CXCL14 and miR-4484 serves as potential salivary biomarkers for early detection of peri-implantitis.

Peri-implantitis develops in 43.3% of implant patients, which affects tissues around the implant that may ultimately cause implant loss if not treated properly. Due to difficulties in detecting peri-implantitis in its early phases, implant failures are constantly on the rise. Therefore, new specific molecular markers need to be identified to prevent or limit disease progression in peri-implantitis patients. We investigated levels of CXCL9, CXCL12, and CXCL14 in saliva samples of 45 patients with commercially pure grade 4/5 Titanium-Aluminum-Vanadium implants. We analyzed the correlation of the chemokine levels using Pearson's Correlation test and investigated their power to discriminate peri-implantitis vs. non-peri-implantitis patients using receiver operating characteristic analysis. Our in silico investigation revealed CXCL9, CXCL12, and CXCL14 as predicted targets of miR-4484, which has been demonstrated as a powerful biomarker candidate for early detection of peri-implantitis in our previous study. We measured high CXCL9 and low CXCL14 levels in the saliva of peri-implantitis patients. We also reported that the CXCL14 level showed a significant positive correlation with miR-4484. Besides, CXCL14 together with miR-4484 in saliva differentiated peri-implantitis patients from non-peri-implantitis individuals with 100% success. We offer differential expressions of CXCL14 and miR-4484 in the saliva of patients with peri-implantitis as potential salivary biomarkers for early detection of this disease.

Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1,2,4-triazole, and assessment of their anticancer activity.

A series of biologically active novel Mannich bases containing with a 1H-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases (S1-5) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel N-Mannich bases (M1-5) via the Mannich reaction. The structures of the compounds (M1-5) were determined structurally employing 1H/13C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds (M1-5) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound (M3) possesses a significant anticancer feature against FaDu cells that might be evaluated with further in vitro and in vivo studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds (M1-5). The docking score parameter of the compound (M3) against the 2DO4 protein is -5.67, the docking score parameter against the 5JPZ protein is -5.72, and finally, the docking score parameter against the 2H80 protein is -5.50. Molecular dynamic calculations are made for 0-100 ns. The ADME/T calculations were performed to find the drug potential of the compounds (M1-5). The results suggest that our drug candidate compound exhibits strong potential for co-administration with the antigen structures, owing to the low rate of interactions that decreased over time.Communicated by Ramaswamy H. Sarma.

MiR-4484 Acts as a Potential Saliva Biomarker for Early Detection of Peri-implantitis.

PURPOSE: Peri-implantitis, a potentially progressive disease that occurs in patients with dental implants, is more aggressive than periodontal lesions, which makes the prevention of peri-implantitis an important priority. Due to problems in the early detection of peri-implantitis, there is an urgent need for discovering novel biologic molecules with the ability of early diagnosis. The goal of this study was to profile the microRNA content of saliva samples collected from patients with titanium-aluminum-vanadium alloy dental implants who experienced peri-implantitis and to find potential diagnostic markers for detection of this disease. MATERIALS AND METHODS: The microRNA expression profiles of eight saliva samples (four collected from patients with peri-implantitis, four collected from patients who have successful implants) were investigated, and the deregulation of select microRNAs was further confirmed using quantitative polymerase chain reaction. RESULTS: The expressions of 179 microRNAs were found as deregulated in the saliva of peri-implantitis patients in comparison to controls. Then, downregulation of miR-4484 was confirmed in the saliva of peri-implantitis patients in a larger validation cohort. Also, 40% of non-peri-implantitis patients and 78% of peri-implantitis patients had significantly decreased miR-4484 expression in saliva samples collected after 4 to 6 months subsequent to implant placement compared with samples collected before implant placement. CONCLUSION: Considering these findings, microRNA content of saliva might be proposed as a plausible source for the early diagnosis of peri-implantitis, where miR-4484 might serve as an encouraging early diagnostic biomarker.

MicroRNA-145 transcriptionally regulates Semaphorin 3A expression in prostate cancer cells.

Prostate cancer (PCa) is one of the most prevalent cancer types among males. Differential expression of microRNAs is associated with various cancers including PCa. Although mature microRNAs are preferentially located in the cytoplasm, several studies identified mature human microRNAs in purified nuclei and miR-145 has been found to be predominantly expressed in the nuclei of benign tissues compared to tumor lesions. However, the nuclear functions of miR-145 are yet limited. Here, we aimed at investigating the inductive role of miR-145 on the expression of Semaphorin 3A (SEMA3A) in PCa cell lines. To study the regulatory potential of miR-145 in the transcriptional level in PCa, we overexpressed miR-145 in PC3 and DU145 cells, and confirmed its upregulation by quantitative-real-time-PCR. Then we investigated the tumor suppressor potential of miR-145 upon inducing SEMA3A expression using cell viability assay, western blot analysis, Chromatin Immunoprecipitation assay and luciferase reporter assay. Our results revealed that p53, miR-145, and SEMA3A expressions are significantly downregulated in PC3 and DU145 cells compared to nontumorigenic prostate epithelial PNT1a cells. miR-145 overexpression in PCa cells induced the expression of SEMA3A at both messenger RNA and protein levels. Furthermore, increased miR-145 expression enriched RNA Pol-II antibody on the promoter of SEMA3A and induced luciferase activity controlled by SEMA3A promoter. In this study, we showed that the functions of miR-145 are not limited to gene silencing, and found that it may lead to changes in gene expression in the transcriptional level.

Mode of action of carboplatin via activating p53/miR-145 axis in head and neck cancers.

OBJECTIVES: In this study, we aimed at investigating the expressions of miR-145 and its well-characterized direct targets on carboplatin treatment. STUDY DESIGN: Laboratory study. METHODS: The effect of carboplatin and miR-145 on the proliferative capacity of head and neck squamous cell carcinoma cells was evaluated using Cell Viability Detection Kit-8. Expressions of miR-145 and its targets were evaluated using quantitative real-time polymerase chain reaction on carboplatin treatment and p53 inhibition. Western blot was used to measure the levels of p53 and its acetylated versions in cells treated with carboplatin and/or pifithrin-α. RESULTS: We demonstrated that carboplatin induced the expression of miR-145 in a dose-dependent manner and suppressed the expressions of miR-145 direct targets. In addition, we showed that inhibition of p53 by pifithrin-α in carboplatin-treated cells reduced miR-145 expression and reversed the suppression of miR-145 direct targets. CONCLUSIONS: Considering all these findings together, one of the proposed mechanisms of carboplatin to kill cells might be the induction of miR-145 and deregulation of its targets in parallel, via p53 activation, which happens through carboplatin's DNA-damaging property. To the best of our knowledge, these findings are the first to reveal the relationship between carboplatin and miR-145 in cancer cells. LEVEL OF EVIDENCE: NA Laryngoscope, 2019.

ING5 inhibits cancer aggressiveness by inhibiting Akt and activating p53 in prostate cancer.

Prostate cancer (PCa) is one of the most common types of cancer in men. In several recent studies, chromosomal deletions in the q arm of chromosome 2, where ING5 resides within, have been identified in various cancer types including PCa. In this study, we investigate the role of ING5 as a tumor suppressor in PCa. We examined the expression level of ING5 in tissue samples and cell lines using quantitative real-time polymerase chain reaction and western blot analysis. We tested the in vitro tumor suppressor potential of ING5 in PC3 and LNCaP cells stably overexpressing it using cell viability, colony formation, migration, invasion, and apoptosis assays. We then investigated the effects of ING5 on the Akt and p53 signaling using western blot analysis. We show that ING5 is significantly downregulated in PCa tumor tissue samples and cell lines compared with the corresponding controls. In vitro assays demonstrate that ING5 effectively suppresses proliferative, clonogenic, migratory, and invasive potential and induce apoptosis in PCa cells. ING5 may potentially exert its anti-tumor potential by inhibiting AKT and inducing p53 signaling pathways. Our findings demonstrate that ING5 possesses tumor suppressor roles in vitro, pointing its importance during the prostatic carcinogenesis processes.