J. Mol. Pathol., Volume 6, Issue 4 (December 2025) – 2 articles

Background: The aim of this study was to determine Ezrin and MMP-2 immunohistochemical expressions in the gingival tissue of patients with or without diabetes and to determine the role of the molecular pattern involvement in the evolution of periodontal disease. Material and Methods: In this histological study, we investigated 53 subjects with periodontal disease (test group—27 patients with type 2 DM; control—26 patients without diabetes). Samples from both groups were subjected to the immunohistochemistry (IHC) technique to evaluate the immunoreactivity (IR) intensity of Ezrin and MMP-2. Results: Among diabetic patients with periodontitis, 55.4% of patients exhibited intensely positive expression (+++) of Ezrin, and 44.6% of patients showed moderate expression (++) of Ezrin. All patients with diabetes and periodontitis showed intensely positive expression for MMP-2. In contrast, the control group showed negative expressions of Ezrin and MMP-2 (-) in 100% of cases. Significant statistical differences were found between Ezrin and MMP-2 expression in gingival samples of diabetic patients and non-diabetic patients with periodontal disease (p < 0.05). Conclusions: Ezrin and MMP-2 are significantly overexpressed in patients with diabetes and stage 2–3 periodontitis compared with non-diabetic patients with periodontal disease. Ezrin showed an exclusive pattern of moderate to strong positive staining in the diabetes–periodontitis group and complete absence in controls. MMP-2 displayed a broader range of staining intensities, with a predominance of strong positivity in all locations. Ezrin may represent a more consistent discriminative marker, whereas MMP-2 reflects a wider spectrum of tissue activation related to inflammation and tissue remodeling. Full article

Hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors, clinically established for treating renal anemia, are emerging as potent immunomodulators with therapeutic potential far beyond erythropoiesis. This review dissects the mechanistic basis of their action, centered on the stabilization of hypoxia-inducible factor-alpha (HIF-α), a master transcription factor that orchestrates fundamental shifts in immune cell function. We synthesize evidence showing how HIF-α stabilization alters innate immunity, recalibrates T- and B-cell responses, and reshapes inflammatory signaling. This activity translates to significant efficacy in preclinical models of autoimmune disorders, organ fibrosis, and ischemia–reperfusion injury. However, their broader clinical translation is hindered by a critical paradox in oncology. While HIF-α can potentiate anti-tumor immunity, its sustained activation risks promoting malignancy by driving angiogenesis, metabolic reprogramming, and fostering an immunosuppressive tumor microenvironment. Addressing this duality, alongside the potential for long-term immune dysregulation, is paramount. Future development must therefore prioritize precision-targeting strategies to harness the therapeutic benefits of HIF-PHD inhibitors while mitigating their pro-tumorigenic liabilities. Full article