Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of immune cells in the synovium. However, the crosstalk of immune cells and synovial fibroblasts is still largely unknown. Here, global miRNA screening in plasma exosomes was carried out with a custom microarray (RA patients vs. healthy controls = 9:9). A total of 14 exosomal miRNAs were abnormally expressed in the RA patients. Then, downregulated expression of exosomal miR-204-5p was confirmed in both the replication (RA patients vs. healthy controls = 30:30) and validation groups (RA patients vs. healthy controls = 56:60). Similar to the findings obtained in humans, a decreased abundance of exosomal miR-204-5p was observed in mice with collagen-induced arthritis (CIA). Furthermore, Spearman correlation analysis indicated that plasma exosomal miR-204-5p expression was inversely correlated with disease parameters of RA patients, such as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. In vitro, our data showed that human T lymphocytes released exosomes containing large amounts of miR-204-5p, which can be transferred into synovial fibroblasts, inhibiting cell proliferation. Overexpression of miR-204-5p in synovial fibroblasts suppressed synovial fibroblast activation by targeting genes related to cell proliferation and invasion. In vivo assays found that administration of lentiviruses expressing miR-204-5p markedly alleviated the disease progression of the mice with CIA. Collectively, this study identified a novel RA-associated plasma exosomal miRNA-204-5p that mediates the communication between immune cells and synovial fibroblasts and can be used as a potential biomarker for RA diagnosis and treatment.Subject terms: Diagnostic markers, Non-coding RNAs相似文献
Application of the shallow water waves in environmental engineering and hydraulic engineering is seen. In this paper, a (3+1)-dimensional generalized nonlinear evolution equation (gNLEE) for the shallow water waves is investigated. The Nth-order Wronskian, Gramian and Pfaffian solutions are proved, where N is a positive integer. Soliton solutions are constructed from the Nth-order Wronskian, Gramian and Pfaffian solutions. Moreover, we analyze the second-order solitons with the influence of the coefficients in the equation and illustrate them with graphs. Through the Hirota-Riemann method, one-periodic-wave solutions are derived. Relationship between the one-periodic-wave solutions and one-soliton solutions is investigated, which shows that the one-periodic-wave solutions can approach to the one-soliton solutions under certain conditions. We reduce the (3+1)-dimensional gNLEE to a two-dimensional planar dynamic system. Based on the qualitative analysis, we give the phase portraits of the dynamic system.
In this research, the hydrogen bonds Y···H-X(X = C, N; Y = N, O) of thymine and uracil have been theoretically studied. The results show that hydrogen bond leads to bond length elongation and stretches the frequency red-shift of N-H···Y. Meanwhile, the C-H···O bonds shorten and stretch the frequency blue-shift. They all belong to traditional hydrogen bonds. The intermolecular charge transfer caused by the intermolecular hyperconjugation ρ*(N–H) →n(Y) and intramolecular charge redistribution by intramolecular hyperconjugation ρ(C-H)→ρ*(C-N) play important roles in the formation of hydrogen bonds. According to the judgment standards proposed by Bader and Popelier, these hydrogen bonds have typical electron density topological properties. Electrostatic surface potential(ESP) is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as the prediction of likely sites of electrophilic and nucleophilic metabolic attack. 相似文献