As two pivotal regulatory factors in cancer biology, oxidative stress and inflammation interact dynamically through complex network mechanisms to influence tumor initiation, progression, and treatment resistance. Oxidative stress induces genomic instability, oncogenic signaling activation, and tumor microenvironment (TME) remodeling via the abnormal accumulation of reactive oxygen species (ROS) or reactive nitrogen species (RNS). Conversely, inflammation sustains malignant phenotypes by releasing pro-inflammatory cytokines and chemokines and promoting immune cell infiltration. These processes create a vicious cycle via positive feedback loops whereby oxidative stress initiates inflammatory signaling, while the inflammatory milieu further amplifies ROS/RNS production, collectively promoting proliferation, migration, angiogenesis, drug resistance, and immune evasion in tumor cells. Moreover, their crosstalk modulates DNA damage repair, metabolic reprogramming, and drug efflux pump activity, significantly impacting the sensitivity of cancer cells to chemotherapy, radiotherapy, and targeted therapies. This review systematically discusses these advances and the molecular mechanisms underlying the interplay between oxidative stress and inflammation in cancer biology. It also explores their potential as diagnostic biomarkers and prognostic indicators and highlights novel therapeutic strategies targeting the oxidative stress–inflammation axis. The goal is to provide a theoretical framework and translational roadmap for developing synergistic anti-tumor therapies.

Background: Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Although marker genes associated with CRC have been identified previously, only a few have fulfilled the therapeutic demand. Therefore, based on differentially expressed genes (DEGs), this study aimed to establish a promising and valuable signature model to diagnose CRC and predict patient’s prognosis. Methods: The key genes were screened from DEGs to establish a multiscale embedded gene co-expression network, protein-protein interaction network, and survival analysis. A support vector machine (SVM) diagnostic model was constructed by a supervised classification algorithm. Univariate Cox analysis was performed to construct two prognostic signatures for overall survival and disease-free survival by Kaplan–Meier analysis, respectively. Independent clinical prognostic indicators were identified, followed by univariable and multivariable Cox analysis. GSEA was used to evaluate the gene enrichment analysis and CIBERSORT was used to estimate the immune cell infiltration. Finally, key genes were validated by qPCR and IHC. Results: In this study, four key genes (DKC1, FLNA, CSE1L and NSUN5) were screened. The SVM diagnostic model, consisting of 4-gene signature, showed a good performance for the diagnostic (AUC = 0.9956). Meanwhile, the four-gene signature was also used to construct a risk score prognostic model for disease-free survival (DFS) and overall survival (OS), and the results indicated that the prognostic model performed best in predicting the DFS and OS of CRC patients. The risk score was validated as an independent prognostic factor to exhibit the accurate survival prediction for OS according to the independent prognostic value. Furthermore, immune cell infiltration analysis demonstrated that the high-risk group had a higher proportion of macrophages M0, and T cells CD4 memory resting was significantly higher in the low-risk group than in the high-risk group. In addition, functional analysis indicated that WNT and other four cancer-related signaling pathways were the most significantly enriched pathways in the high-risk group. Finally, qRT-PCR and IHC results demonstrated that the high expression of DKC1, CSE1L and NSUN5, and the low expression of FLNA were risk factors of CRC patients with a poor prognosis. Conclusion: In this study, diagnosis and prognosis models were constructed based on the screened genes of DKC1, FLNA, CSE1L and NSUN5. The four-gene signature exhibited an excellent ability in CRC diagnosis and prognostic prediction. Our study supported and highlighted that the four-gene signature is conducive to better prognostic risk stratification and potential therapeutic targets for CRC patients.

Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. Metabolites and their sensors play an important role in the communication between gut microbes and their host. Our previous study revealed that G protein‐coupled receptor 35 (GPR35) is a key guardian of kynurenic acid (KA) and a core element of the defense responses against gut damage. However, the mechanism remains unknown. In this study, a DSS‐induced rat colitis model was established and 16S rRNA sequencing was applied to explore the influence of GPR35‐mediated KA sensing on gut microbiota homeostasis. Our results demonstrated that GPR35‐mediated KA sensing is a necessary component in maintaining gut barrier integrity against DSS‐induced damage. Furthermore, we provide compelling evidence suggesting that GPR35‐mediated KA sensing plays a crucial role in maintaining gut microbiota homeostasis, which contributes to alleviation of DSS‐induced colitis. In addition, five classes (Actinobacteria, Beta‐/Gamma‐proteobacteria, Erysipelotrichi, and Coriobacteriia) and six genera (Corynebacterium, Allobaculum, Parabacteroides, Sutterella, Shigella, and Xenorhabdus) were identified as the marked bacterial taxa that characterized the progression and outcome of colitis and are regulated by GPR35‐mediated KA sensing. Our findings highlight that GPR35‐mediated KA sensing is an essential defense mechanism against disorder of gut microbiota in UC. The results provide insights into the key role of specific metabolites and their monitor in maintaining gut homeostasis.

In this paper, two new iridium (III) complexes, [Ir(ppy)₂(ipbp)](PF₆) (Ir1) (ppy = 2-phenylpyridine, ipbp = 3-(1H-imidazo[4,5-f][1,10]phenanthrolin-2yl)-4H-chromen-4-one) and [Ir(bzq)₂(ipbp)](PF₆) (Ir2) (bzq = benzo[h]quinolone), were synthesized and characterized. The cytotoxicity of the complexes against human colon cancer HCT116 and normal LO2 cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The complexes Ir1 and Ir2 show high cytotoxic efficacy toward HCT116 cells with a low IC₅₀ value of 1.75 ± 0.10 and 6.12 ± 0.2 µM. Interestingly, Ir1 only kills cancer cells, not normal LO2 cells (IC₅₀ > 200 µM). The inhibition of cell proliferation and migration were investigated by multiple tumor spheroid (3D) and wound healing experiments. The cellular uptake was explored under a fluorescence microscope. The intracellular reactive oxygen species (ROS), change of mitochondrial membrane potential, glutathione (GSH) and adenine nucleoside triphosphate (ATP) were studied. Apoptosis and cell cycle arrest were performed by flow cytometry. The results show that the complexes induce early apoptosis and inhibit the cell proliferation at the G0/G1 phase. Additionally, the apoptotic mechanism was researched by Western blot analysis. The results obtained demonstrate that the complexes cause apoptosis in HCT116 cells through ROS-mediated mitochondrial dysfunction and the inhibition of PI3K/AKT signaling pathways.

Background: Epidemiologic studies continue to emphasize that increasing patients with inflammatory bowel disease (IBD) develop to colorectal cancer (CRC). Although the function and mechanisms of IBD-associated genes (IBDGs) in CRC tumorigenesis have been extensively researched, the implications of IBDGs in the prognosis value and tumor immunity of CRC remain unclear. Results: In this study, the expression, pathological stages and prognostic value of IBDGs in CRC were systematically analyzed, and 7 prognostic genes including CDH1, CCL11, HLA–DRA, NOS2, NAT2, TIMP1 and TP53 were screened through LASSO–Cox regression analysis. Then, a prognostic signature was established based on the 7 prognostic genes, and the model exhibited a good ability in risk stratification of CRC patients. Subsequent results showed that the genetic alterations of the 7 prognostic genes exhibited more significant and extensive influence on immune cells infiltration in colon adenocarcinoma than that in rectal adenocarcinoma. Meanwhile, immune cells infiltration also showed a significant difference between low-risk group and high-risk group. What’s more, 7 prognostic genes-based risk stratification was associated with microsatellite instability, and its prognostic characteristics were significantly negatively correlated with mismatch repair genes. Conclusions: This study provided a promising insight that the 7 IBDGs could be used as valuable biomarkers for prognostic diagnosis and personalized immunotherapy of CRC patients.

Background: Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. The metabolites and their sensors play an irreplaceable role in the communication of the gut microbes with their host. Our previous study revealed that G protein-coupled receptor 35 (GPR35) was a key guardian of kynurenic acid (KA) and a core element of the defense responses against gut damage. However, the mechanism remains unknown. Results: In this study, a DSS-induced rat UC model was established and 16S rRNA sequencing was applied to explore the influence of GPR35-mediated KA sensing on gut microbiota homeostasis. Our results demonstrated that GPR35-mediated KA sensing was a necessary component in maintaining gut barrier integrity against UC-induced gut damage. More importantly, we provided strong evidences to support that GPR35-mediated KA sensing played a crucial role in maintaining gut microbiota homeostasis, which contributed to alleviate DSS-induced UC. Moreover, 5 classes including Actinobacteria, Beta-/Gamma-proteobacteria, Erysipelotrichi and Coriobacteriia, and 6 genera including Corynebacterium, Allobaculum, Parabacteroides, Sutterella, Shigella and Xenorhabdus were identified as the marked bacterial taxa that characterized the progression and outcome of UC and regulated by GPR35-mediated KA sensing. Conclusion: Our findings highlight that GPR35-mediated KA sensing is an essential defense mechanism against the disorder of gut microbiota in UC. The results provide a profound insight in the key role of specific metabolites and their monitor in maintaining gut homeostasis.