Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.

Sepsis is a complex syndrome resulting from an aberrant host response to infection. A hallmark of sepsis is the failure of the immune system to restore balance, characterized by hyperinflammation or immunosuppression. However, the net effect of immune system imbalance and the clinical manifestations are highly heterogeneous among patients. In recent years, research interest has shifted from focusing on the pathogenicity of microorganisms to the molecular mechanisms of host responses which is also associated with biomarkers that can help early diagnose sepsis and guide treatment decisions. Despite significant advancements in medical science, sepsis remains a major challenge in healthcare, contributing to substantial morbidity and mortality worldwide. Further research is needed to improve our understanding of this condition and develop novel therapies to improve outcomes for patients with sepsis. This review explores the related signal pathways of sepsis and underscores recent advancements in understanding its mechanisms. Exploration of diverse biomarkers and the emerging concept of sepsis endotypes offer promising avenues for precision therapy in the future.

The role of macrophages has transcended the traditional binary framework of M1/M2 polarization, emerging as “tissue microenvironment engineers” that dynamically govern organismal homeostasis and disease progression. Under physiological conditions, they maintain balance through phagocytic clearance, metabolic regulation (e.g., lipid and iron metabolism), and tissue-specific functions (such as hepatic detoxification by Kupffer cells and intestinal microbiota sensing), all meticulously orchestrated by epigenetic mechanisms and neuro-immune crosstalk. In pathological states, their functional aberrations precipitate chronic inflammation, fibrosis, metabolic disorders, and neurodegenerative diseases. Notably, this plasticity is most pronounced within the tumor microenvironment (TME): tumor-associated macrophages (TAMs) polarize toward a protumoral phenotype under conditions of low pH and high reactive oxygen species (ROS). They promote angiogenesis via vascular endothelial growth factor (VEGF), suppress immunity through interleukin-10 (IL-10)/programmed death-ligand 1 (PD-L1), and facilitate tumor invasion by degrading the extracellular matrix, ultimately fostering an immune-evasive niche. Novel intervention strategies targeting TAMs in the TME have shown remarkable efficacy: CRISPR-Cas9 spatiotemporal editing corrects aberrant gene expression; pH/ROS-responsive nanoparticles reprogram TAMs to an antitumoral phenotype; chimeric antigen receptor-macrophage (CAR-M) 2.0 enhances antitumor immunity through programmed death-1 (PD-1) blockade and IL-12 secretion; and microbial metabolites like butyrate induce polarization toward an antitumor phenotype. Despite persisting challenges—including the functional compensation mechanisms between tissue-resident and monocyte-derived macrophages, and obstacles to clinical translation—the macrophage-centered strategy of “microenvironmental regulation via cellular engineering” still holds revolutionary promise for the treatment of tumors and other diseases.

The tumor microenvironment (TME) is a complex and dynamic system composed of immune cells, stromal cells, and extracellular matrix (ECM), whose composition and spatial architecture critically influence tumor initiation, progression, invasion, metastasis, and response to immunotherapy. However, traditional research models such as two-dimensional cell coculture, patient-derived xenograft models, and conventional patient-derived organoid (PDO) systems remain limited in simulating the complexity and physiological relevance of the TME. Three-dimensional (3D) bioprinting technology, with its precise spatial control capabilities and advantages in multicellular integration, has emerged as a promising engineering tool for constructing TME-like models with controlled spatial architecture, tunable matrix properties, and programmable multicellular organization. This review examines the principles and capabilities of major 3D bioprinting technologies (extrusion-based, droplet-based, photopolymerization-based) and evaluates their applications in reconstructing key TME features such as matrix remodeling, vascularization, immune cell integration, and drug response modeling with organoids. Importantly, we distinguish between bioprinted organoid-based systems and bioprinted tumor cell models, highlighting their differences in biological fidelity and translational relevance. In addition, challenges including limited integration of PDO, constraints in multicellular coculture, and insufficient long-term functional stability continue to restrict the physiological relevance of these models. Overall, this review provides an engineering-oriented perspective on the current state of bioprinted TME models and outlines practical directions for developing more physiologically relevant platforms for cancer research, drug screening, and precision oncology.