(1) Background: The molecular mechanism of oxidative stress-related genes (OSRGs) in myocardial ischemia–reperfusion injury (MIRI) has not been fully elucidated. (2) Methods: Differential expression analysis, enrichment analysis, and PPI analysis were performed on the MIRI-related datasets GSE160516 and GSE61592 to find key pathways and hub genes. OSRGs were obtained from the Molecular Signatures Database (MSigDB). The expression pattern and time changes of them were studied on the basis of their raw expression data. Corresponding online databases were used to predict miRNAs, transcription factors (TFs), and therapeutic drugs targeting common differentially expressed OSRGs. These identified OSRGs were further verified in the external dataset GSE4105 and H9C2 cell hypoxia–reoxygenation (HR) model. (3) Results: A total of 134 DEGs of MIRI were identified which were enriched in the pathways of “immune response”, “inflammatory response”, “neutrophil chemotaxis”, “phagosome”, and “platelet activation”. Six hub genes and 12 common differentially expressed OSRGs were identified. A total of 168 miRNAs, 41 TFs, and 21 therapeutic drugs were predicted targeting these OSRGs. Lastly, the expression trends of Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 were confirmed in the external dataset and HR model. (4) Conclusions: Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 may be involved in the oxidative stress mechanism of MIRI, and the intervention of these genes may be a potential therapeutic strategy.

Glioma is the most prevalent and aggressive brain tumor with high recurrence rates and poor survival. Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, has emerged as a potential contributor to neurological diseases. However, whether P. gingivalis is present in glioma tissues and directly promotes malignant progression remains unclear. Here, immunohistochemistry the detected gingipain in 11 of 13 human glioma specimens, while fluorescence in situ hybridization further detected P. gingivalis-targeted 16S rRNA signals in 3 of 13 specimens. These findings support the presence of P. gingivalis-associated signals in human glioma tissues. In cellular models, P. gingivalis invaded glioblastoma cells and promoted cell proliferation, migration, and invasion through induction of mesenchymal transition and extracellular matrix remodeling, thereby accelerating glioma progression. In a mouse xenograft model, P. gingivalis inoculation enhanced tumor growth and was associated with changes in proliferation, mesenchymal transition, and ECM remodeling-related markers. Mechanistically, P. gingivalis activated the PI3K/AKT/mTOR signaling pathway, while pharmacological AKT inhibition (AKTi-1/2) effectively suppressed these tumor-promoting effects. Metronidazole treatment also reduced tumor growth in vivo. Collectively, these findings identify P. gingivalis as a potential microbial contributor to glioma malignant progression and support further investigation of host–microbe interactions and AKT signaling as potential avenues for therapeutic research.