NPRL2 may act as a pro-growth factor in PCa. The high levels of NPRL2 expression in CRPC promote resistance to EVS by enhancing autophagy. NPRL2 may be a new therapeutic target for intervention of CRPC and a biomarker for predicting resistance to EVS in CRPC.

Background Modified Sijunzi decoction (SJZD) has been used to treat ulcerative colitis (UC) in remission. However, more rigorous clinical trials are necessary to evaluate its effectiveness. Therefore, a series of single-case randomised controlled trials (N-of-1 trials) is proposed to compare the efficacy of modified SJZD with mesalazine for treating UC in remission. Methods This is a single-site, hospital-based, double-blind N-of-1 trial for 10 single subjects. Three cycles of N-of-1 trials are planned. There are two treatment periods in each cycle. Modified SJZD combined with mesalazine placebo or mesalazine combined with modified SJZD placebo will be randomised during each 8-week treatment period. There is no washout period in the study. Subjects will be selected by the researcher strictly in accordance with the inclusion and exclusion criteria. Discussion Paired t tests and mixed-effect models will be used to analyse the visual analogue scale (VAS) for clinical symptoms and the quality of life questionnaire responses. The findings will be interpreted with caution. We anticipate that the results will show that modified SJZD is effective for patients with UC in remission. Trial registration Chinese Clinical Trial Register, ID: ChiCTR1900024086. Registered on 24 June 2019.

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA.Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments.Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone.Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.

Background. This current study applied bioinformatics analysis to reveal the crosstalk between venous thromboembolism (VTE) and periodontitis, as well as the potential role of immune-related genes in this context. Methods. Expression data were downloaded from the GEO database. Blood samples from venous thromboembolism (VTE) were used (GSE19151), while for periodontal disease, we used gingival tissue samples (GSE10334, GSE16134, and GSE23586). After batch correction, we used “limma” packages of R language for differential expression analysis ( p value < 0.05, ∣ logFC ∣ ≥ 0.5 ). We used Venn diagrams to extract the differentially expressed genes common to VTE and periodontitis as potential crosstalk genes and applied functional enrichment analysis (GO biological process and KEGG pathway). The protein-protein interaction (PPI) network of crosstalk genes was constructed by Cytoscape software. The immune-related genes were downloaded from the literature. The Wilcoxon test was used to test the scores of immune infiltrating cells. The crosstalk genes were further screened by LASSO Logistic Regression. Results. For periodontitis, 427 case and 136 control samples, and for VTE, 70 case and 63 control samples were included. The obtained PPI network had 1879 nodes and 2257 edges. Moreover, 782 immune genes and 28 cell types were included in the analysis. Over 90% of immune cells had different expressions in VTE and periodontitis. We obtained 12 significant pathways corresponding to crosstalk genes. CD3D, CSF3R, and CXCR4 acted as an immune gene and a crosstalk gene. We obtained a total of 12 shared biomarker crosstalk genes. Among those 12 biomarker crosstalk genes, 4 were immune genes (LGALS1, LSP1, SAMSN1, and WIPF1). Conclusion. Four biomarker crosstalk genes between periodontitis and VTE were also immune genes, i.e., LGALS1, LSP1, SAMSN1, and WIPF1. The findings of the current study need further validation and are a basis for development of biomarkers.

No abstract