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Interplay of hypoxia, angiogenesis, and macrophages in pulp and periapical lesions: an immunohistochemical cross-sectional study
Puja Chatterjee, Mala Kamboj, Shweta Mittal, Anjali Narwal, Anju Devi
J Korean Acad Conserv Dent ;Published online April 23, 2026
DOI: https://doi.org/10.5395/rde.2026.51.e22    [Epub ahead of print]
AbstractAbstract PDFPubReaderePub
Objectives
This study evaluated and correlated the immune expression of hypoxia and angiogenesis with macrophages in periapical granuloma (PG), radicular cyst (RC), and healthy pulp (HP).
Methods
An observational study was performed on 51 tissue blocks equally divided among the groups, stained immunohistochemically for hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and CD68, and the mean expression was calculated. Data were analyzed using Kruskal-Wallis, Mann-Whitney, Spearman correlation tests (p < 0.001), and multiple linear regression analysis (p ≤ 0.05).
Results
HIF-1α expression was highest in PG than RC and HP (p < 0.001). Significant differences were found between HP, PG, and RC (both p < 0.001). VEGF expression was highest in RC than in PG and HP (p < 0.001), with significant differences between HP and both PG and RC (p < 0.001); pairwise comparisons were significant between all groups (p < 0.001, p < 0.001, p = 0.018). Correlation analysis showed significant correlations between VEGF and CD68 in HP and PG (p = 0.007 and p = 0.028, respectively). Linear regression showed that study groups were significantly associated with mean scores of HIF-1α, VEGF, and CD68 (p = 0.002, p = 0.001, p < 0.001).
Conclusions
HIF-1α, VEGF, and CD68 showed increased expression in PGs and RCs, suggesting an association between hypoxic conditions, enhanced angiogenic activity, and macrophage presence within the periapical inflammatory microenvironment. Future studies exploring HIF-1α and VEGF inhibitors as potential treatment modalities for periapical lesions are warranted.
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High-plasticity mineral trioxide aggregate and its effects on M1 and M2 macrophage viability and adherence, phagocyte activity, production of reactive oxygen species, and cytokines
Betânia Canal Vasconcellos, Layara Cristine Tomaz Tavares, Danilo Couto da Silva, Francielen Oliveira Fonseca, Francine Benetti, Antônio Paulino Ribeiro Sobrinho, Warley Luciano Fonseca Tavares
Restor Dent Endod 2023;48(1):e6.   Published online December 29, 2022
DOI: https://doi.org/10.5395/rde.2023.48.e6
AbstractAbstract PDFPubReaderePub
Objectives

This study evaluated the effects of high-plasticity mineral trioxide aggregate (MTA-HP) on the activity of M1 and M2 macrophages, compared to white MTA (Angelus).

Materials and Methods

Peritoneal inflammatory M1 (from C57BL/6 mice) and M2 (from BALB/c mice) macrophages were cultured in the presence of the tested materials. Cell viability (MTT and trypan blue assays), adhesion, phagocytosis, reactive oxygen species (ROS) production, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β production were evaluated. Parametric analysis of variance and the non-parametric Kruskal-Wallis test were used. Results were considered significant when p < 0.05.

Results

The MTT assay revealed a significant decrease in M1 metabolism with MTA-HP at 24 hours, and with MTA and MTA-HP later. The trypan blue assay showed significantly fewer live M1 at 48 hours and live M2 at 48 and 72 hours with MTA-HP, compared to MTA. M1 and M2 adherence and phagocytosis showed no significant differences compared to control for both materials. Zymosan A stimulated ROS production by macrophages. In the absence of interferon-γ, TNF-α production by M1 did not significantly differ between groups. For M2, both materials showed higher TNF-α production in the presence of the stimulus, but without significant between-group differences. Likewise, TGF-β production by M1 and M2 macrophages was not significantly different between the groups.

Conclusions

M1 and M2 macrophages presented different viability in response to MTA and MTA-HP at different time points. Introducing a plasticizer into the MTA vehicle did not interfere with the activity of M1 and M2 macrophages.

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  • Local Immune Response to Mineral Trioxide Aggregate: A Narrative Review
    Shankargouda Patil, Shilpa Bhandi, Oladapo T Okareh
    World Journal of Dentistry.2023; 14(4): 382.     CrossRef
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Cytotoxicity of two self-adhesive resin cements and their interference in the phagocytic activity of murine macrophages
Danilo Couto da Silva, Leonardo Gomes Vaz, Warley Luciano Fonseca Tavares, Leda Quercia Vieira, Ricardo Reis de Oliveira, Antônio Paulino Ribeiro Sobrinho
Restor Dent Endod 2022;47(3):e31.   Published online July 14, 2022
DOI: https://doi.org/10.5395/rde.2022.47.e31
AbstractAbstract PDFPubReaderePub
Objectives

This study aimed to evaluate in vitro the effects of the self-adhesive resin cements RelyX U200 (3M ESPE) and seT PP (SDI Limited) on murine macrophages and the interference of the photoactivation.

Materials and Methods

Cell viability assays, cell adherence, yeast phagocytosis of Saccharomyces boulardii and production of reactive oxygen species (ROS) were performed in the presence of capillaries containing the respective self-adhesive cement when photoactivated or not.

Results

After long periods of contact, both types of cements, when not photoactivated, are more cytotoxic for macrophages. The seT PP cement when only chemically activated seems to interfere more negatively in the process of phagocytosis of yeasts S. boulardii. Both types of cements interfere in the cell adhesion process, independent of photoactivation. None of the types of cements tested was able to induce the production of ROS.

Conclusions

Our results highlight the great importance of the photoactivation of self-adhesive resin cements in the dental clinic, since RelyX U200, when photoactivated, presented the best results within the evaluated parameters.

Citations

Citations to this article as recorded by  
  • Influence of Preheating Self-Adhesive Cements on the Degree of Conversion, Cell Migration, and Cell Viability
    Henrique Cantarelli, Fernando Antonio Costa Xavier, Fernando Freitas Portella, Keiichi Hosaka, Eduardo Galia Reston, Louis Hardan, Rim Bourgi, Celso Afonso Klein-Junior
    Applied Mechanics.2024; 5(3): 553.     CrossRef
  • Dental Luting Cements: An Updated Comprehensive Review
    Artak Heboyan, Anna Vardanyan, Mohmed Isaqali Karobari, Anand Marya, Tatevik Avagyan, Hamid Tebyaniyan, Mohammed Mustafa, Dinesh Rokaya, Anna Avetisyan
    Molecules.2023; 28(4): 1619.     CrossRef
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  • 21 Download
  • 5 Web of Science
  • 2 Crossref
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