Tag Archives: inflammation
Inflammatory cytokines profile and oxidative stress markers in the serum of albino rats injected with macrophage migration inhibitory factor
N. T. Guliyeva1, S. V. Guliyeva2*, R. A. Akhundov2,
N. R. Jabbarova3, T. A. Eyvazov2
1Department of Cytology, Embryology and Histology,
Azerbaijan Medical University, Baku, Azerbaijan;
2Research Center, Azerbaijan Medical University, Baku, Azerbaijan;
3Department of Health Care Organization,
Azerbaijan Medical University, Baku, Azerbaijan;
*e-mail: quliyevasevda789@gmail.com
Received: 09 July 2025; Revised: 28 August 2025;
Accepted: 28 November 2025; Available on-line: 23 December 2025
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in the regulation of inflammation, immune responses, and redox homeostasis. However, its metabolic effects in experimental models remain insufficiently characterized. The aim of the work was to estimate the effect of recombinant MIF on cytokines profile, antioxidant defense markers and LPO indicators at different time points following its single intraperitoneal administration to albino rats. Animals were divided into a control group (n = 20) and three experimental groups (n = 10 each) assessed in 2, 3, and 14 days after MIF administration (10 µg/kg of b.w.), respectively. Serum samples were analyzed for IL-6, IL-10, TNF-α, IL-4, antioxidant markers and LPO products levels by ELISA and standard biochemical assays. It was shown that MIF administration induced time-dependent pro-inflammatory and pro-oxidant effects. Early compensatory anti-inflammatory responses were marked by increased IL-10 and decreased IL-6 levels. However, at the later stages (days 3 and 14), IL-6 and TNF-α elevation, along with IL-4 suppression, indicated a shift toward chronic inflammation. Antioxidant parameters progressively declined, with maximal suppression observed on day 14. Concurrently, a significant accumulation of LPO products confirmed sustained oxidative stress and membrane damage. These findings underscore the potential of MIF as a pharmacological target for the treatment of chronic inflammatory and metabolic disorders.
Scientific advancement on the way to molecular vitaminology at the Department of Vitamins and Coenzymes of the Palladin Institute of Biochemistry
M. Veliky, I. Shymanskyi, T. Kuchmerovska*, Yu. Parkhomenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Vitamins and Coenzymes, Kyiv;
*e-mail: tkuchmerovska@gmail.com
Received: 05 May 2025; Revised: 08 July 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025
Modern advances in molecular vitaminology are characterized by a marked expansion in understanding the molecular mechanisms underlying the actions of vitamins and their biologically active derivatives as highly effective compounds that ensure controlled interactions between cellular regulatory systems and metabolic processes. The molecular mechanisms of the pleiotropic effects of the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2D3), are realized in target tissues through vitamin D3 receptors (VDR), which are present in virtually all cells. Our studies have focused on VDR-mediated effects, including modulation of the transcriptional activity of NF-κB, NFAT, HIF-1 and PPAR, as well as involvement of regulatory pathways such as HIF-1α/VEGF and RANK/NF-κB. We have also examined signaling through glucocorticoid and mineralocorticoid receptors, which play a key role in the antioxidant, anti-inflammatory, and anti-apoptotic effects of vitamin D3 under normal conditions and in pathology (osteoporosis, neurodegenerative disorders associated with glucocorticoid-induced neurotoxicity and type 2 diabetes mellitus). The mechanisms of the neurotropic effects of vitamin B3 (nicotinamide) and a derivative of nicotinic and amino butyric acid, nicotinoil-GABA (N-GABA), have also been studied. It has been demonstrated that nicotinamide (NAm) inhibits the development of diabetic neuropathy by reducing the activity and level of the PARP-1 enzyme, suppressing its fragmentation and preventing DNA damage in the brain tissue, and normalizing the nuclear levels of SIRT1 and SIRT2 proteins in neurons. One of the effective methodological approaches in our studies has been the investigation of thiamine-binding proteins in the brain and the effects of thiamine deficiency on the expression and state of neurospecific proteins. Based on our findings, we have formulated a working hypothesis regarding the molecular mechanisms of vitamin B1 involvement in the functioning of the cholinergic component of the nervous system. This hypothesis suggests that, in addition to the pool of thiamine diphosphate (ThDP) that binds to ThDP-dependent enzymes, nerve cells contain a rapidly exchangeable pool of thiamine derivatives that are involved in acetylcholine metabolism. The research achievements of our Department demonstrate the therapeutic potential of vitamins D3, B3, B1, and their biologically active derivatives in preventing the development of neurodegenerative complications under various pathological conditions and provide a scientific basis for the development of novel vitamin supplements.
About the Department of Molecular Immunology, or why it is important to study immunological processes at the molecular level
S. V. Komisarenko, S. I. Romaniuk
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Molecular Immunology, Kyiv;
e-mail: svk@biochem.kiev.ua
Received: 2025; Revised: 2025; Accepted: 2025
This review summarizes the scientific accomplishments of the Department of Molecular Immunology at the Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine over the period 1975–2025. Particular attention is given to studies on the mechanisms and functions of nicotinic acetylcholine receptors (nAChRs) expressed in lymphocytes, focusing on their role in inflammatory processes, including those associated with Alzheimer’s disease, COVID-19 and post-COVID syndrome. The review also covers research on the mathematical modeling of interactions between polyreactive immunoglobulins (PRIGs) and antigens, as well as studies on the biological functions of these antibodies. Additionally, it examines the antigenic, immunogenic, and immunobiological properties of proteins – especially recombinant proteins – that could serve as key components of diagnostic test systems and next-generation vaccines for respiratory infectious diseases such as pertussis, diphtheria, tuberculosis and COVID-19. The article further considers opportunities to develop therapeutic agents based on recombinant proteins, including single-chain variable fragment (including scFv antibodies), vitamin complexes and other bioactive components for the treatment of human diseases. Special attention is also given to efforts aimed at disseminating knowledge on biosafety, bioprotection and bioethics in Ukraine. Finally, the review looks at future prospects for the Department of Molecular Immunology, in light of current challenges and new opportunities, particularly those arising from rapid advances in biotechnology.
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.
Inflammation is the common mechanism of diseases (CMD) in COVID-19 disease during pregnancy and in gestational diabetes mellitus
Sandor G. Vari
Cedars-Sinai Medical Center, International Research and Innovation in Medicine Program, Los Angeles, California, United States
The Regional Cooperation for Health, Science and Technology (RECOOP HST) Consortium, led by Cedars-Sinai Medical Center was formed in 2006, was transformed into an Association in 2012 and includes 17 universities and academic organizations from eight countries: seven in Central and Eastern Europe (Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, Ukraine) and the United States. RECOOP builds multinational, multidisciplinary collaborations, and assists as well as coordinates the research activities of the sixteen research groups that are the Cedars-Sinai Medical Center – RECOOP Research Centers (CRRCs). https://www.cedars-sinai.org/research/administration/recoop.html.
Implementations of RECOOP’s strategic goals enable diverse talents geared towards integration of new knowledge derived from multiple specialties to investigate Common Mechanism of Diseases (CMD). While some may consider RECOOP’s CMD research strategy unorthodox, recent and timely scientific evidence shows that inflammation is the triggering event in the change of vascularization and it is the common mechanism of these two diseases: COVID-19 Disease during pregnancy and gestational diabetes mellitus (GDM).
Binding of the SARS-CoV-2 virus to the ACE2 receptor and its entrance into endothelial cells plays a role in vascular thrombosis but has a lesser effect placental endothelial dysfunction. The latter is induced by inflammation and exacerbated by proinflammatory cytokines, resulting in ischemic events and creating an upward spiral of an inflammatory reaction in pregnant women, accompanied by similar conditions in the placenta that will ultimately affect fetal development. In mild or moderate COVID-19 disease, changes in placental vascularization and blood flow have similarities to comorbidities in pregnancy such as GDM. However, during severe or critical stages of COVID-19 Disease, the changes could be harsher than those observed in GDM.
In COVID-19 Disease and GDM the immune status of pregnant women and consequently the newborn is altered due to inflammation and characterized by changes in levels of C-reactive protein (CRP), immunoglobulins (IgG, IgM, IgA) and proinflammatory cytokines that are detectable in maternal and umbilical cord blood and in mother milk.
To examine changes and monitor placental angiogenesis it is necessary to measure Vascular Endothelial Growth Factor (VEGF), Placental Growth Factor (PLGF), and Umbilical Cord Blood Sclerostin (UCBS) in maternal and umbilical cord blood serum. The angiogenic activity of sclerostin must be validated with the well-known marker VEGF, which is a proven indicator for changes in vascularization. The morphology of the vascular tree and blood flow in the placenta could be evaluated with three-dimensional power Doppler. The proinflammatory and ischemic effects in the placenta should be quantified with histopathology and immunohistochemistry. Changes in blood flow in the placenta and the morphology of the vascular tree in COVID-19 Disease during pregnancy may have similarities to those observed in GDM.
In summary, to improve maternal and fetal outcomes it is imperative to formulate better strategies for managing pregnancies during COVID-19 Disease and comorbidities like GDM. VEGF, PLGF and UCBS could be predictors of placental weight, birth weight, and fetal outcomes. In addition, further studies are needed to investigate the effects, if any, of proinflammatory and anti-inflammatory cytokines on postnatal development.
Freezing influences, the exposure of IgG glycans in sera from multiple sclerosis patients
M. Bozhenko1, M. Boichuk1, G. Bila2, T. Nehrych1*, R. Bilyy2*
1Department of Neurology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2Department of Histology, Cytology and Embryology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
*e-mail: r.bilyy@gmail.com; tnehrych@gmail.com
Received: 08 January 2020; Accepted: 27 March 2020
N-glycan residues attached to Asn297 of the immunoglobulin IgG molecule are responsible for changing its structural conformation and are used as markers of many inflammatory diseases. Freezing stabilizes protein structure, while recent solution NMR data showed greatly altered IgG glycan mobility at different temperatures. The aim of the current work was to investigate whether freezing sera samples from multiple sclerosis (MS) patients and normal healthy donors (NHD) influences exposure of IgG glycans. The developed lectin immunosorbent assay was used to evaluate exposure of native IgG glycans with fucose-binding AAL lectin and sialic acid-binding SNA lectin. Sera samples were divided and either immediately frozen at -20 °C or stored at 4 °C. Lectin exposure was compared between 5 MS patient groups (n = 75) vs NHD (n = 23) and in paired samples with and without freezing. A significant increase in the exposure of fucose residues on IgG glycans in MS patients, compared to NHD, was observed. This increase was only observed if sera were frozen before analysis. The exposure of sialic acid was decreased in MS vs NHD samples after freezing sera samples. The exposure of core fucose residues and terminal sialic residues differed significantly in paired sera samples after freezing. Combined parameters of fucose and sialic acid exposure on native IgG glycans using frozen sera samples serve as a discriminative marker between MS and NHD. For AAL exposure, the discrimination of MS was characterized by AUROC of 0.906, sensitivity of 76.7% and specificity of 59.0% (P < 0.0001).
Interaction of 4 allotropic modifications of carbon nanoparticles with living tissues
S. Ya. Paryzhak1, T. I. Dumych1, S. M. Peshkova1,2,
E. E. Bila2, A. D. Lutsyk1, A. Barras3,
R. Boukherroub3, S. Szunerits3, R. O. Bilyy1
1Danylo Halytsky Lviv National Medical University, Ukraine;
2Ivan Franko Lviv National University, Ukraine;
3Univ. Lille, CNRS, Centrale Lille, ISEN, Univ. Valenciennes, France;
e-mail: r.bilyy@gmail.com
Received: 19 January 2019; Accepted: 20 March 2019
Environmental pollution and technological progress lead to carbon nanoparticles that pose a serious health risk. They are present in soot, dust, and printing toner and can also be formed during grinding and cutting. Human neutrophils are able to sequester foreign material by formation of neutrophil extracellular traps (NETs), a process that can cause a strong inflammatory response. In the current work we compared proinflammatory properties of different carbon-based nanostructures: nanodiamonds, graphene oxide, fullerenes C60 and carbon dots. We tested adjuvant properties of carbon nanoparticles in a murine immunization model by investigating humoral (specific IgG and IgM antibodies) and cellular (delayed type hypersensitivity) immune responses. The ability of NETs to sequester nanoparticles was analyzed in a mouse air pouch model and neutrophil activation was verified by in vivo tracking of near-infrared labeled nanodiamonds and ex vivo fluorescent assays using human blood-derived neutrophils. All carbon nanoparticles exhibited proinflammatory adjuvant-like properties by stimulating production of specific IgG but not IgM antibodies (humoral immune response). The adjuvant-like response decreased in this order: from nanodiamonds, graphene oxide, fullerenes C60 to carbon dots. None of the studied carbon nanoparticles triggered a delayed type hypersensitivity reaction (cellular immune response). Nanodiamonds and fullerenes C60 were sequestrated in the body by NETs, as confirmed in the air pouch model and by in vivo fluorescent tracking of near-infrared labeled nanodiamonds.
Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance
O. S. Dziuba1, V. O. Chernyshenko1, Ie. A. Hudz1, L. O. Kasatkina1, T. M. Chernyshenko1,
P. P. Klymenko2, H. V. Kosiakova1, T. M. Platonova1, N. M. Hula1, E. V. Lugovskoy1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: oksana.dziuba86@gmail.com;
2State Institute of Gerontology of AMS of Ukraine, Kyiv
Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (IR) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. Thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (HFD) in white rats. Blood samples were collected from 7 control and 14 obese IR rats. Prothrombin time (PT) and partial activated thromboplastin time (APTT) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activating enzymes from snake venoms. Platelet aggregation was measured and their count determined using Aggregometer Solar AP2110. The aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U Test. The haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. PT and APTT demonstrated that blood coagulation time strongly tended to decrease in obese IR rats in comparison to the control group. It was also detected that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese IR rats. A prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese IR rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesity-induced IR compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced IR which we assume indicate early development of atherosclerosis.
4-Thiazolidinone-based derivatives rescue TNAα-inhibited osteoblast differentiation in mouse mesenchymal precursor cells
Kh. V. Malysheva1,2,3, N. S. Finiuk1, O. K. Pavlenko4, D. Ya. Havrylyuk5,
R. B. Lesyk5, R. S. Stoika1, O. G. Korchynskyi1,3
1Institute of Cell Biology, NAS of Ukraine, Lviv;
2Insitute of Animal Biology, NAAS of Ukraine, Lviv;
3Centre for Innovative Research in Medical and Natural Sciences,
Rzeszow University and Medical Faculty, Poland;
4Ivan Franko National University of Lviv, Ukraine;
5Danylo Halytsky Lviv National Medical University, Ukraine;
e-mail: olexkor@hotmail.com
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of yet unknown etiology. Tumor necrosis factor α (TNFα) is recognized as a regulatory substance that plays a central role in RA development and progression. On the other side, the bone morphogenetic protein (BMP) and Wnt signaling pathways are key mechanisms that induce and support cartilage and bone formation and maintenance. Previous studies showed that the pro-inflammatory cytokines TNFα and interleukin 1β (IL-1β) are central players in the inhibition of activity of skeletogenesis. The aim of this study was to evaluate the anti-inflammatory activity of novel 4-thiazolidinone-based derivatives towards TNFα–induced pro-inflammatory effects during bone formation. We performed in vitro evaluation of functional effects of 4-thiazolidinones denoted as Les-4368, Les-4370, Les-3882 and Les-3288 that were used in different doses (0.02, 0.1, 0.3 and 1.0 μM) on the TNFα-mediated inhibition of the BMP-induced osteoblast differentiation in mouse mesenchymal precursor (stem) cells of C2C12 line. Treatment of these cells with TNFα completely inhibited their myogenic differentiation, as well as strongly inhibited the BMP-induced osteogenesis. Strikingly, the treatment of C2C12 cells with Les-4368 and Les-3882 rescued the osteoblast differentiation from negative control of TNFα, and, moreover, converted this cytokine from the inhibitor of osteogenesis into its stimulator. Western-blot analysis of Inhibitory κBα (I-κBα) degradation was used to elucidate a mechanism of the anti-inflammatory effects. Les-3882 was more active, and it stimulated osteoblast differentiation at low dose (0.1 μM), presumably, via modulation of the NF-κB signaling pathway.