Background Hepatocellular carcinoma (HCC) is a prevalent malignancy with a pressing need for improved therapeutic response and prognosis prediction. This study delves into a novel predictive model related to ferroptosis, a regulated cell death mechanism disrupting metabolic processes.Results Single-cell sequencing data analysis identified subpopulations of HCC cells exhibiting activated ferroptosis and distinct gene expression patterns compared to normal tissues. Utilizing the LASSO-Cox algorithm, we constructed a model with 10 single-cell biomarkers associated with ferroptosis, namely STMN1, S100A10, FABP5, CAPG, RGCC, ENO1, ANXA5, UTRN, CXCR3, and ITM2A. Comprehensive analyses using these biomarkers revealed variations in immune infiltration, tumor mutation burden, drug sensitivity, and biological functional profiles between risk groups. Specific associations were established between particular immune cell subtypes and certain gene expression patterns. Treatment response analyses indicated potential benefits from anti-tumor immune therapy for the low-risk group and chemotherapy advantages for the high-risk group.Conclusions The integration of this single-cell level model with clinicopathological features enabled accurate overall survival prediction and effective risk stratification in HCC patients. Our findings illuminate the potential of ferroptosis-related genes in tailoring therapy and prognosis prediction for HCC, offering novel insights into the intricate interplay among ferroptosis, immune response, and HCC progression.

重楼具有清热解毒、消肿止痛、化瘀止血、息风定惊等功效.国医大师徐景藩教授治疗内科疑难疾病时,常用重楼进行配伍,尤擅用其治疗溃疡性结肠炎,并总结重楼具有抑炎止痢、利咽止痛、调节免疫、抗萎防癌等功效,进而拓展重楼临证应用范围.现整理徐景藩教授运用重楼配伍诊治溃疡性结肠炎、扁桃体肿大、类风湿关节炎、慢性萎缩性胃炎四则医案,与飨同道.

Background Baicalin is an important active flavonoid isolated from the roots of Scutellaria baicalensis (S. baicalensis), a well-known traditional Chinese herb used in treating inflammatory bowel disease (IBD). The objectives of this study were to assess the potential benefit of baicalin in experimental colitis, as well as to investigate metabolic biomarkers of experimental colitis in conjunction with network pharmacology. Methods Using a widely utilized network pharmacology technique, baicalin’s targets and pathways were predicted. Simultaneously, experimental colitis was induced by intrarectal administration of TNBS. Histopathology examinations were performed to confirm pathological changes. Plasma samples were examined by using an untargeted metabolomics technique based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen differential metabolites and associated metabolic pathways. Additionally, network pharmacology and integrated analysis of metabolomics were used to identify the primary targets. Results Through network pharmacology research, tumor necrosis factor (TNF), interleukin 6 (IL6), serine/threonine-protein kinase (AKT1), and other 7 proteins were found to be the main targets of baicalin against IBD. The untargeted metabolomics results showed that 47 metabolites in glycerophospholipids and sphingolipid metabolism were involved as key pathways in the experimental colitis model group. 19 metabolites, including Sphingomyelin (SM d42:2, SM d42:1, SM d34:1), Lysophosphatidic acids (LPA 18:4), 1-Palmitoylglycerophosphocholine, and 17(18)-EpETE were demonstrated as key metabolites for baicalin to exert effects. Moreover, udp-glucose ceramide glucosyltransferase (UGCG), sphingomyelin synthase 1 (SGMS1), and sphingosine kinase (SPHK1) were predicted as sphingolipids-linked targets of baicalin against experimental colitis by integrative analysis. Conclusion Based on these results, it implies that sphingolipid metabolism and sphingolipid signaling pathway might be acted as therapeutic mechanism for baicalin against experimental colitis.

目的:通过重楼总皂苷(RPTS)对三硝基苯磺酸(TNBS)诱导的急性实验性结肠炎小鼠治疗作用及机制研究,以期为人类炎症性肠病治疗提供新策略.方法:将40只雄性SPF级BALB/c小鼠,随机分为正常对照(normal control,NC)组、TNBS模型(TNBS model,TM)组、美沙拉嗪(mesalazine,ME)组及重楼总皂苷(rhizoma paridis total saponins,RS)组,每组 10只.比较各组小鼠的一般情况、肠组织mRNA与蛋白表达情况以及血清细胞因子等指标.结果:通过RPTS的干预,与TM组比较,RS组TLR2、TLR4 及NF-κB的mRNA均降低(P<0.05);且IL-1β及TNF-α的mRNA表达呈现下降趋势.在IHC蛋白表达检测中,RS组相较于TM组TLR2及TLR4的蛋白水平均下降(P<0.05);在NF-κB的蛋白表达中,RS组相较TM组也呈现降低.在血清细胞因子中,与TM组比较,RS组TNF-α、CCL20/MIP-3α、CCL4/MIP-1β及IL-17 等多数细胞因子升高;CCL3/MIP-1α呈下降趋势.结论:RPTS对急性实验性结肠炎小鼠有治疗作用,提高了小鼠终点生存率,其机制可能与RPTS下调结肠黏膜局部TLR2&4/NF-κB炎性信号通路有关.同时,通过调节血清中细胞因子水平,发挥适度免疫调控机制进而对机体起到保护作用,以缓解模型鼠的全身炎症及免疫反应,其潜在机制有待进一步研究.

Aims. This study aims to investigate the potential biomarkers of inflammatory bowel disease (IBD) and IBD with damp-heat syndrome (IBD-DH) by metabolomics. Methods. Plasma and urine samples were collected from 15 healthy controls and 30 IBD patients, including 15 IBD-DH and 15 IBD with spleen deficiency syndrome (IBD-SD), which was coded as SF8G and SF70 according to the International Classification of Diseases Eleventh Revision (ICD-11) issued by World Health Organization. Pseudotargeted metabolomics method was used based on ultra-high-performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry. Results. Under the condition of false discovery rate (FDR) < 0.05, variable importance projection (VIP) > 1.0, and fold change (FC) > 1.5 or < 2/3, we found 57 plasma differential metabolites and 20 urinary differential metabolites in IBD. Then, with area under the curve (AUC) ≥ 0.85 and FC ≥ 2 or ≤ 0.3, 11 potential biomarkers were identified, such as acylcarnitine (ACar 20:4, ACar 18:1, and ACar 20:3), 3-indoleacetic acid, hippuric acid, and dehydroepiandrosterone sulfate, which is related to intestinal microbiota and immune response. However, less obvious differences were observed in IBD-DH when compared with IBD-SD. Under the condition of FDR < 0.2, VIP >1.0, and FC > 1.5 or < 2/3, we identified 16 plasma differential metabolites. In urine samples, IBD-DH and IBD-SD had the same metabolite pattern. With AUC ≥ 0.80, 7 differential plasma metabolites, mainly glycerophospholipids, were identified in IBD-DH. Kyoto Encyclopedia of Genes and Genomes analysis indicated that metabolic pathways, such as citrate cycle and amino acids metabolism, were mainly responsible for the distinction between IBD and healthy controls, whereas glycerophospholipid metabolism perturbation was not only a manifestation of IBD but also an important pathway to distinguish two subtypes defined by traditional medicine, IBD-DH and IBD-SD. Conclusion. In this study, we found that several metabolites of aromatic acids and lipid derivatives could act as potential biomarkers to discriminate IBD from healthy controls. Glycerophospholipids metabolites might be used to differentiate IBD-DH from IBD-SD.