Objective To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP‐4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration. Methods Using RNase protection assays and enzyme‐linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP‐1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression. Results The interleukin‐6 (IL‐6)–type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL‐6 nor tumor necrosis factor α could stimulate the expression of CCL13 in synovial fibroblasts; IL‐1β was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT‐5, ERK‐1/2, and p38 as critical factors involved in OSM‐dependent transcription and messenger RNA stabilization of CCL13. Conclusion In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up‐regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM‐induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue‐specific imprinting of different fibroblasts during development.
Background: Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can obtain semiquantitative or quantitative parameters of tumors by capturing the images before and after injection of contrast medium. However, there has been no further research on the effect of flow rate of contrast medium on image quality and parameter sensitivity of DCE-MRI in endometrial carcinoma (EC).Methods: This was a prospective cohort study enrolling patients who were suspected of EC between January 2018 and June 2020. The baseline data of participants were collected. Post-surgical histological examination acted as the gold standard of EC diagnosis and some characteristics of tumors were recorded.We calculated 3 important parameters of DCE-MRI, including volume transfer constant (K trans ), flux rate constant (K ep ), and extravascular extracellular volume fraction (V e ), according to the MRI system. The image quality in DCE-MRI imaging was evaluated according to contrast, resolution, artifact, signal-to-noise ratio, and scanning time. To evaluate the diagnostic ability of DCE-MRI with different injection rate, receiver operating characteristic (ROC) curve was generated and the area under curve (AUC) was calculated.Results: According to the different injection rate of contrast medium, participants were divided into three groups, including 2, 3, and 4 mL/s group. It was found that there were more grade 1 EC in the 3 mL/s group (52.4%) than other two groups (34.3% and 23.3%, respectively), and the difference was significant (P=0.021).No other significant differences were found among all other variables. It was found that K trans was much higher in the 4 mL/s group than in other two groups (P<0.001). Also, V e was much higher in the 4 mL/s group than in other two groups (P<0.001). However, no significant difference was found in K ep between three groups (P=0.633). Besides, the 4 mL/s group had the highest quality of all three groups (P<0.001). The sensitivity, specificity, and accuracy were highest in 4 mL/s group. The AUC in three groups were 0.822, 0.832, and 0.888 in the 2, 3, and 4 mL/s group, respectively. Conclusions:The DCE-MRI measurement is useful for the diagnosis of EC, and faster injection rate may be beneficial to improve diagnostic accuracy and image quality.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.