Purpose Resveratrol (Res) is a natural polyphenolic compound found in several plants and reported as a promising biological molecule with effective anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified the key cellular signaling pathways involved in the Res regulatory process on SSc. Methods Res-targeted genes interaction network was constructed using the STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in both SSc and Res-targeted genes were then identified. The top five enriched KEGG pathways were visualized by GOplot. KEGG pathways associated with Res-targeted genes were established by Pathway Builder Tool 2.0. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines. Results Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as one of the crucial regulatory pathways. In vitro results suggested that SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and partially reversing mTOR-dependent induction of fibrosis and inflammation. Conclusion These results indicated that Res is a feasible and effective choice for SSc and therapeutic target of mTOR could be a potential alternative for treatment of SSc.

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus , which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund’s Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1βand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

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Amelogenin is a complex enamel matrix protein that consists of various molecular-size proteins and amino acids. A spliced form of amelogenin was identified that included exons 2, 3, 5, 6, and 7. However, the biological function of amelogenin exon 5 on dental pulp remains unknown. We designed a synthetic amelogenin exon 5 encoded peptide (SP), which was based on a protein produced by cells in response to the enamel matrix derivative (EMD). We investigated the effect of the SP on potentiation of osteogenesis and its signal pathway in dental pulp stem cells (DPSCs). DPSCs are an important cell for pulp tissue homeostasis. DPSCs were cultured with SP to examine the effect of cell proliferation and osteogenic differentiation. We also investigated the mitogen-activated protein kinase (MAPK) signaling pathway. SP significantly enhanced cell proliferation and the expression of osteogenic differentiation. Moreover, SP promoted the expression of the MAPK signaling pathway. Therefore, amelogenin exon 5 might contribute to dental pulp capping.