To study the molecular mechanism by which the N6-methyladenosine (m6A)-reading protein YTHDC2 regulates macrophage M1 polarization, the expression level of YTHDC2 protein was detected in a macrophage polarization model. Next, the expressions of polarization markers was detected in YTHDC2 knockdown M1 macrophages. YTHDC2 knockdown M1 macrophages were constructed, and YTHDC2 knockdown and wild type M1 macrophages weres equencedusing Illumina Novaseq JP26000/MGISEQ-T7 sequencing platform to identify the differentially expressed genes of the 2 cell groups. The differentially expressed genes were analyzed by geneontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment methods to explore the YTHDC2 regulatory pathway and screen for YTHDC2 downstream target genes. Cellular experiments were used to reveal the role of YTHDC2 downstream target gene fibulin1 (FBLN1) in M1 macrophages. The results showed that YTHDC2 expression was elevated in M1 macrophages. Expression levels of polarization markers were decreased in YTHDC2 knockdown M1 macrophages. 147 differentially expressed genes were identified between YTHDC2 knockdown and wildtype M1 macrophages. FBLN1 expression is up-regulated in YTHDC2 knockdown M1 macrophages. Potential m6A methylation might occur at multiple sites in FBLN1. Expression levels of polarization markers were increased in M1 macrophages with the knockdown of YTHDC2 and FBLN1. Inconclusion, YTHDC2 maypromote macrophage M1 polarization by regulating the m6A modification of FBLN1.

The aim of the study was to investigate the effect of human umbilical cord blood mesenchymal stem cell (hUC-MSC) on immune thrombocytopenia (ITP) mouse model and its regulation on the retinoic acid-relatedorphan receptor γt (ROR-γt)/forkhead winged helix transcription factor 3 (Foxp3) signaling pathway. Healthy hUC-MSCs were isolated and cultured, the growth patterns were observed and identified, and the stably-proliferating primary cells were selected for passaging. Thirty male BALB/c mice were randomly divided into the normal control group (Con group), the ITP model group and the hUC-MSC group, with 10 mice in each group. After corresponding treatments, the general condition of the mice was observed. Peripheral platelet count (PLT) was measured, and serum levels of IL-6, IL-17, IL-10, and TGF-β1 were detected using ELISA. Wright-Giemsa staining was used to evaluate the pathological changes in mouse bone marrow and to count the megakaryocytes. Western blotting and RT-qPCR were used to detect protein and mRNA levels of ROR-γt and Foxp3 in mice spleen and peripheral blood, respectively. The results showed that compared to those of the Con group, the serum IL-6 and IL-17 levels, ROR-γt mRNA and protein expression in spleen and the ROR-γt mRNA and protein expression in peripheral blood were all significantly higher in the ITP model group (all with P＜0.05), while the PLT, serum IL-10 and TGF-β1 levels, Foxp3 mRNA and protein expression in spleen and Foxp3 mRNA and protein expression in peripheral blood were significantly decreased (all with P＜0.05), along with significantly reduced number of platelet-producingmegakaryocytes (P＜0.05). Compared to the ITP model group, the hUC-MSC group showed significantly lower serum IL-6 and IL-17 levels, splenic ROR-γt mRNA and protein expression and peripheral blood ROR-γt mRNA and proteinl evels (all with P＜0.05), but significantly higher PLT, serum IL-10 and TGF-β1 levels, splenic Foxp3 mRNA and protein expression, peripheral blood Foxp3 mRNA and protein expression (all with P＜0.05), and the elevated number of platelet-producing megakaryocytes (P＜0.05). As a result, hUC-MSC can promote platelet formation and increase the number of platelet-producing megakaryocyte, which may relief the symptoms of ITP mice by regulating the expressions of cytokines and the ROR-γt/Foxp3 axis．

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint deformity and loss of function. Due to the complexity of pathological mechanism and diversity of inflammatory cytokines, current treatments still lacks clinical efficacy and new treatment strategies have been continuously explored internationally. There is evidence suggesting that exosome and the miRNA encapsulated in them are involved in the pathogenesis of RA. Exosomal miRNA show great potential as biomarkers for the diagnosis of RA and asdiagnostic tools for accurate identification and target therapy. As the most promising drug delivery vector, exosomes are expected to become one of the new treatment methods for RA. In recent years, researchers have conducted in-depth studies on the role of exosomal miRNA in the pathogenesis and progression of RA. This review summarizes the research progress on the mechanism of exosomal miRNA involved in RA pathogenesis and explores their potential clinical application prospect．