaction. According to the experimental results, the average gray value variation increases with the increase of the target DNA concentration and becomes a linear relationship in a certain range. Based on this method, the DNA detection limit is 20.74 pM. The method is low-cost, has a short detection time and can be used in the detection of biosensor microarray
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