ANCIENT DNA RESEARCH : ONGOING CHALLENGES AND CONTRIBUTION TO MEDICAL SCIENCES

Life gave rise on our planet 3-4 billion years ago and since then, living organisms (from one cell to multicellular organisms) have undergone many genetic, phenotypic and communal changes. Scientists have been able to shed light on only a small part of this evolutionary process, but with the development of new techniques our knowledge is expanding day by day. For the past 30 years ancient DNA studies have aided us in understanding the molecular basis of the changes observed in living organisms. Ancient DNA (aDNA) is the genetic material obtained from biological remains (bones, teeth, plant seeds, etc.) acquired from archaeological and paleontological excavations. In the present review, molecular studies carried out to date, contributions of ancient DNA to medical sciences, as well as basic problems encountered in obtaining and using aDNA have been discussed

TESCALCIN OVER-EXPRESSION INCREASES KERATIN 18 AND 19 IN K562 CELLS

Purpose: Tescalcin (TESC) has been shown to be essential in mammalian cells as a regulator of intracellular Ca2+. Ca2+ is a second messenger functioning in many metabolic pathways as well as in cell differentiation, cell size and the cell cycle. K562 cells over-expressing TESC change their morphology and adopt adherent properties. Considering differences in morphology may have been reflected in changes of the cytoskeleton, we focused on the expression levels of keratins, which are cytoskeletal intermediate filaments in epithelial cells and also expressed in K562. We over-expressed the TESC gene via lentiviral transduction and analyzed keratin 8 (K8), keratin 18 (K18), and keratin 19 (K19) expression

THROUGH THE LOOKING GLASS: Real-Time Imaging in Brachypodium Roots and Osmotic Stress Analysis

To elucidate dynamic developmental processes in plants, live tissues and organs must be visualised frequently and for extended periods. The development of roots is studied at a cellular resolution not only to comprehend the basic processes fundamental to maintenance and pattern formation but also study stress tolerance adaptation in plants. Despite technological advancements, maintaining continuous access to samples and simultaneously preserving their morphological structures and physiological conditions without causing damage presents hindrances in the measurement, visualisation and analyses of growing organs including plant roots. We propose a preliminary system which integrates the optical real-time visualisation through light microscopy with a liquid culture which enables us to image at the tissue and cellular level horizontally growing Brachypodium roots every few minutes and up to 24 h. We describe a simple setup which can be used to track the growth of the root as it grows including the root tip growth and osmotic stress dynamics. We demonstrate the system’s capability to scale down the PEG-mediated osmotic stress analysis and collected data on gene expression under osmotic stress

Generation of an in vitro Intratumoral Heterogeneity Model by Lentiviral Fluorescent Labeling of Colon Cancer Cell Line DLD-1 Subclones

Purpose: Studying genomic changes during tumor progression has helped to understand the biology of many different cancers and has been the basis for targeted therapy strategies. However, resistance and differences in response to therapy in patients are still very important issues. One of the major underlying reasons is intratumoral cellular heterogeneity. Clones harbor mutations and/or epigenetic patterns providing a survival advantage under changing micro-environmental conditions are the main culprits of therapy resistance. Therefore, it is crucial to define and to study the properties and the contributions of these deviant subclones in vitro. In order to achieve that, we have generated a fluorescent intratumoral heterogeneity model of the colon cancer cell line DLD-1

Drug-Drug Interaction of Aldehyde Oxidase Inhibitor and Xanthine Oxidase Inhibitor with Favipiravir

Aim: Favipiravir is an effective antiviral used in the treatment of COVID-19. It is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug-drug interactions between favipiravir with both AO substrate and XO enzyme inhibitor, allopurinol, and an XO inhibitor, verapamil. Material and Methods: 25 Sprague-Dawley female rats, 250-300 g, were divided into five equal groups. Blood samples were taken from the jugular vein at the end of 0, 15, 30, and 45 minutes, and at the end of the 1st, 2nd, 4th, 6th, and 8th hours after the drugs were administered. The drug-blood concentration was determined in the HPLC-UV device using plasma. The ELISA method measured AO and XO enzyme activities in rat liver tissue. Results: Allopurinol prolonged the time taken for favipiravir to reach Cmax (Tmax), decreased maximum serum concentration (Cmax), elimination half-life (T1/2), area under the curve (AUC), and mean residence time (MRT). Allopurinol significantly reduced clearance per unit time (Cl/f) when co-administered with favipiravir. Verapamil accelerated the elimination of favipiravir, significantly reducing T1/2, MRT, and AUC. On the other hand, Favipiravir decreased the absorption of verapamil and slowed its elimination. Cmax, AUC, and Cl values of verapamil decreased. In addition, T1/2, MRT, and volume of distribution (Vd) increased. Conclusion: In conclusion, the concomitant use of favipiravir with other drugs that affect AO and/or XO enzyme activities may cause changes in the pharmacokinetic profiles of drugs and the levels of enzymes that metabolize drugs

18β-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice

Abstract The aim of the present study is to investigate the cardioprotective effects of 18β-glycyrrhetinic acid (18β -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18β-GA, and (4) 18β -GA+I/R. Ischemia was not applied to the sham and 18β-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18β-GA group, the mice were given 18β-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18β-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18β-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18β-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18β-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment