The chromodomain helicase DNA binding domain 5 (CHD5) is required for neural development and plays an important role in the regulation of gene expression. Although CHD5 exerts a broad tumor suppressor effect in many tumor types, its specific functions regarding its expression levels, and impact on immune cell infiltration, proliferation and migration in glioma remain unclear. Here, we evaluated the role of CHD5 in tumor immunity in a pan-cancer multi-database using the R language. The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets were utilized to determine the role of CHD5 in 33 types of cancers, including the expression level, prognosis, tumor progression, and immune microenvironment. Furthermore, we explored the effect of CHD5 on glioma proliferation and migration using the cell counting kit 8 (CCK-8) assay, transwell assays and western blot analysis. The findings from our pan-cancer analysis showed that CHD5 was differentially expressed in the tumor tissues as compared to the normal tissues. Survival analysis showed that CHD5 was generally associated with the prognosis of glioblastoma (GBM), low Grade Glioma (LGG) and neuroblastoma, where the low expression of CHD5 was associated with a worse prognosis in glioma patients. Then, we confirmed that the expression level of CHD5 was associated with tumor immune infiltration and tumor microenvironment, especially in glioma. Moreover, si-RNA mediated knockdown of CHD5 promoted the proliferation and migration of glioma cells in vitro. In conclusion, CHD5 was found to be differentially expressed in the pan-cancer analysis and might play an important role in antitumor immunity. CHD5 is expected to be a potential tumor prognostic marker, especially in glioma.

Background: A stable and standardized source of mesenchymal stem cells is a prerequisite for bone repair tissue engineering research and application. We aimed to establish a stable cell line of bone marrow mesenchymal stem cells from New Zealand rabbits and explore their osteogenic differentiation capacity.Methods: Primary rabbit bone marrow mesenchymal stem cells (RBMSCs) were isolated and immortalized via retroviral expression of SV40 Large T antigen (LTA). To assess the osteogenic differentiation capacity of the cells in vitro, we studied the alkaline phosphatase (ALP) expression level and calcium deposition in bone morphogenetic protein 9 (BMP9)‐induced immortalized cells using ALP staining and quantification, as well as alizarin red staining. Ectopic bone formation by the cells was assessed using micro‐computed tomography (μCT) and histological examination.Results: The immortalized cell line we established using SV40 LTA, which we termed iRBMSCs, was non‐tumorigenic and maintained long‐term proliferative activity. We further discovered that BMP9 (MOI = 30) effectively induced the osteogenic differentiation capacity of iRBMSCs in vitro, and there was a synergy with GelMA hydrogel in inducing osteogenic differentiation of the iRBMSCs in vivo.Conclusion: We confirmed that iRBMSCs are promising as a stable cell line source for bone defect repair engineering.

Background/Objectives: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat. Methods: Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst. Results: ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment. Conclusions: Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments.

Glucocorticoid (GCs), as an adjuvant drug, is widely used for alleviating chemotherapy or immunotherapy-induced adverse events, such as nausea and immune-related diseases in lung cancer treatment. However, whether GCs directly affects lung cancer progression remains unclear. This study focused on the effects of dexamethasone (DEX) on the proliferation and migration of lung cancer cells as well as the related potential mechanisms using EdU, CCK8, Transwell, Wound healing, TCGA database, HPA database, qPCR and Western blotting. Additionally, subcutaneous tumor and tail vein tumor injection models were established for investigating DEX action in vivo. Further, to confirm the key functional of Smad2/3 for DEX regulating lung cancer cells proliferation and migration. Mechanistic assays explored the upstream regulatory molecules TGFβ1, TGFβR1 and p-TGFβR1 expression after DEX treatment. Moreover, DEX modulates lung cancer cell proliferation and migration on a glucocorticoid receptor (GR)-independent manner and the association with Smad2/3 activation were investigated. Results: The results showed that DEX (1 µM) treatment significantly inhibited the proliferation and the migration of lung cancer cells A549 and LLC cells. TCGA and HPA databases showed Smad2/3 expression was positively correlated with lung cancer progression. Mechanistically, DEX treatment significantly inhibited Smad2/3 activation in vitro and in vivo, manifested as a decrease in the expression of p-Smad2 (Ser465/467), Smad2, p-Smad3 (Ser423/425), and Smad3. Smad2/3 knockdown significantly inhibit the proliferation, migration and Smad2/3 activity of A549 and LLC cells. Creatine, the agonist of Smad2/3 activation, markedly reversed the inhibitory effects of DEX on the proliferation and migration of A549 and LLC cells. Smad2/3 overexpression also reversed the inhibitory effects of DEX on A549 cell proliferation and migration. Further studies showed DEX inhibited the expression of TGFβR1 and p-TGFβR1(Ser165) and the levels of TGFβ1. Moreover, GR knockout significantly promoted the proliferation, migration and Smad2/3 activity in A549 cell. DEX can inhibits A549 cell proliferation and migration through suppressing Smad2/3 activation independent of GR. Conclusion: DEX inhibited the proliferation and migration of lung cancer cells by suppressing Smad2/3 activation, providing a theoretical basis and experimental data for clinical practice.