ABSTRACT
Background: Mitogen-activated protein kinase 3 (MAPK3) mediates the onset, progression, metastasis, drug resistance, and poor prognosis in various malignancies, including glioma, liver, ovarian, thyroid, lung, breast, gastric, and oral cancers. Negative regulation of MAPK3 expression using miRNAs has led to therapeutic effects in cancer. Objectives: The present study performed molecular docking and dynamics simulation to identify potential MAPK3 inhibitors from natural flavonoids, possibly leading to drug development in cancer therapy. Methods: A computational drug discovery approach was performed using the AutoDock tool to identify potential MAPK3 inhibitors from 46 plant-based flavonoids. A cross-validation study was executed using the Schrödinger Maestro docking tool. Molecular dynamics (MD) was executed to evaluate the stability of docked poses between the top-ranked compounds and the MAPK3 catalytic domain. Interactions among the most potent MAPK3 inhibitors and residues within the receptor's active site were studied using the BIOVIA Discovery Studio Visualizer before and after 100 ns MD simulations. Results: Kaempferol 3-rutinoside-4'-glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2 exhibited a magnificent binding affinity to the receptor's active site. In addition, the stability of the docked poses of these compounds seemed to be stable after â¼45 ns computer simulations. Conclusion: The present study suggests that kaempferol 3-rutinoside-4'-glucoside, kaempferol 3-rutinoside-7-sophoroside, rutin, and vicenin-2 could strongly bind to the MAPK3 catalytic site and could be assigned as a potent inhibitor for MAPK3. These findings may be helpful in the treatment of various cancers. However, further validation experiments are needed.
ABSTRACT
BACKGROUND: Oral Lichen Planus (OLP) is a chronic autoimmune disease that could be considered as a potential premalignant status. OBJECTIVE: To evaluate the miRNA-146a and miRNA-155 expression levels in patients with oral Lichen planus lesions compared to healthy subjects with normal oral mucosa. METHODS: Forty patients with oral lichen planus and 18 healthy age and gender-matched controls were recruited in this case-control study. Oral lichen planus was diagnosed clinically and pathologically. The expression levels of two miRNAs in peripheral blood samples were determined using commercial TaqMan MicroRNA Assays. Relative quantification of gene expression was calculated by the 2-ΔΔct method. RESULTS: The expression levels of miRNA-146a and miRNA-155 in patients with oral Lichen planus were significantly higher than those of healthy controls. Also, a direct but insignificant correlation was found between miRNA-155 and miRNA-146a expression levels among the patient group. CONCLUSION: Our findings indicate that miRNA-146a and miRNA-155 could be potential biomarkers for the immunopathogenesis of oral lichen planus.
Subject(s)
Leukocytes, Mononuclear/physiology , Lichen Planus, Oral/genetics , MicroRNAs/genetics , Mouth Mucosa/physiology , Mouth Neoplasms/genetics , Precancerous Conditions/genetics , Adult , Biomarkers/metabolism , Case-Control Studies , Female , Follow-Up Studies , Gene Expression Regulation , Humans , Lichen Planus, Oral/diagnosis , Male , Mouth Neoplasms/diagnosis , Precancerous Conditions/diagnosisABSTRACT
BACKGROUND: Human immunodeficiency virus (HIV) affects lymphocytes, resulting in acquired immunodeficiency syndrome. Oxidative stress may play an important role in HIV pathogenesis. Melatonin has antioxidant, antiinflammatory and immunomodulatory effects. OBJECTIVE: The aim of this study was to evaluate salivary melatonin levels in HIV-positive patients and a healthy control group. METHODS: Forty-nine HIV-positive and 49 healthy subjects were included in this study. Patients' drug consumption and clinical examination results were registered in questionnaires. Unstimulated whole saliva was collected in the morning. The melatonin levels were measured by melatonin ELISA kits. Statistical analyses were performed with STATA 12, using t-test and chi-squared test. RESULTS: Salivary melatonin levels were significantly lower in the case group in comparison with the healthy control group (P=0.001). Age was significantly higher in the case group. Chi-squared test showed no statistically significant difference between the case and control groups in smoking (P=0.591) and addiction (P=0.204) but gender differences were observed (P=0.001). CONCLUSION: Salivary melatonin level as an antioxidant was lower in HIV-positive patients. Further studies are necessary to understand the exact role of melatonin in HIV-positive patients and its therapeutic effects.
