Background: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor globally, with high incidence and mortality rates that seriously endanger human health. While traditional therapeutic approaches have demonstrated some efficacy in controlling disease progression, they are still fraught with numerous limitations. In recent years, plant-derived nanovesicles have garnered significant attention owing to their distinctive biological activities and promising antitumor characteristics. The effects of Fagopyrum dibotrys, a plant with various medicinal values, and its-derived nanovesicles (FdNVs) on HCC cells have not been clarified.Objective: This study aimed to explore the inhibitory effects of FdNVs on human HCC cells and subcutaneous xenograft tumors, as well as the underlying molecular mechanisms.Methods: FdNVs were isolated and purified through ultracentrifugation, characterized via Nanoparticle Tracking Analysis (NTA) and Transmission Electron Microscopy (TEM), and subsequently evaluated in vitro using the HepG2 HCC cell line to assess their effects on proliferation (via cell viability, EdU, and colony formation assays), migration (wound healing assay), and invasion (Transwell assay), while mitochondrial ultrastructural changes were examined by TEM, intracellular ROS and Fe²⁺ levels were measured fluorometrically, oxidative stress markers (GSH and MDA) were quantified colorimetrically, ferroptosis-related mRNA and protein expression were analyzed by RT-qPCR and Western blot, followed by in vivo validation of their antitumor efficacy in a nude mouse HepG2 xenograft model.Results: In vitro studies demonstrated that FdNVs dose-dependently suppressed HepG2 cell proliferation, motility, and invasive capacity. Mechanistic investigations revealed that this inhibitory effect was mediated through ferroptosis activation, supported by the following observations: elevated intracellular ferrous iron (Fe²⁺) and reactive oxygen species (ROS), reduced glutathione (GSH) content, disrupted mitochondrial ultrastructure, and modulated expression of key ferroptosis regulators—including upregulation of pro-ferroptotic proteins (p53 and ALOX15) and downregulation of anti-ferroptotic factors (xCT and GPX4). Furthermore, in vivo studies validated the tumor-suppressive role of FdNVs, confirming their capacity to trigger ferroptosis in HepG2 xenografts.Conclusion: FdNVs inhibited the proliferation, migration and invasion of HCC cells by inducing iron death, and their anti-tumor mechanism involved the regulation of iron death-related genes and proteins.

Objective Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD. Methods Firstly, the network pharmacology was used to screen the RosA targets, and LUAD-related differential expressed genes (DEGs) were acquired from the GEO database. The intersection of LUAD regulated by RosA (RDEGs) was obtained through the Venn diagram. Secondly, GO and KEGG enrichment analysis of RDEGs were performed, and protein–protein interaction networks (PPIs) were constructed to identify and visualize hub RDEGs. Then, molecular docking between hub RDEGs and RosA was performed, and further evaluation was carried out by using bioinformatics for the predictive value of the hub RDEGs. Finally, the mechanism of RosA in the treatment of LUAD was verified by establishing a xenograft model of NSCLC in nude mouse. Results Bioinformatics and other analysis showed that, compared with the control group, the expressions of MMP-1, MMP-9, IGFBP3 and PLAU in LUAD tissues were significantly up-regulated, and the expressions of PPARG and FABP4 were significantly down-regulated, and these hub RDEGs had potential predictive value for LUAD. In vivo experimental results showed that RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells. Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells. In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells. Conclusions This study demonstrated that RosA could induce apoptosis by regulating the PPAR signaling pathway and the expression of MMP-9, inhibit the proliferation, migration and invasion of lung cancer cells, thereby exerting anti-LUAD effects. This study provides new insight into the potential mechanism of RosA in treating LUAD and provides a new therapeutic avenue for treatment of LUAD.

Introduction: Prognostic heterogeneity is common in patients with hepatocellular carcinoma (HCC) within the same clinical stage. While the albumin–bilirubin (ALBI) score and systemic immune-inflammation index (SII) have individual prognostic value, their combined significance remains unclear. We aimed to develop a novel ALBI-SII grade and a prognostic nomogram to refine risk stratification. Methods: This retrospective study included 210 patients with HCC diagnosed between 2013 and 2021. A novel ALBI–SII grade was constructed by integrating ALBI and SII. Overall survival (OS) was analyzed using Kaplan–Meier methods and Cox regression based on a multiple imputation dataset. A nomogram incorporating ALBI–SII grade and China Liver Cancer (CNLC) staging was developed and validated using time-dependent ROC curves, DeLong’s test, and decision curve analysis (DCA). Results: The ALBI–SII grade stratified patients into three distinct risk groups (Median OS: Grade 0, 639 days; Grade 1, 310 days; Grade 2, 148 days; P < 0.001). In multivariate analysis, ALBI-SII grade remained an independent prognostic factor (Grade 2 vs. 0: HR = 2.576, 95% CI: 1.654–4.012, P < 0.001). The 5-year AUC of ALBI-SII was 0.735, which was statistically comparable to that of CNLC staging (AUC = 0.724; DeLong’s P > 0.05). The nomogram demonstrated robust discrimination (C-index: 0.695) and favorable clinical net benefit. Conclusion: The ALBI–SII grade is an objective and practical prognostic indicator for HCC. A nomogram integrating ALBI–SII and CNLC staging provides reliable survival prediction, particularly for long-term outcomes.

Understanding the role of the tumor microenvironment in colorectal cancer (CRC) progression remains a challenge due to its complexity. Investigating the interplay between immune cell characteristics, serum metabolites, inflammatory protein factors, and CRC could unveil novel therapeutic avenues. We used 2-sample Mendelian randomization (MR) on Genome-Wide Association Studies (GWAS) data to explore causal links between 731 immune cell characteristics, 1400 serum metabolites, 91 inflammatory proteins, and CRC. Various MR methods, including inverse variance weighted (IVW) and MR-Egger, were applied to ensure robust analysis. Sensitivity analyses, such as the MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis, were performed to check for pleiotropy, heterogeneity, and influential outliers. Following rigorous genetic variation screening, we identified 43 immune cell characteristics associated with CRC. Notably, 7 immunophenotypes, including CD39⁺ CD4⁺ T cell Absolute Count, exhibited significant associations as protective factors. Additionally, 36 other immunophenotypes showed significant causal relationships with CRC. Among serum metabolites, 37 were correlated with CRC, with 1-arachidonoyl-gpc (20: 4n6) being the most closely linked as a risk factor. Similarly, 36 serum metabolites displayed significant causal relationships with CRC. Seven inflammatory protein factors exhibited causal relationships with CRC, with 4 posing as risk factors and 3 as protective factors. Our study scrutinized 731 immune cell characteristics, 1400 serum metabolites, and 91 inflammatory protein factors within the tumor microenvironment. We confirmed causal relationships between 43 immune cell characteristics, 37 serum metabolites, and 7 inflammatory protein factors with CRC. These findings offer novel insights into the potential etiology, prevention, and treatment strategies for CRC.