Periodontal disease is one of the most common diseases worldwide. It has a significant impact on oral health and subsequently the individual's quality of life. However, optimal regeneration of periodontal tissues, using current treatments, has yet to be achieved. Peptide self-assembly has provided a step-change in nanobiotechnology and regenerative medicine fields. Our aim was to investigate the effects of a selfassembling peptide (SAP; P 11-4) on periodontal regeneration in a preclinical model. Twenty-six bilateral maxillary critical-sized periodontal defects were created surgically in 13 rats. Defects on one side of the mouth were filled with P 11-4 hydrogel; the contralateral defect was untreated (control). Rats were sacrificed immediately post-surgery (time 0) and after 2 and 4 weeks. Retrieved maxillae were processed for histological, immunohistochemical, and histomorphometric assessments. The results of histological analysis showed greater organization of periodontal fibers in defects treated with P 11-4, at both time points, when compared to untreated defects. Histomorphometry showed that treated defects had both a significant increase in functional periodontal ligament length and a reduction in epithelial down growth after 4 weeks. At 2 weeks, treated defects showed a significant increase in expression of osteocalcin and osteoprotegerin as judged by immunohistochemistry. Also, a significantly higher osteoprotegerin/RANKL ratio was shown in treated defects. In conclusion, the results demonstrated enhanced regeneration of periodontal tissues when SAP P 11-4 was used to fill periodontal defects in rats. The findings of this study suggest that SAP P 11-4 is a promising novel candidate for periodontal regenerative therapy. Further investigations are required for optimization before clinical use.
Background Cancer initiation typically occurs when a proto-oncogene’s coding region undergoes mutation, resulting in uncontrollable cell growth and division, or when a tumour suppressor gene’s coding region is affected by a mutation that inhibits activity of the resulting gene product. The pathophysiologic result is, respectively, exaggerated cell-cycle growth or deficient programmed cell death. Osteopontin (opn) is an integrin-binding phosphoprotein that is expressed on the surface of normal cells. Osteopontin has a major role in diverse tumour components, especially those implicated in invasion and metastasis. In the present study, we aimed to illustrate the value of opn as a possible contributor in breast cancer (bca). Methods This prospective study included 115 patients newly diagnosed with bca and distant metastasis who were recruited from the Oncology Center, Mansoura University, and the Department of Clinical Oncology and Nuclear Medicine, Mansoura University Hospital, Egypt. The patients recruited had been diagnosed with disseminated visceral metastasis (visceral crisis), with or without bone metastasis; patients with cranial metastasis were excluded from the study. All patients received first-line chemotherapy with docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 or carboplatin 6 auc (area under the curve) on day 1 every 21 days for a maximum of 6 cycles or till development of toxicity. Trastuzumab (in cases of her2-positive disease) was given whenever possible (if government assistance or personal finances permitted). Serum levels of opn were assessed by enzyme-linked immunosorbent assay (elisa) before treatment was started. A group of 30 matched healthy women whose median serum opn level was 15 ng/dL were included, and that level was therefore defined as the cut-off value. In addition, opn gene mutation was determined by polymerase chain reaction (pcr). Correlations of pretreatment serum opn and opn gene mutation with various patient clinicopathologic criteria, response to the treatment, progression-free survival (pfs), and overall survival (os) were assessed. Results Mean serum opn was highest in her2-amplified bca (64.4 ± 42.3 ng/dL), and then in triple-negative bca (55.9 ± 34.7 ng/dL), followed by the luminal B and A subtypes (38.4 ± 33.1 ng/dL and 36.3 ± 32.2 ng/dL respectively, p = 0.017). Testing by pcr revealed that opn gene mutation was highest in triple-negative bca (85% opn mutant vs. 15% non-mutant), and then in her2-overexpressed bca (80% opn mutant vs. 20% non-mutant), followed by luminal B bca (61.9% opn mutant vs. 38.1% non-mutant); the least expression was detected in luminal A bca (57.9% opn mutant vs. 42.1% non-mutant). Interestingly, patients with high serum opn and opn gene mutation experienced both poor pfs (median: 12 months vs. 14 months; p = 0.001) and poor os (median: 14 months vs. 18 months; p = 0.001). Moreover, participants with opn gene mutation experienced a poor response: of those with progressive disease, 74% had opn mutation and 26% had unmutated opn (p = 0.04). Additionally, high pretreatment serum opn was correlated with poor treatment response: 49.1 ± 33.8 ng/dL in patients with progressive disease and 35.5 ± 34.3 ng/dL in those who achieved a complete response, a partial response, or stable disease (p = 0.05). Strong concordance was found between high serum opn and opn gene mutation in 69 tumours (79.3%), and strong concordance was detected between normal or low serum opn and non-mutant opn in 28 tumours (60.8%). Conclusions The current prospective work helps to highlight opn as a valid prognostic biomarker for patients with metastatic bca and reveals that high pretreatment serum opn and opn gene mutation are both strongly linked with poor response and survival. Concordance between elisa and pcr results indicates that either method can be used for the evaluation of opn. Increased opn gene mutation in triple-negative bca could assist in tailoring the treatment response in this very aggressive tumour subtype and could be considered a targetable molecule in future studies.
a b s t r a c tAims: To evaluate the therapeutic efficacy of azithromycin (azm) and/or metronidazole (mtz) on the histopathological features of rats' gingival overgrowth (GO) induced by cyclosporine-A (CsA) in an animal model. Methods:Ninety male albino rats were divided randomly into six equal groups. The rats of group I received corn oil via gastric feeding for 7 weeks. Group II rats were administered CsA for the same period. Groups III, IV, and V rats received CsA for 6 weeks and simultaneously in the 7th week received a monotherapy of placebo gel, azm suspension, mtz gel, respectively.Group VI rats were handled as groups III, IV, and V and instead received a combined therapy of azm suspension, and mtz gel. Rats were euthanized at the end of the experiment and routine tissue processing was carried out. The obtained specimens were stained with H&E, TGF-b, MMP-1, and IL-6 antibodies.Results: One-way MANOVA test for TGF-b, MMP-1, and IL-6 revealed an overall significant difference between the different groups (P = 0.000). LSD post hoc test for multiple comparisons of TGF-b revealed nonsignificant difference between groups I and VI and between groups IV and V. Nonsignificant difference was found between groups II and III considering the amount of MMP-1 immune expression. In addition, nonsignificant difference was found between groups V and VI regarding the amount of immune expression for IL-6.
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