Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H₂O₂). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H₂O₂ and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

This study investigates the size-dependent mechanisms by which polystyrene (PS) microplastics (MPs) cause intestinal epithelial injury, focusing on the differential effects of nanoscale (100 nm) and microscale (10 μm) particles. Using both cellular and animal models, we found that 100 nm MPs are internalized by intestinal epithelial cells via endocytosis, triggering oxidative stress and ferroptosis, while 10 μm MPs primarily induce epithelial damage through mechanical disruption and metabolic reprogramming. Proteomic analyses revealed that small MPs significantly upregulate ferroptosis-related genes, including Fosl1 and components of the p53 pathway. Functional studies showed that Fosl1 promotes p53 transcription, suppresses Slc7a11, and contributes to ferroptosis. Mechanistically, ferroptosis was characterized by intracellular iron accumulation, glutathione (GSH) depletion, GPX4 inactivation, and excessive lipid peroxidation. Treatment with Ferrostatin-1 or Fosl1 knockdown alleviated ferroptosis and epithelial injury. In contrast, large MPs activated the mechanosensitive YAP pathway, leading to cytoskeletal remodeling and a metabolic shift from oxidative phosphorylation to anaerobic glycolysis. This metabolic reprogramming was associated with increased inflammation. These findings demonstrate that microplastic particle size critically determines toxicity mechanisms—ferroptosis for small particles and YAP-mediated metabolic disruption for large ones—and suggest potential therapeutic targets for mitigating microplastic-induced intestinal damage.

Background: Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear. Method: Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion. Results: Among the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC. Conclusions: Our results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.

Gastric cancer (GC) is one of the most deadly malignancies with high morbidity worldwide. Cancer cells exhibited higher level of glucose catabolism than normal cells to meet the needs for rapid growth. Emerging evidences indicated that hyperglycemia has positive effects on the progression of tumor. As a vital regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) was confirmed to have a higher expression level in tumor tissue and correlated with the prognosis of GC patients. However, the role of PFKFB3 in GC patients with hyperglycemia remains unclear. The data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were utilized to analyze the expression level of PFKFB3 and conducted survival analysis of GC patients. Western blot assay was used to detect gene expression at the protein level. Small interfering RNA (siRNA) transfection assay was conducted to down-regulate the expression of PFKFB3. Cell functional assays were carried out to reflect the ability of cell proliferation and migration. The results indicated that PFKFB3 was significantly upregulated and its overexpression was associated with poor prognosis of GC patients. Besides, hyperglycemia stimulated the higher expression of PFKFB3 along with the enhanced proliferation, migration and epithelial–mesenchymal transition (EMT) in GC cells. Knocking down of PFKFB3 effectively reversed the effects of high glucose concentration on GC malignant phenotype and the opposite results were gained when miR-26-5p was inhibited. Therefore, PFKFB3 down-regulated by miR-26-5p inhibited the malignant phenotype of GC with hyperglycemia.

Background: Colon adenocarcinoma (COAD) is a gastrointestinal tumor with a high degree of malignancy. Its deterioration process is closely related to the tumor microenvironment, and transcription factors (TF) play a regulatory role in this process. Currently, there is a lack of exploration between the genes related to the COAD tumor microenvironment and the survival prognosis of patients. Models composed of multiple genes usually predict the survival prognosis of patients more accurately than single genes. We can analyze the multigene models that can predict the prognosis of COAD from the current database. Methods: The limma package of the R programming language is used for gene differential expression analysis. Kaplan-Meier curve is used to analyze the relationship between the patient risk score model and survival data. The hazard model is used to analyze the relationship between the risk score and the clinical data of COAD patients. The information of immune genes and immune cells is obtained from IMMPORT database and TIMER database. Receiver operating characteristic (ROC) curve is used to judge the stability of the model. Results: We found 7 immune genes, which can built a risk score model to predict the survival prognosis of COAD. According to univariate and multivariate analysis, the risk score can be used as an independent predictor. The content of some immune microenvironment cells will also increase as the risk score increases. Conclusions: We found 7 immune genes, such as SLC10A2 (solute carrier family 10 member 2), CXCL3 (C-X-C motif chemokine ligand 3), IGHV5-51 (immunoglobulin heavy variable 5-51), INHBA (inhibin subunit beta A), STC1 (stanniocalcin 1), UCN (urocortin), and OXTR (oxytocin receptor), can constitute a model for predicting the prognosis of COAD. They may provide potential therapeutic targets for clinical treatment of COAD.

Background: Tumor immunotherapy can not only eliminate the primary lesion, but also produce long-term immune memory, effectively inhibiting tumor metastasis and recurrence. However, immunotherapy also showed plenty of limitations in clinical practice. In recent years, the combination of nanomaterials and immunotherapy has brought new light for completely eliminating tumors with its fabulous anti-tumor effects and negligible side effects. Methods: The Core Collection of Web of Science (WOSCC) was used to retrieve and obtain relevant literatures on antitumor nano-immunotherapy since the establishment of the WOSCC. Bibliometrix, VOSviewer, CiteSpace, GraphPad Prism, and Excel were adopted to perform statistical analysis and visualization. The annual output, active institutions, core journals, main authors, keywords, major countries, key documents, and impact factor of the included journals were evaluated. Results: A total of 443 related studies were enrolled from 2004 to 2022, and the annual growth rate of articles reached an astonishing 16.85%. The leading countries in terms of number of publications were China and the United States. Journal of Controlled Release, Biomaterials, Acta Biomaterialia, Theranostics, Advanced Materials, and ACS Nano were core journals publishing high-quality literature on the latest advances in the field. Articles focused on dendritic cells and drug delivery accounted for a large percentage in this field. Key words such as regulatory T cells, tumor microenvironment, immune checkpoint blockade, drug delivery, photodynamic therapy, photothermal therapy, tumor-associated macrophages were among the hottest themes with high maturity. Dendritic cells, vaccine, and T cells tend to become the popular and emerging research topics in the future. Conclusions: The combined treatment of nanomaterials and antitumor immunotherapy, namely antitumor nano-immunotherapy has been paid increasing attention. Antitumor nano-immunotherapy is undergoing a transition from simple to complex, from phenotype to mechanism. Graphical