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• miR-214 is highly expressed in mice with viral myocarditis (VMC) induced by CVB3 infection. • miR-214 targets and inhibits p53, promoting the activity of cardiac fibroblasts (CFs). • miR-214 targets and inhibits PTEN, activating the PI3K/Akt signaling pathway to promote the growth of CFs. • miR-214 promotes myocardial fibrosis and cardiac mesenchymal transition in VMC mice by regulating p53 and the PTEN-PI3K-Akt signaling pathway. • This study provides a new theoretical basis for exploring the role of miRNA in myocardial fibrosis and cardiac interstitial transformation. This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation. [ABSTRACT FROM AUTHOR]

• FASL reversed shXBP1s-induced suppression of cell apoptosis in AMIO-treated thyroid epithelial follicular cells. • LINC00842 up-regulated FASL expression via inhibition of miR-214. • LINC00842 functioned as a miR-214 sponge in HT patients and thyroid epithelial follicular cells. • XBP1s enhanced LINC00842 expression in HT patients and thyroid epithelial follicular cells. • Knockdown of XBP1s suppressed AMIO-induced thyroid epithelial follicular cells apoptosis. • The AMIO aggravated the endoplasmic reticulum stress responses in HT patients and thyroid epithelial follicular cells. Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease, that eventually lead to hypothyroidism. XBP1s is an endoplasmic reticulum stress related protein and participates in the pathogenesis of several diseases. Nevertheless, the potential role of XBP1s in amiodarone (AMIO)-treated HT patients remains unknown. In this study, AMIO aggravated the endoplasmic reticulum stress responses in HT patients and thyroid epithelial follicular cells. Moreover, MTT assay and flow cytometry analysis revealed that knockdown of XBP1s suppressed AMIO-induced thyroid epithelial follicular cells apoptosis. Mechanically, the Chromatin Immunoprecipitation (ChIP) and luciferase activity assay proved that XBP1s enhanced LINC00842 expression in HT patients and thyroid epithelial follicular cells via binding to LINC00842 promoter. LINC00842 functioned as a miR-214 sponge in HT patients and thyroid epithelial follicular cells. Besides, LINC00842 up-regulated Fas ligand (FASL) expression via inhibition of miR-214. In rescue experiments, overexpression of FASL reversed shXBP1s-induced suppression of cell apoptosis in AMIO-treated thyroid epithelial follicular cells. These findings concluded that AMIO-drove XBP1s aggravated endoplasmic reticulum stress and apoptosis in HT via modulating LINC00842/miR-214/FASL axis, providing a new sight for the therapeutic strategy of AMIO-induced HT. [ABSTRACT FROM AUTHOR]

• Geniposide promotes the proliferation and differentiation of MC3T3-E1 cells. • Geniposide functions in MC3T3-E1 cells by targeting the miR-214. • Geniposide activates the Wnt/β-catenin pathway. The research plans to make sure how Geniposide (GEN) functions in osteoblast proliferation and differentiation. The MC3T3-E1 and ATDC5 cells were treated with the GEN, XAV-939 and/or transfected with microRNA (miR)-214 mimic or corresponding control. Cell viability was detected with the CCK-8. The CyclinD1, Runx2, Osx, Ocn, Wnt3a and β-catenin were individually quantified via western blot. The cell cycle was tested by cell cycle analysis assay. The ALP activity was tested by ALP assay. qRT-PCR was used to examine the miR-214 expression level. The cell viability and the expressions of the CyclinD1, Runx2, Osx, Ocn Wnt3a and β-catenin, as well as the ALP activity were individually and significantly promoted by the GEN. Besides, miR-214 was down-regulated by the GEN. The XAV-939 or the miR-214 mimic destroyed the promotional effect of GEN on these elements above. In conclusion, GEN induced the proliferation and differentiation of the MC3T3-E1 and ATDC5 cells by targeting the miR-214 through Wnt/β-catenin activation. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-α and IL-6. In vitro , limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC. • Limonin ameliorated DSS-induced UC in mice. • Limonin inhibit inflammatory effect in DSS-stimulated colitis. • Limonin modulated the activation of the STAT3, miR-214 and PTEN pathways in UC mice. • Limonin regulated the STAT3/miR-214 signaling pathway in vitro. [ABSTRACT FROM AUTHOR]