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Background: NADPH oxidase 4 (NOX4) plays an important role in metabolic reprogramming, epithelial-mesenchymal transition (EMT), and other cellular processes by strictly regulating intracellular ROS generation. However, there is a lack of analysis on the role of NOX4 in the tumor immune microenvironment and predictive value for prognosis and immunotherapy response in various tumor types.
Methods: This study used data from the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Tumor Immune Single-cell Hub (TISCH), Genotype-Tissue Expression (GTEx), cBioPortal, Tumor Immune Estimation Resource (TIMER 2.0), and ROC Plotter databases to analyze the expression, prognosis, biological function, immune cell infiltration, and genetic and epigenetic changes of NOX4 in various tumor types. Meanwhile, in vitro experiments were conducted to verify the role of NOX4 in the migration, invasion, proliferation, and apoptosis of glioblastoma (GBM).
Results: The findings indicated that NOX4 is upregulated in various types of cancer, accompanied by gene amplification, mutation, and deletion. The high expression of NOX4 is associated with poor prognosis in various cancers. Functional enrichment analysis showed that NOX4 is mainly enriched in immune and cancer progression pathways, such as angiogenesis, EMT, interferon response, inflammatory response. Immune cell infiltration analysis showed that high expression of NOX4 is associated with increased infiltration of cancer-associated fibroblasts (CAF) and macrophages. In vitro experiments showed that silencing NOX4 inhibits the proliferation, migration, and invasion of GBM and increases cell apoptosis.
Conclusion: NOX4 can serve as a prognostic and immunotherapy response biomarker for various cancers and targeting NOX4 may be a feasible anti-tumor therapy and may have synergistic anti-tumor effects combined with immunotherapy.
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http://dx.doi.org/10.1016/j.intimp.2024.113815 | DOI Listing |
Nano Lett
September 2025
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.
View Article and Find Full Text PDFJAMA Netw Open
September 2025
Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla.
Importance: Janus kinase (JAK) inhibitors are highly effective medications for several immune-mediated inflammatory diseases (IMIDs). However, safety concerns have led to regulatory restrictions.
Objective: To compare the risk of adverse events with JAK inhibitors vs tumor necrosis factor (TNF) antagonists in patients with IMIDs in head-to-head comparative effectiveness studies.
Mol Biol Rep
September 2025
College of Animal Science and Technology, Shihezi University, Shihezi, 832003, China.
Background: A secondary Pasteurella multocida (Pm) infection following Mycoplasma ovipneumoniae (Mo) challenge in sheep results in severe respiratory disease. Scavenger receptor A (SRA) is a key phagocytic receptor on macrophages, which facilitates microbial clearance. However, the role of sheep SRA in Mo-associated secondary Pm infection is less understood.
View Article and Find Full Text PDFBiomater Sci
September 2025
Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.
Various cancer therapeutic strategies have been designed for targeting tumor-associated macrophages (TAMs), but TAM reprogramming-based monotherapy is often clinically hindered, likely due to the lack of a coordinated platform to initiate T cell-mediated immunity. Herein, we fabricated reactive oxygen species (ROS)-responsive human serum albumin (HSA)-based nanoparticles (PEG/IL12-IA NPs) consisting of indocyanine green (ICG), arginine (Arg), and interleukin 12 (IL12). Upon laser irradiation, the nanoparticles were found to be able to dissociate, thus facilitating the release of IL12.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Gastroenterology, Jinhua Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, China.
The fourth leading cause of cancer-related fatalities in the USA is pancreatic ductal adenocarcinoma (PDAC), a particularly deadly illness that is resistant to immunotherapy. One of the Main Obstacles in cancer research is developing better treatments for PDAC, which has the lowest 5-year survival rate of any malignancy. Anti-CTLA-4, anti-PD-L1, and anti-PD-1 immune checkpoint blockade medications also have poor results in these patients, which may indicate the presence of other immunosuppressive mechanisms in the pancreatic tumor microenvironment (TME).
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