Aim
To investigate the association between root canal treatment outcome, diabetes mellitus, and alterations of the angiogenic process.
Methodology
A retrospective observational study was conducted in healthy (control group, CG) and diabetic (type II diabetes mellitus group, DG) patients after root canal treatment. The follow‐up appointments were performed to clinically and radiographically observe symptoms, the healing of periapical lesions and the quality of root fillings. In the animal model study, diabetic Goto‐Kakizaki (GK) rats and control Wistar rats were used. After 21 days of pulp exposure and the development of apical periodontitis (AP), the mandibles were removed for scintigraphic, radiographic, histopathological and molecular analyses. Chi‐square tests were performed to examine the variables related to endodontic outcome and differences between animal groups were assessed using the Student's t‐test.
Results
The group of patients with diabetes had a significantly lower rate of success following root canal treatment than the CG (p < .001). Logistic regression suggested that diabetes is a risk factor for success of root canal treatment. In the animal study, GK rats had significantly higher fasting glycaemia at t0 and t21 (p < .001) and triglycerides levels (p < .05) and area under the curve (AUC) during the insulin tolerance test at t21 (p < .001). AP area was significantly greater in GK rats (p < .05). Histologically, diabetic rats had increased signs of periodontal ligament inflammation 21 days after the induction of apical periodontitis, with fibro‐hyaline matrix filling and vessel with undefined walls. Wistar rats had significantly increased vascular endothelial growth factor (VEGF) levels and VEGF/Ang‐2 ratio 21 days after AP induction (p < .08; p < .07). GK rats had intrinsically lower levels of VEGF than control rats (p < .05), which did not change after AP.
Conclusion
Diabetes mellitus should be considered as an important factor in the prognosis of root canal treatment and its outcomes over time. Future strategies to improve angiogenesis and tissue repair should be pursued to achieve better root canal treatment outcomes in diabetic patients.
Notwithstanding the advances in the treatment of lung cancer with immune checkpoint inhibitors, the high percentage of non-responders supports the development of novel anticancer treatments. Herein, the expression of the onco-target nucleolin in patient-derived pulmonary carcinomas was characterized, along with the assessment of its potential as a therapeutic target. The clinical prognostic value of nucleolin for human pulmonary carcinomas was evaluated through data mining from the Cancer Genome Atlas project and immunohistochemical detection in human samples. Cell surface expression of nucleolin was evaluated by flow cytometry and subcellular fraction Western blotting in lung cancer cell lines. Nucleolin mRNA overexpression correlated with poor overall survival of lung adenocarcinoma cancer patients and further predicted the disease progression of both lung adenocarcinoma and squamous carcinoma. Furthermore, a third of the cases presented extra-nuclear expression, contrasting with the nucleolar pattern in non-malignant tissues. A two- to twelve-fold improvement in cytotoxicity, subsequent to internalization into the lung cancer cell lines of doxorubicin-loaded liposomes functionalized by the nucleolin-binding F3 peptide, was correlated with the nucleolin cell surface levels and the corresponding extent of cell binding. Overall, the results suggested nucleolin overexpression as a poor prognosis predictor and thus a target for therapeutic intervention in lung cancer.
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