Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025059
The transcriptional heterogeneity and cellular ecosystem diversity of HCC await further exploration. Single-cell and bulk RNA sequencing data from HCC cells are analyzed to generate a LASSO model for HCC prognostication. CCK-8, scratch assay, flow cytometry, and ROS assays are used to validate how TREM1 may affect HCC cell biological behaviors in vitro. qPCR, western blot analysis, immunohistochemistry, and flow cytometry are applied in a xenograft model to test the effects of TREM1 knockdown on carcinogenesis and the tumor microenvironment. A single-cell atlas of the multicellular ecosystem comprising 13 cell types in HCC is constructed. On the basis of ligand-receptor marker genes specifically extracted from the cell populations, a prognostic model is defined and subsequently validated in additional clinical cohorts. For the first time, a heterogeneous immune microenvironment is observed between low- and high-risk patients, primarily involving macrophages, CD4+ T cells, M1 macrophages, and regulatory T (Treg) cells. Sufficient evidence validates the positive effects of TREM1 on HCC cell proliferation, migration, and apoptosis. Additionally, TREM1 positively modulates the levels of the proinflammatory cytokines IL-1β, TNF-α, and MCP-1. TREM1 downregulation alters the proportions of M1 macrophages and Tregs in the tumor tissue from our HCC xenograft model. Eventually, the Nrf2/Keap1 signaling pathway, which is related to oxidative stress, is shown to be a key pathway downstream of TREM1 downregulation. In summary, we construct a novel prognostic model for HCC on the basis of ligand-receptor marker genes and investigate the role of TREM1 in HCC progression and its impact on the TME.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21259
BACKGROUND: Thyroid hormones play a critical role in regulating growth, development, energy metabolism, and maintaining homeostasis in mammals. Exercise interventions can modulate thyroid hormones levels through various mechanisms. However, the regulatory effects of exercise on multiple organs via thyroid hormones have not yet been fully elucidated. OBJECTIVE: To summarize thyroid hormones synthesis, metabolism, and its regulation through exercise, and explore its dynamic regulatory functions in the liver, bone, muscle, heart, and brain. METHODS: A comprehensive search was conducted in databases including China National Knowledge Infrastructure (CNKI), WanFang database, VIP, Web of Science, and PubMed for relevant articles published from database inception until February 2025. The search terms were “thyroid hormones, thyroxine, triiodothyronine, thyroid, hypothyroidism, hyperthyroidism, exercise, training, physical activity, liver, hepatic, muscle, bone, osteoporosis, osteoblasts, osteoclasts, heart, myocardium, cardiomyopathy, cardiac, myocardial infarction, brain, cognition, nervous” in Chinese and English. A total of 81 studies were included in this review. RESULTS AND CONCLUSION: Exercise can regulate thyroid hormones levels, reshape tissue-specific expression of deiodinases, or alter target organ thyroid hormone receptor sensitivity, forming dynamic regulation of multiple organs. Exercise interventions have the potential to reverse multi-organ pathological phenotypes caused by thyroid dysfunction, such as metabolic dysfunction-associated fatty liver disease, bone homeostasis imbalance, muscle function decline, cardiac function decline, and cognitive dysfunction. Although existing evidence reveals the regulatory effects of exercise on thyroid hormones, its molecular mechanisms and regulatory effects on multiple organs still need further analysis. In addition, current related studies are mostly based on rodents and mostly aerobic exercise; the extent to which they apply to human metabolic diseases requires more clinical evidence support.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025059
Hepatocellular carcinoma (HCC) remains a highly aggressive malignancy with a five-year survival rate of 12–15%, and unresectable cases exhibit unsatisfactory responses to approved multikinase inhibitors and immune checkpoint blockade. This study integrated single-cell and bulk RNA sequencing to construct a 13-cell-type atlas of the HCC ecosystem and derived a ligand-receptor-based LASSO prognostic model. The model stratified patients into low- and high-risk groups with divergent immune microenvironments, primarily involving macrophages, CD4+ T cells, M1 macrophages, and regulatory T cells. Experimental validation demonstrated that TREM1 promotes HCC cell proliferation, migration, and suppresses apoptosis, while positively modulating IL-1β, TNF-α, and MCP-1. TREM1 knockdown altered M1 macrophage and Treg proportions in a xenograft model and downregulated the Nrf2/Keap1 oxidative stress pathway. Despite a relatively low AUC compared to specialized models, this general network approach offers a novel signature and identifies TREM1 as a potential therapeutic target, though real-world validation and deeper mechanistic studies are warranted.
Chinese Journal of New Drugs•2025•DOI: cast_zgxyzz_1236731781232251260
Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.