Biomedical Research and Therapy 2022-01-22T21:16:35+00:00 Lili Hami Open Journal Systems Evaluation effects of ascorbic acid leads to activate and induce osteogenic protein marker expression: in silico and in-vitro study 2022-01-22T21:16:35+00:00 Imam Rosadi Feldiana Tuesrilia Indrady Karina Karina Nova Hariani <p><strong>Background</strong>: Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into several cell types including chondrocytes and osteocytes. The process of differentiation into such tissues is aided by transcription factors and collagen gene markers. Collagen biosynthesis is influenced by the presence of vascular endothelial growth factor (VEGF) and ascorbic acid cofactors of the prolyl hydroxylase 2 (PHD2) enzyme found in human cell receptors. The focus of this study is evaluation of how in silico methods can elucidate the effect of ascorbic acid on PHD2 and its expression. This study aimed to evaluate the role of ascorbic acid in its interaction with PHD2 (<em>in silico</em>) and the expression of type 1 collagen (COL1), type 2 collagen (COL2), and VEGF.</p> <p><strong>Methods</strong>: The technique of <em>in silico</em> molecular docking consisted of three steps: preparation of PHD2 receptors using AutoDock tools, preparation of ligand ascorbic acid using AutoDock tools, and molecular docking using AutoDock Vina. The results of in silico molecular docking were visualized using pyMOL and BIOVIA discovery studio. Furthermore, <em>in vitro</em> MSCs from adipose tissue were isolated and characterized based on protein marker expression. The effect of ascorbic acid supplementation (50 and 100 mg/mL) on stem cell differentiation was evaluated based on the mRNA ratio of <em>VEGF/COL1, VEGF/COL2</em>, and<em> COL2/COL1</em>.</p> <p><strong>Results</strong>: Molecular docking of ligand ascorbic acid with PHD2 resulted in nine poses. The third pose was chosen because it had an affinity of -5.7 kcal/mol and a root-mean-square deviation (RMSD) of 1.96, indicating a valid docking result. Meanwhile, the 2D conformer showed van der Waals bonds on Tyr303 and Try329 residues. MSCs were differentiated into adipocytes, chondrocytes, and osteocytes. Regarding the marker ratio of gene expression, at 50 mg/ml ascorbic acid there was an increase in the <em>VEGF/COL1</em> and <em>VEGF/COL2</em> ratios and a decrease in the<em> COL2/COL1</em> ratio compared with the control; at 100 mg/ml ascorbic acid there was a decrease in both ratios (<em>VEGF/COL1</em> and <em>COL2/COL1</em>), and the <em>VEGF/COL2</em> ratio continued to increase.</p> <p><strong>Conclusions</strong>: <em>In silico</em> molecular docking between PHD2 and ascorbic acid, which was studied via bioinformatics, resulted in a stable interaction with good ligand position. Further <em>in vitro</em> studies would support the influence of ascorbic acid on transcription factors, collagen gene markers, and the differentiation of MSCs.</p> 2022-01-22T21:10:53+00:00 ##submission.copyrightStatement## Mature Placental Teratoma: A Case Report 2022-01-22T09:50:58+00:00 Najmeh Nasiri Khormoji Vahid Soleimani Shahrzad Sheikhhasani <p><strong>Introduction</strong>: Placental teratoma is an uncommon, non-trophoblastic benign tumor. Since the first description of this type of tumor by Morvilli in 1925, only a few cases of this abnormality have been diagnosed and reported.</p> <p><strong>Case presentation</strong>: We describe here a 35-year-old pregnant woman admitted for an elective cesarean section. The placenta and membranes were delivered spontaneously. After delivering the placenta, a tumor mass containing hair was detected between the extraplacental amnion and chorion. On gross examination, a singleton placenta weighing 173 g, measuring 15 × 11 cm in area and 5.5 cm thick, with an attached cord and membranes, was observed. Microscopic examination showed orthokeratinized stratified squamous epithelium with underlying hair follicles, telangiectatic vessels, and sebaceous glands accompanied by subcutaneous fat. The fat also contained fibrocollagenous bundles. In addition, interconnecting bone trabecula rimmed by osteoblasts and attached mature cartilage were also found.</p> <p><strong>Conclusion</strong>: An awareness of placental teratoma from a pathological perspective is needed to include this anomaly in the differential diagnosis of benign placental nodules, obtain more information about this unusual lesion, and to conduct more studies on this prenatal abnormality.</p> 2022-01-22T09:47:55+00:00 ##submission.copyrightStatement## Long QT syndrome: Identification of a novel de novo mutation of calmodulin in a newborn girl 2022-01-22T12:45:12+00:00 Thi Huynh Nga Nguyen Chi Bao Bui Vuong Thao Vy Nguyen Manh Cong Nguyen Nguyen Thanh Tung Vu Minh Hiep Nguyen <p><strong>Background</strong>: Long QT syndrome (LQTS) is a genetically and phenotypically heterogeneous disorder of ventricular myocardial repolarization that is typically characterized by prolongation of the heart rate-corrected QT interval on a 12-lead electrocardiogram (ECG). LQTS has a complicated etiology since great genotypic and phenotypic overlapping among LQTSs limits the establishment of a diagnosis based solely on clinical features.</p> <p><strong>Case presentation</strong>: Here, we describe a Vietnamese newborn with a novel calmodulin (CALM2) variant. The patient was referred to the Department of Cardiology at Children's Hospital 2 in Ho Chi Minh City, Vietnam for multiple clinical cardiac presentations. The patient's family history was negative for cardiovascular diseases; however, she suffered from recurrent syncope and QT interval prolongation on resting in a 12-lead surface ECG. A fetal echocardiogram at 29 weeks detected signs of congenital heart disease. The newborn patient then suffered from sudden cardiac arrest and required cardiopulmonary resuscitation. Two weeks later, the patient suffered from torsade de pointes for the third time and required electrical shocks. An endotracheal tube was placed through the mouth into the trachea to facilitate breathing. Unfortunately, the patient expired at 3 months of age due to serious inflammatory issues. Whole exome sequencing (WES) — a technique used to determine variations in all coding regions (exons) of the known genes — validated a total of four rare variants in four cardiomyopathy (CM) genes, the CALM2, DSP, MYBPC3, and SPEG genes. We identified a novel de novo heterozygous missense mutation, c.280G &gt; T (p.Asp94Tyr), in the CALM2 gene (NM_001305626) encoding calmodulin, which is a ubiquitous calcium-binding protein that is important for a myriad of intracellular signaling events of cardiac function.</p> <p><strong>Conclusion</strong>: The results obtained in this study support the ``pan-cardiomyopathy panel'' approach, in which the molecular diagnosis of LQTS, the early identification of arrhythmia development, and the improved clinical management of cardiovascular disease patients are applied.</p> <p><strong>Trial registration</strong>: The procedures were reviewed and approved by the Ethical Committee of the University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam, under the number UMP-VN 2018-10a12.</p> 2022-01-22T12:45:12+00:00 ##submission.copyrightStatement##