Category Archives: Uncategorized
Common mechanisms of placental dysfunction in preeclampsia, gestational diabetes, and COVID-19 in pregnant women
S. G. Vari1*, O. Shevchuk2, A. Boychuk3, S. Kramar4,
Z. Nebesna4, Y. Yakymchuk5, L. Kobylinska6, V. Chernyshenko7,
D. Korolova7, A. Gaspar-Suranyi8, T. Altorjay8, R. Gaspar9
1International Research and Innovation in Medicine Program, Cedars-Sinai Medical Center, Los Angeles, California, USA;
2Department of Pharmacology and Clinical Pharmacology, I. Horbachevsky Ternopil National Medical University, Ukraine;
3Department of Obstetrics and Gynecology, I. Horbachevsky Ternopil National Medical University, Ukraine;
4Department of Histology and Embryology, I. Horbachevsky Ternopil National Medical University, Ukraine;
5Department of Therapeutics and Family Medicine, I. Horbachevsky Ternopil National Medical University, Ukraine;
6Department of Biochemistry, Danylo Halytsky Lviv National Medical University, Ukraine;
7Department of Protein Structure and Function, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
8Department of Obstetrics and Gynecology, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
9Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
*e-mail: sandor.vari@cshs.org
Received: 13 June 2023; Revised: July 2023;
Accepted: July 2023; Available on-line: 11 July 2023
COVID-19 infection, preeclampsia and gestational diabetes mellitus in pregnancy cause similar changes in the placenta and influence development of the fetus between conception and birth in gestation. Proper uterine and placental vascularization is essential for normal fetal development. The transplacental exchange is regulated and maintained by the placental endothelium. During placental implantation, the trophoblast differentiates into two distinct layers, the inner cytotrophoblast and outer syncytiotrophoblast, which are key elements of the human placental barrier. Proinflammatory cytokines exacerbate ischemic events and create an upward spiral of an inflammatory reaction in the placenta. Placental pathology in gestational COVID-19 shows desquamation and damage of trophoblast and chronic histiocytic intervillositis. Similar lesions also occur in gestational diabetes mellitus and preeclampsia. The systemic inflammatory response of the mother, the increased inflammation in the placenta and cytokine production by placental trophoblasts should be monitored throughout pregnancy. Placental angiogenesis can be evaluated by serum vascular endothelial growth factor, Annexin A2, placental growth factor or sclerostin. Tissue damage can be assessed by measuring levels of serum lactate dehydrogenase and myeloperoxidase. Blood flow can be monitored with three-dimensional Doppler and pathological changes can be documented with paraffin-embedded tissue sections stained with hematoxylin and eosin, and electron microscope images as well as immunohistochemistry tests for vascular endothelial growth factor, placental growth factor, sclerostin and Annexin A2. The damage of maternal and fetal vascular perfusion (villitis and fibrin deposition) is a common mechanism of gestational diseases. The placenta lesions liberate anti-endothelial factors that lead to anti-angiogenic conditions and are the common mechanism of maternal placental vascular malperfusion in gestational diseases.
Healing Ukrainian Wounded Soldiers
Sandor G. Vari
International Research and Innovation in Medicine Program,
Cedars-Sinai Medical Center, Los Angeles, California, USA;
e-mail: sandor.vari@cshs.org
Received: 30 June 2023; Revised: 10 July 2023;
Accepted: 10 July 2023; Available on-line: 11 July 2023
The Regional Cooperation for Health, Science and Technology (RECOOP HST) Association, led by Cedars-Sinai Medical Center was formed in 2012 that includes 17 universities and academic organizations from eight countries in Central and Eastern Europe (Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, and Ukraine), and USA. The brutal Russian invasion of Ukraine changed the life of many families in Ukraine. The brave Ukrainian soldiers protecting their homeland, and now advancing into the occupied territories. During their heroic fight, many soldiers died, and many were wounded. RECOOP HST Association with Cedars Sinai Medical Center provided and provides continuous support for the wounded soldiers. RECOOP helped to purchase the electric gene¬rators at Lviv (LNMU), Ternopil (TNMU), and Kyiv (Palladin Institute), therefore, RECOOP donated 1,500 USD in humanitarian aid for each of our Ukrainian partners who have RECOOP Research Grants. RECOOP (350) and the author (200) purchased 550 one-handed Combat Application Tourniquet C-A-T® (30 USD/tourniquet) tested by U.S. Army’s Institute of Surgical Research and proved that C-A-T® completely occluded blood flow of an extremity in the event of a traumatic wound with significant hemorrhage. RECOOP already produced 2,400 Hemostatic Kits (9 USD/kit), and continuously producing the kits in Grant # 032: 2022–2023 Rostyslav Bilyy, Lviv, Ukraine, Improved Hemostatic Device with Chitosan Powder for Combat Injury Dressing. The Volunteer Centre of TNMU works around the clock to provide medical supplies and first aid kits for the Ukrainian soldiers and civilians distributing Hemostatic Kits and Combat Application Tourniquet C-A-T® to the frontline.
RECOOP HST Association with Cedars-Sinai Medical Center will start a project to help Ukrainian wounded soldiers. We would like to assist in the development of a grassroots organization of wounded soldiers and organize a network of Ukrainian medical universities. Ternopil National Medical University will assist in organizing the network to manage the Ukrainian Wounded Soldiers’ health problems online and offline. The posttraumatic stress disorder (PTSD) assessment will begin using a self-screen on the web. We will use the International Trauma Questionnaire (ITQ), an 18-question self-report measure focusing on the core features of PTSD and Complex PTSD (CPTSD). It was developed to be consistent with the organizing principles of the ICD-11 (https://novopsych.com.au/assessments/diagnosis/international-trauma-questionnaire-itq/). RECOOP Grant# 38 Ukrainian Wounded Soldier Project (UWSP) will involve volunteering wounded soldiers with PTSD would complete the online PTSD questionnaire that has already been tested in three Ukrainian projects [1 3]. We will train volunteer medical doctors to help the wounded soldiers online. Also, if the online consulting doctor realizes the severity of the health problems, soldiers should be referred to the nearby university hospital mental health unit. If you are interested in participating as a wounded soldier or medical professional, please contact Dr. Sandor G Vari, MD via Facebook Messenger or e-mail: vari@cshs.org.
Nobel prize winners Arvid Carlsson, Paul Greengard and Eric Kandel: the research of signal transduction in the nervous system
T. V. Danylova1,2*, S. V. Komisarenko3
1Institute of Social and Political Psychology, National Academy
of Educational Sciences of Ukraine, Kyiv;
2The Graduate School for Social Research, Institute of Philosophy
and Sociology of the Polish Academy of Sciences,Warsaw, Poland;
*e-mail: danilova_tv@ukr.net;
3Palladin Institute of Biochemistry, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: svk@biochem.kiev.ua
Received: 08 March 2023 2022; Revised: 11 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
For many decades, scientists have tried to unravel the mysteries of the nervous system – the complex phenomenon that receives messages, processes information, and sends signals to the rest of the body. The most important scientific discoveries of the 19th and the 20th centuries paved the way for the 2000 Nobel Prize in Physiology or Medicine awarded to Arvid Carlsson, Paul Greengard and Eric Kandel “for their discoveries concerning signal transduction in the nervous system”. So, the beginning of the new millennium was “marked” by pioneering research into the chemical transmission of signals in the central nervous system, which created the foundation for a deeper understanding of the mediatory role of dopamine, the processes of slow synaptic transmission, short-term and long-term memory, and the mechanisms of action of antipsychotic and antidepressant drugs. The paper aims to outline the main stages of scientific activities of a Swedish neuropharmacologist Per Arvid Emil Carlsson and the American neurobiologists Paul Greengard and Eric Richard Kandel.
Cyclic RGD-containing peptides: in silico exploration against BCL-X(L)
A. K. Oyebamiji1*, E. T. Akintayo1,2, C. O. Akintayo1,3*,
H. O. Aworinde4, O. D. Adekunle1, S. A. Akintelu5,6*
1Industrial Chemistry Programme, Bowen University, Iwo, Osun State, Nigeria;
*e-mail: abeloyebamiji@gmail.com;
2Department of Chemistry, Ekiti State University, Ado-Ekiti, Nigeria;
3Department of Chemistry, Federal University, Oye-Ekiti, Ekiti State, Nigeria;
*e-mail: cecilia.akintayo@bowen.edu.ng;
4College of Computing and Communication Studies, Bowen University, Iwo, Nigeria;
5School of Chemistry and Chemical Engineering,
Beijing Institute of Technology, Beijing, China;
6Department of Pure and Applied Chemistry, Ladoke Akintola University
of Technology, Ogbomoso, Oyo State, Nigeria;
*e-mail: akintelusundayadewale@gmail.com
Received: 08 March 2023; Revised: 28 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Сyclic peptides attract attention for possible applications in cancer treatment. We examined the ability of six cyclic RGD-containing peptides-based compounds to inhibit B-cell lymphoma-extra-large (Bcl-XL) (PDB ID: 3zk6) using the in silico method. We observed that the addition of electron withdrawing group (–Cl) to cyclic RGD-containing peptides-based compound induced a radical improvement in the hydrogen bond strength with Arg139 in Bcl-XL. Compound F with -9.2 kcal/mol was observed to be positioned at the best-docked site in the binding pocket of Bcl-XL and, therefore, suggested to have greater potential anticancer ability than other studied compounds as well as the referenced compound (Doxorubicin). The ADMET properties of compound F and Doxorubicin were investigated and reported. Our findings may open door for the design and development of library of efficient cyclic RGD-containing peptides-based drug-like compounds as potential anti- cancer agents.
Characterization of lectins from wheat seedlings infected with Fusarium graminearum and treated by jasmonic acid
O. О. Molodchenkova1*, O. V. Ryshchakova1,
T. V. Kartuzova1, L. T. Mishchenko2
1Plant Breeding and Genetics Institute – National Center of Seed
and Cultivar Investigation, Laboratory of Plant Biochemistry, Odesa, Ukraine;
*e-mail: olgamolod@ukr.net;
2ESC “Institute of Biology and Medicine”,
Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: lmishchenko@ukr.net
Received: 24 February 2023; Revised: 27 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Fusarium head blight is one of the most serious diseases of wheat caused by a range of Fusarium fungi, which infects the heads of the crop, reducing grain yield. Lectins that specifically bind carbohydrate ligands of various chemical nature and Jasmonic acid (JA) as a key regulator of plant development play an important role in plant protective responses to biotic factors. The goal of the study was to determine the activity and biochemical characteristics of soluble lectins in wheat seedlings of varieties ‘Lastivka odeska’ with a high resiliency to Fusarium graminearum and ‘Nikonia odeska’ susceptible to Fusarium graminearum. Wheat seedlings were grown on the media containing pathogenic infection or JA solution. Lectins were purified by affinity chromatography and separated by electrophoresis in 15% PAGE. Lectin activity was determined by the method of trypsinized blood erythrocytes hemagglutination. Molecular mass of the main components of lectins from ‘Lastivka odeska’ seedlings was determined to be 67, 60, 45 kDa, and of the main component of lectins from ‘Nikonia odeska’ seedlings – 45 kDa. Lectins isolated from the control untreated seedlings had preferential affinity for N-acetylglucosamine, D-galactosamine and D-fructose-6-phosphate. It was shown that both at pathogen action or JA treatment, lectin activity in the seedlings of resistant variety ‘Lastivka odeska’ was increased while in the seedlings of susceptible variety ‘Nikonia odeska’ it was decreased as compared to control. At the joint action of pathogen and JA, lectin activity in the seedlings of susceptible variety increased compared with the infected seedlings. The results obtained can be used for the development of biochemical methods for assessing the degree of wheat varieties resiliency to fusariose.
Dynamics of CD68 receptor expression in macrophages of the interstitial space of the rat testis under triptorelin prolonged administration
Ye. V. Stetsuk1*, V. I. Shepytko1, O. Ye. Akimov2,
N. V. Boruta1, M. V. Rud1, L. B. Pelypenko1, O. D. Lysachenko1,
O. V. Vilkhova1, T. A. Skotarenko1, O. V. Voloshyna1
1Department of Histology, Cytology and Embryology,
Poltava State Medical University, Poltava, Ukraine;
2Department of Pathophysiology, Poltava State Medical
University, Poltava, Ukraine;
*e-mail: Stetsuk78@gmail.com
Received: 18 May 2023; Revised: 01 June 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Testosterone, the production of which is stimulated by the release of luteinizing hormone (LH) has a remarkable anti-inflammatory and immunomodulatory effect, and in conditions of testosterone deficiency tissue damage can occur due to excessive differentiation of macrophages into a proinflammatory M1 phenotype. The aim of this study was to determine the spread of CD68 receptors as the marker of inflammation on the cells in the interstitial space and testicular vessels under LH synthesis blockade with tryptorelin. Sexually mature white male rats were randomly divided into control (10 animals) and experimental (25 animals) groups. Animals in the experimental group were injected with a tryptorelin acetate solution (0.3 mg/kg). Immunochemical analysis of CD68+ expression was estimated at Olympus FV10i-LIV laser scanning confocal microscope using fluorescent labeling dye. It was shown that luteinizing hormone deprivation led to an increase in the distribution of the CD68 receptor in the interstitial space and in the testicular vessels from day 30 to 180 of the experiment, associated with the increase of inducible NO synthase activity in testis tissue.
The effect of L-glutamic acid and N-acetylcysteine administration on biochemical blood parameters in rats treated with CCl(4)
N. O. Salyha
Institute of Animal Biology NAAS of Ukraine, Lviv;
е-mail: ynosyt@yahoo.com
Received: 30 March 2023; Revised: 19 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
A toxic organic substance CCl4 is a well known model compound for studying detoxification function of the liver and developing oxidative stress. The goal of the study was to estimate the effect of L-glutamic acid (L-Glu) and N-acetylcysteine (NAC) administration on rat blood parameters upon the toxic effects of CCl4. Experimental male Wistar rats were injected intraperitoneally with CCl4, the rats of CCl4/L‑Glu group were additionally injected with L-Glu (750 mg/kg), of CCl4/NAC group – with NAC (150 mg/kg), of CCl4/L-Glu/NAC group – with L-Glu (750 mg/kg) and NAC (150 mg/kg). The duration of the experiment was 24 h. Increased level of lipid peroxides, TBARS, triacylglycerols, cholesterol and decreased glutathione peroxidase, glutathione reductase, glutathione-S-transferase activity and GSH content were observed in the blood of the CCl4 treated animals compared to the control untreated group. When animals were additionally injected with L-Glu or L-Glu/NAC, the most of the studied indicators were shown to be close to the control level These results suggest that the mentioned above aminoacids attenuated CCl4-induced oxidative stress in the blood of rats.
Biochemical parameters of blood and tissue of the gastrocnemius muscle in chronically alcoholized rats under oral administration of C(60) fullerene aqueous solution
O. Motuziuk1,2, D. Nozdrenko2, S. Prylutska3,
K. Bogutska2, O. Korotkyi2, Yu. Prylutskyy2*
1Lesya Ukrainka Volyn National University, Lutsk, Ukraine;
2Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: prylut@ukr.net;
3National University of Life and Environmental Science of Ukraine, Kyiv
Received: 17 March 2023; Revised: 01 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Biochemical indices of blood and tissue of the gastrocnemius muscle chronically alcoholized (for 3, 6 and 9 months) rats were studied. С60 fullerene aqueous solution (C60FAS) was administered orally as a pharmacological agent at a dose of 1 mg/kg daily throughout the experiment in a three routes: 1 h before alcohol intake (preventive regimen), together with alcohol (therapeutic regimen I) and 1 h after alcohol intake (therapeutic regimen II). Creatine phosphokinase (CPK), lactate dehydrogenase (LDH), catalase, superoxide dismutase, glutathione peroxidase (GPx) activity and the level of creatinine, lactate, hydrogen peroxide, reduced glutathione were estimated with clinical diagnostic kits. A pronounced upward trend in creatinine and lactate content, CPK and LDH activity with increasing degree of alcoholic myopathy during experiment was detected. Administration of C60FAS was shown to reduce the biochemical indices of muscle injury and to reduce oxidative processes by maintaining the balance between pro-oxidant and antioxidant systems. The maximum positive effect was observed when C60FAS was administered together with alcohol (therapeutic regimen I). The results indicate on C60 fullerene ability to correct the pathological condition of the muscular system arising from alcohol intoxication.
Oxydative stress in type 2 diabetic patients: involvement of HIF-1 alpha AND mTOR genes expression
Y. A. Saenko1, O. O. Gonchar2*, I. M. Mankovska2,
T. I. Drevytska2, L. V. Bratus2, B. M. Mankovsky1,3
1SI “The Scientific and Practical Medical Center of Pediatric Cardiology and Cardiac Surgery
of the Ministry of Health of Ukraine”, Clinic for Adults, Kyiv;
2Department of Hypoxia, Bogomoletz Institute of Physiology,
National Academy of Sciences of Ukraine, Kyiv;
3Shupyk National Healthcare University of Ukraine, Kyiv;
*e-mail:olga.gonchar@i.ua
Received: 22 March 2023; Revised: 25 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
Biochemical and genetic mechanisms of oxidative stress (OS) developing in the blood of patients with type 2 Diabetes mellitus (T2DM) were studied. Twenty patients with T2DM and 10 healthy persons participated in this study. Lipid peroxidation, the content of protein carbonyls and H2O2 production were measured in blood plasma and erythrocytes as OS biomarkers. Activity of SOD, catalase, and GPx as well as reduced glutathionе (GSH) level in plasma and erythrocytes were estimated. The gene expression of key regulators of oxygen and metabolic homeostasis (HIF-1α and mTOR) in leukocytes were studied. It was found a significant rise in TBARS and protein carbonyls content in plasma as well as H2O2 production in erythrocytes from patients with T2DM compared to control. The diabetic patients also demonstrated an increase in the SOD and catalase activity in plasma and significantly lower GSH content and GPx activity in erythrocytes compared to the healthy participants. The established marked inhibition of mTOR gene expression and the tendency to an increase in HIF-1α gene expression in leukocytes of patients with T2DM may serve as a protective mechanism which counteracts OS developing and oxidative cell damage.
Vitamin D(3) and methylenebisphosphonic acid in the correction of mineral metabolism disorders and bone remodeling associated with glucocorticoid-induced osteoporosis
O. O. Lisakovska1*, I. O. Shymanskyi1, V. M. Vasylevska1,
E. P. Pasichna1, M. M. Veliky1, S. V. Komisarenko2
1Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
2Department of Molecular Immunology, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: o.lisakovskaya@gmail.com
Received: 03 April 2023; Revised: 27 April 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
The study was aimed at evaluating therapeutic efficacy of vitamin D3 (VD3, 1000 IU/kg of b.w., 30 days) and sodium salt of methylenebisphosphonic acid (MBPA, 17 mg/kg of b.w., 30 days) monotherapies as well as their effect in combination in preventing mineral metabolism and bone remodeling disturbances associated with glucocorticoid(GC)-induced osteoporosis. Osteoporosis in rats was induced by long-term (30 days) administration of the synthetic glucocorticoid prednisolone (5 mg/kg of b.w.). Calcium and inorganic phosphate levels, the activity of alkaline phosphatase (ALP) in serum, bone tissue and bone marrow were determined spectrophotometrically. The protein levels of VD3 receptor (VDR), receptor activator of nuclear factor kappa-B (RANK), its ligand (RANKL), and osteoprotegerin (OPG) in bone tissue were determined by Western blotting. Serum 25-hydroxyvitamin D3 (25OHD3) content was assayed by ELISA. It was shown that prednisolone caused the development of hypocalcemia and hypophosphatemia, increased the alkaline phosphatase activity in the blood serum, while downregulating its activity in bone tissue and bone marrow. GC-induced osteoporosis was accompanied by a profound deficiency of VD3 and a decrease in the content of VDR. Evaluation of the NF-κB-associated cytokine axis RANK/RANKL/OPG, which regulates the balance of osteoblasts/osteoclasts, showed a simultaneous decrease in the RANK content and OPG/RANKL ratio. Vitamin D3 restored mineral metabolism and 25OHD3 level that led to the normalization of VDR-mediated signaling and RANK/RANKL/OPG functions in bone tissue. It has been shown that the administration of MBPA had a corrective effect on the content of mineral components in the blood serum and bone tissue, as well as on the activity of alkaline phosphatase only in combination with vitamin D3, indicating a low efficiency of bisphosphonate monotherapy in GC-induced vitamin D3 deficiency and osteoporosis.