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Proteins of plasminogen/plasmin system: multifaceted roles in health and disease

A. O. Tykhomyrov*, O. I. Yusova, L. G. Kapustianenko, I. I. Patalakh,
T. A. Yatsenko, V. L. Bilous, T. V. Grynenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Enzyme Chemistry and Biochemistry, Kyiv;
*e-mail: artem_tykhomyrov@ukr.net

Received: 20 April 2025; Revised: 02 June 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

The plasminogen/plasmin (Pg/Pm) system is a cornerstone of various biological processes, encompassing roles in fibrinolysis, angiogenesis, inflammation, wound healing, and tumor biology. This review consolidates knowledge on the multifaceted functions of the Pg/Pm system proteins in health and disease, highlighting historical developments, recent advancements, and the contributions of the Department of Enzyme Chemistry and Biochemistry to the understanding of their molecular mechanisms of function. We have explored the regulation of fibrinolysis and its intricate interplay with proteins of the Pg/Pm system, delving into their pivotal role in hemostatic balance. Reciprocal interactions between Pg/Pm system proteins and platelets underscore their contribution to thrombosis, fibrinolysis, inflammation, and vascular remodeling. In oncology, Pg/Pm system proteins orchestrate tumor growth and metastasis through their involvement in extracellular matrix remodeling, angiogenesis, and cancer cell survival. However, angiostatins – proteolyti­cally-derived fragments of Pg/Pm – emerge as multifunctional polypeptides, which are known to affect cell migration, angiogenesis, and inflammation, suppress tumor growth and metastasis. Contribution of Pg/Pm to reparative processes, including wound healing, further emphasizes their therapeutic potential in regenerative medicine. Moreover, these proteins play crucial roles in ocular health, where their dysregulation may lead to the pathogenesis of ophthalmic diseases. In conclusion, advancement of our understanding of this versatile system functions through continued research is pivotal for applications of these proteins as diagnostic and prognostic biomarkers for cardiovascular disorders, inflammatory pathologies, cancer, autoimmune conditions, and various diabetic complications, offering insights into early detection of disease and development of innovative therapeutic strategies, ultimately driving progress in personalized medicine.

Department of Cell Signaling relay race of time: from studying the structure and function of individual proteins to analyzing protein–protein interaction networks

O. O. Hudkova, L. B. Drobot*

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Cell Signaling, Kyiv;
*e-mail: drobot@biochem.kiev.ua

Received: 30 September 2025; Revised: 08 October 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

The review presents the history of establishment, key achievements, and development prospects of the Department of Cell Signaling at the Palladin Institute of Biochemistry of the NAS of Ukraine. As a structural unit of the institution, the Department was established in 2018 through the merger of two separate subdivisions: one of the oldest, the Department of Metabolic Regulation (founded in 1944), and the youngest, the Laboratory of Cell Signaling (founded in 2006). From its inception, the department’s primary research focus has been the study of the structure and functions of individual animal and microbial proteins. Significant contributions to the fundamental and applied achievements during that period were made by leaders of the Department, Dr.Sci., Professor Szörényi E.T., and Academician of NASU Huliy M.F., which were recognized with State Prizes of the USSR and the Ukrainian SSR (1953, 1978, 1988). Considerable attention has been given­ to transforming the department’s research direction to meet modern standards in molecular cell biology, a shift logically linked to the work of the unified unit under the leadership of Dr.Sci., Professor L.B. Drobot. This transformation involved not only the formal merger of two teams but also the integration of their scientific accomplishments and intellectual potential, combining traditional and innovative research approaches. The scientific paths of both subdivisions inevitably converged, necessitating joint investigations in response to contemporary challenges and societal demands. The department’s central focus became the elucidation of signaling mechanisms involved in the coordinated regulation of proliferation, differentiation, and apoptosis in normal and transformed cells with the participation of adaptor/scaffold protein Ruk/CIN85. Through the efforts of the department’s researchers, the pivotal role of Ruk/CIN85 in controlling the plasticity of tumor cells of various origins was convincingly demonstrated–particularly in the development of cancer stem cell traits, chemoresistance, tumor progression, and/or differentiation.

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.

Protein mysterious structure and numerous functions department

V. O. Chernyshenko*, V. I. Gryshchuk

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Protein Structure and Function, Kyiv;
*e-mail: bio.cherv@gmail.com

Received: 02 July 2025; Revised: 30 July 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

This overview is dedicated to the history of the Department of Protein Structure and Function at the Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine. It outlines the department’s main scientific objectives and highlights its key achievements. In particular, it describes research related to patient blood management, fundamental studies of fibrinogen structure and function, the development of next-generation antithrombotic prototypes, as well as the creation and clinical testing of diagnostic assays. Special attention is given to inventions and studies aimed at addressing pressing social issues, including post-traumatic stress disorder and the consequences of COVID-19. The importance of maintaining continuity in hemostasis research is emphasized, as it enables the generation of unique scientific results and their implementation in medical practice.

Department of Muscle Biochemistry: calixarenes as modulators of energy-dependent Са(2+)-transporting pumps in smooth muscles

S. O. Kosterin

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine,
Department of Muscle Biochemistry, Kyiv;
e-mail: kinet@biochem.kiev.ua

Received: 12 May 2025; Revised: 18 June 2025;
Accepted: 30 October 2025; Available on-line: 02 December 2025

In this scientific-historical review devoted to the recent achievements of the Muscle Biochemistry Department of the Palladin Institute of Biochemistry, the NAS of Ukraine, we synthesize findings from interdisciplinary investigations of intracellular calcium homeostasis in smooth muscle (exemplified by the myometrium) conducted at the interface of biochemistry, physical and organic chemistry, biophysics, and mathematical/computational modeling. We emphasize that the selected calix[4]arenes considered here act selectively as inhibitors of the Mg2+,ATP-dependent calcium and sodium pumps – ion-transporting ATPases (electroenzymes Ca2+,Mg2+-ATPase and Na+,K+-ATPase) – of the plasma membrane of smooth-muscle cells, enabling controlled modulation of intracellular Ca2+ homeostasis and the contractile activity of the myometrium. The data obtained also indicate that the selected calix[4]arenes can be regarded as compounds suitable for efficient investigation of mitochondrial function in smooth-muscle cells, in particular the mechanisms of transmembrane Ca2+ exchange, the principles governing membrane-potential formation, and the contribution of these subcellular structures to the control of the mechanokinetics of the contraction–relaxation cycle. It is shown that some calix[4]arenes act as effectors of the ATPase activity of contractile proteins and protect this activity from the inhibitory influence of heavy-metal ions. Taken together, these results outline biochemical approaches to the fine regulation of calcium fluxes and smooth-muscle contractility and underscore the potential of calix[4]arenes as selective “molecular platforms” useful for addressing fundamental and applied (biomedical) problems in contemporary physico-chemical muscle biology.

Department of Molecular Immunology. History and scientific achievements

S. V. Komisarenko

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

The Department of Molecular Immunology was established in September 1975. Since its founding, the Department has focused on two main areas of research: 1) investigating the mechanisms underlying the biological, in particular immunotropic and antitumor, effects of organophosphorus derivatives of inorganic pyrophosphate, and 2) developing and applying methods of immunochemical analysis of proteins to determine the molecular mechanisms of antigen recognition by the immune system. Over the years, the Department has developed a number of antitumor immunotoxins, studied intracellular signaling mechanisms in lymphocytes, revealed an adverse effect of low-dose radiation on the “natural” immune system in Chernobyl accident liquidators, and explored the immunochemical structures of the neurotoxin apamin, cytochrome c, fibrinogen, and fibrin molecules. Since 2020, the research of the Department has focused on various aspects of ensuring national security and defense, particularly in response to the large-scale COVID-19 pandemic caused by the SARS-CoV-2 coronavirus, and on developing potential therapeutic agents for the complex treatment of PTSD and injuries, which are crucial during large-scale warfare.

Biochemistry is the language of life. A century of research and discovery (Preface)

Serhiy Komisarenko

Director of the Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: svk@biochem.kiev.ua

A hundred years is not merely a span of time – it is a distance measured by generations of scientists and by the depth of knowledge gained in the constant pursuit of truth. During this period, the world has undergone fundamental transformations – from the first radio broadcasts and the discovery of the DNA structure to artificial intelligence and genome decoding. These changes have inevitably influenced the development of science, particularly biochemistry – a field that today combines molecular precision, interdisciplinarity, and the drive to apply knowledge for the preservation of life.

The century-long history of the Palladin Institute of Biochemistry is the story of how the Ukrainian school of biochemistry has been developed – a school that has harmoniously combined fundamental research with the solution of applied biomedical problems. From the first steps in the study of vitamins, enzymes, lipids, and proteins – to modern investigations of cellular signaling, immunomodulation, neurochemistry, molecular oncology, and biomedical innovations – the Institute’s path reflects the evolution of science itself.

This jubilee issue of the Ukrainian Biochemical Journal presents review articles from all ten departments of the Institute – each not only summarizes their scientific achievements but also outlines the horizons of the future.

The Department of Neurochemistry, tracing its roots back to 1925, has developed the understanding of the chemical topography of the nervous system, the mechanisms of neurotransmission, and the molecular basis of the action of neuroactive compounds – from classical studies to modern experiments in space biology.

The research of the Department of Molecular Immunology demonstrates how fundamental scien­ce, studying the regulation of the immune system, responds to the challenges of our time – the COVID-19­ pandemic and the consequences of war – by developing new approaches to treating post-traumatic stress disorders, dangerous bleeding and promoting wound healing.

The Department of Muscle Biochemistry explores the molecular mechanisms regulating ion transport and the role of calixarenes in the controlled modulation of smooth muscle contractility, combining­ biochemical insight with mathematical modeling.

Continuing a tradition of studying hemostasis, the Department of Protein Structure and Function develops innovative diagnostic tests and prototypes of next-generation antithrombotic agents.

The Department of Protein Structure and Function continues the tradition of studying hemostasis by developing diagnostic tests against the risk of thrombosis and prototypes of a new generation of antithrombotic agents.

The research conducted by the Department of Chemistry and Biochemistry of Enzymes focuses on uncovering the multifaceted functions of plasminogen/plasmin proteins in homeostasis, inflammation, oncogenesis, regeneration, and vascular biology, providing a basis for the development of personalized medical approaches.

The Department of Cellular Signaling Mechanisms shows how a shift in scale – from individual proteins to the network organization of signaling systems – opens new approaches to understanding oncogenesis and cellular plasticity.

A significant contribution to the development of molecular vitaminology has been made by the Department of Vitamin and Coenzyme Biochemistry, where researchers investigate the neurotropic action of vitamins B1, B3, and D3 and their derivatives, which hold potential for preventing neurodegenerative disorders.

The history of the Department of Lipid Biochemistry represents a path from the early hypothe­ses to the discovery of a new class of compounds, N-acylethanolamines that play a vital role in regulating physiological and pathological processes and open the way for the development of new therapeutic agents for a wide range of diseases.

At the Department of Molecular Biology, researchers explore the molecular mechanisms of glio­ma growth and the role of hypoxia and endoplasmic reticulum stress in regulating gene expression, offering valuable insights into the pathogenesis of the most aggressive brain tumors.

Finally, the Department of Scientific Information and Innovative Research provides a systematic analysis of the achievements of Nobel laureates, showing how great discoveries shape the course of modern life sciences.

Each of these reviews is not merely a scientific summary; it is a testament to living traditions, continuity of generations, and the tireless pursuit of knowledge. Today, as a century ago, biochemistry remains the science of life in its deepest sense. It reveals the mechanisms that sustain health, resilience, and adaptation, helping humanity to understand itself and the world in which it lives. Biochemistry is a science to which all generations of researchers at the Institute of Biochemistry in Kyiv have devoted their lives – where one of the main priorities has always been the constant rejuvenation of scientific community and the training of young scientists.

Ahead lie new challenges, new technologies, and, without doubt, new discoveries. Yet one thing remains unchanged – our faith in the power of scien­tific thought and in our calling to serve life. It is this spirit that unites the past, present, and future of the ever-young century-old Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine.

On the 75th Birthday of Academician of the NAS of Ukraine, Professor S. O. Kosterin

Contents UBJ, 2025, Volume 97, Issue 4

The unsung hero of science: Barbara McClintock, who won the Nobel Prize in Physiology or Medicine in 1983 for her discovery of mobile genetic elements

O. P. Matyshevska*, M. V. Grigorieva, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: matysh@yahoo.com

Received: 17 July 2025; Revised: 25 August 2025;
Accepted: 12 September 2025; Available on-line: 18 September 2025

In 1983, American plant biologist and cytogeneticist McClintock, one of the great loners of modern­ scien­ce, received the first woman scientist’s unshared Nobel Prize in Physiology or Medicine. Barbara McClintock’s research, conducted in the 1930s, long before the structure of DNA was deciphered, included creating­ the first genetic map of ten chromosomes composing the haploid set of maize microspores and cytological determination of gene location within individual chromosomes. Two phenomena with which Barbara McClintock’s name will forever be associated are crossing over and transposons. Her finding that chromosomes might exchange physical parts as part of gene exchange confirmed Morgan’s theory of inheritance. Experiments in 1940-1950s with the phenotypes of hybrid maize kernels led her to the concept that genetic elements, which she referred to as Dissociation and Activator controling elements, could transpose and regulate the genes by inhibiting or modulating their action. Her revolutionary findings were ahead of their time, in conflict with the established concept of a stable genome and met with scepticism and opposition. Much later, the scientific world accepted her ideas on mobile genetic elements, and it was recognition she appreciated but never sought. McClintock considered the genome as a highly sensitive organ that responds to unexpected events, often by genome restructuring, which scientists today are trying to understand. In this review, the scien­tific path and achievements of Barbara McClintock are analyzed.