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The copper ion content in the body maintains homeostasis, and when dysregulated, it can produce cytotoxicity and induce cell death through a variety of pathways. Cuproptosis refers to copper ions combining directly with acylated molecules, leading to the accumulation of oligomerization of lipoylated protein and subsequent downregulation of iron-sulfur cluster proteins; this induces proteotoxic stress and cell death. This study on the relationship between cuproptosis-related lncRNAs (CRLns) and the prognosis of primary hepatic carcinoma (PHC) has important clinical guiding significance for the diagnosis and treatment of PHC. Prognosis-related CRLRs were identified via rank-sum tests, correlational analyses, and univariate Cox regression, and a CRLR risk-scoring model (CRLRSM) was constructed using LASSO Cox regression. Patients were divided into high-risk and low-risk groups based on the median CRLRSM scores. Variance analysis for cuproptosis-related genes, gene set enrichment analysis, and correlational analysis for risk and immunity were performed using boxplots. Quantitative polymerase chain reactions were used to verify the CRLR levels in PHC cell lines. The study results showed that patients in the CRLRSM high-risk group had worse survival rates than those in the low-risk group. The PHC stage and risk score were independent prognostic factors for hepatocellular carcinoma. There were 7 CRLRs (MIR210HG, AC099850.3, AL031985.3, AC012073.1, MKLN1-AS, KDM4A-AS1, and PLBD1-AS1) associated with PHC prognosis, primarily through cellular metabolism, growth, proliferation, apoptosis, and immunity. In conclusion, the overexpression of 7 CRLRs in patients with PHC indicates a poor prognosis.
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OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. This study was designed to uncover the healing effect of friedelin, a bioactive compound against UC through bioinformatics of network pharmacology and experimental verification of UC model mice. MATERIALS AND METHODS: Targets of friedelin and potential mechanism of friedelin on UC were predicted through target searching, PPI network establishing, and enrichment analyzing. We explored effects of friedelin on dextran sulfate sodium (DSS)-induced colitis. Severity of UC was investigated by body weight, disease activity index (DAI), and length of the colon. Inflammation severity was examined by determination of proinflammatory and anti-inflammatory cytokines. The numbers of autophagosome around the epithelial cells were observed by autophagy inhibition via a transmission electron microscope. The expressions of autophagy-related ATG5 protein and AMPK-mTOR signaling pathway were determined by immunofluorescence staining. RESULTS: In this study, 17 potential targets of friedelin and 1111 UC-related targets were identified. 10 therapeutic targets of friedelin against UC were acquired from overlapped targets of UC and friedelin. PPI network construction filtered 14 core targets through target amplification and confidence enhancement. The results of molecular docking showed that the docking scores of the top 5 active targets were higher than the threshold values. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out, showing friedelin alleviates UC through anti-inflammatory pathways and molecular function of autophagy. Subsequently, animal-based experiments revealed the intraperitoneal injection of friedelin ameliorated DSS-induced body weight loss, DAI decrease, colon length shortening and colonic pathological damage with lower myeloperoxidase and proinflammatory cytokines (IL-1ß and IL-6) and higher IL-10 levels, and more autophagosomes in transmission electron microscope results. The AMPK-mTOR signaling pathway plays important role in the friedelin's effect in autophagy as KEGG pathway result and experiment verification. Furthermore, the 3 ma validated the role of autophagy as an improvement in the friedelin's pharmacologic effect to UC model mice. CONCLUSIONS: Friedelin ameliorated DSS-induced colitis in mice through of inflammatory inhibition and regulation of autophagy.
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OBJECTIVE: To study the Chinese medicine (CM) syndrome features of ulcerative colitis (UC) by using fluorescence intensity (the ratio of green to red, G/R ratio) of auto fluorescence imaging, thus providing objective evidences for the CM syndrome typing of UC. METHODS: Totally 49 patients were recruited. They were typed as Dachang damp-heat syndrome (19 cases), Pi-Wei qi deficiency syndrome (30 cases), and the healthy control group (21 cases) on the bases of mucosal morphology of white light endoscopy (WLE) and the G/R ratio of AFI. RESULTS: Compared with the healthy control group (1.227 +/- 0.137), the G/R ratio in Dachang damp-heat syndrome (0.915 +/- 0.114) and Pi-Wei qi deficiency syndrome (1.147 +/- 0.137) decreased with statistical difference (P < 0.05, P < 0.01). Of them, it was lower in Dachang damp-heat syndrome group (P < 0.01). The case number was mainly dominated in moderate endoscopic index (EI) (11 cases) and severe EI (5 cases) in Dachang damp-heat syndrome group. The case number was mainly dominated in the remission phase (17 cases) and mild EI (7 cases) in Pi-Wei qi deficiency syndrome group. The G/R ratio of the remission phase was higher than that of the active phase (1.220 vs. 0.963, P < 0.01). There was statistical difference in the G/R ratio of the mild EI (1.044), the moderate EI (0.967), and the severe EI (0.830) (P < 0.01). CONCLUSIONS: The inflammation degree of Dachang damp-heat syndrome was more severe than that of Pi-Wei qi deficiency syndrome. AFI could better reflect the inflammation degree of UC.