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Authors = Tursonjan Tokay

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35 pages, 1208 KB  
Review
Epileptogenesis and Epilepsy Treatment: Advances in Mechanistic Understanding, Therapeutic Approaches, and Future Perspectives
by Akbota Mazhit, Burkitkan Akbay, Alexander Trofimov, Orynbassar Karapina, Serick Duysenbi and Tursonjan Tokay
Int. J. Mol. Sci. 2026, 27(3), 1175; https://doi.org/10.3390/ijms27031175 - 23 Jan 2026
Viewed by 1544
Abstract
Epilepsy remains an active and important area of research due to its complex etiology, significant global burden, and variable response to treatment. Current knowledge has provided valuable insights into the underlying molecular mechanisms of the disease and continues to guide the development of [...] Read more.
Epilepsy remains an active and important area of research due to its complex etiology, significant global burden, and variable response to treatment. Current knowledge has provided valuable insights into the underlying molecular mechanisms of the disease and continues to guide the development of novel therapeutic strategies. This review presents a comprehensive overview of the etiologies of epilepsy, as well as traditional and modern medical and surgical treatment approaches, while highlighting future research directions. Peer-reviewed articles retrieved from PubMed and Google Scholar were analyzed and synthesized to produce this review. The etiological complexity of epilepsy arises from genetic, metabolic, structural, and inflammatory mechanisms, which often coexist rather than act independently. A wide range of anti-seizure drugs (ASDs) is currently available, with many new agents targeting novel mechanisms under development. Surgical approaches, including resection, disconnection, corpus callosotomy, and neuromodulation, are widely used for patients with drug-resistant epilepsy and result in variable seizure outcomes. In addition, minimally invasive techniques such as laser interstitial thermal therapy (LITT), stereoelectroencephalography-guided radiofrequency thermocoagulation, gamma knife radiosurgery, and high-intensity focused ultrasound have gained clinical relevance and continue to be explored. Emerging technologies, including artificial intelligence, machine learning, and precision medicine, offer promising directions for future research. Although several potential biomarkers have been identified, none are yet established for routine clinical use. Continued investigation is essential to improve understanding of epileptogenesis and to develop safer, more effective therapies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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55 pages, 4973 KB  
Review
Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays
by Alexey Sarapultsev, Maria Komelkova, Oleg Lookin, Sergey Khatsko, Alexander Zhdanov, Stanislav Fedorov, Evgenii Gusev, Alexander Trofimov, Tursonjan Tokay and Desheng Hu
Biology 2025, 14(8), 939; https://doi.org/10.3390/biology14080939 - 25 Jul 2025
Cited by 2 | Viewed by 4346
Abstract
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript [...] Read more.
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system. Full article
(This article belongs to the Special Issue Social Behavior in Zebrafish)
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52 pages, 6090 KB  
Review
Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies
by Alexey Sarapultsev, Maria Komelkova, Oleg Lookin, Sergey Khatsko, Evgenii Gusev, Alexander Trofimov, Tursonjan Tokay and Desheng Hu
Pathophysiology 2024, 31(4), 709-760; https://doi.org/10.3390/pathophysiology31040051 - 6 Dec 2024
Cited by 14 | Viewed by 10528
Abstract
Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths [...] Read more.
Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths and limitations of commonly used rat models, such as single prolonged stress (SPS), stress–re-stress (S-R), and predator-based paradigms, in replicating human PTSD pathology. While these models provide valuable insights into neuroendocrine responses, genetic predispositions, and potential therapeutic targets, they face challenges in capturing the full complexity of PTSD, particularly in terms of ethological relevance and translational validity. We assess the degree to which these models mimic the neurobiological and behavioral aspects of human PTSD, highlighting areas where they succeed and where they fall short. This review also discusses future directions in refining these models to improve their utility for translational research, aiming to bridge the gap between preclinical findings and clinical applications. Full article
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13 pages, 2520 KB  
Review
Double-Edge Effects of Leucine on Cancer Cells
by Burkitkan Akbay, Zhannur Omarova, Alexander Trofimov, Bayan Sailike, Orynbassar Karapina, Ferdinand Molnár and Tursonjan Tokay
Biomolecules 2024, 14(11), 1401; https://doi.org/10.3390/biom14111401 - 4 Nov 2024
Cited by 11 | Viewed by 6187
Abstract
Leucine is an essential amino acid that cannot be produced endogenously in the human body and therefore needs to be obtained from dietary sources. Leucine plays a pivotal role in stimulating muscle protein synthesis, along with isoleucine and valine, as the group of [...] Read more.
Leucine is an essential amino acid that cannot be produced endogenously in the human body and therefore needs to be obtained from dietary sources. Leucine plays a pivotal role in stimulating muscle protein synthesis, along with isoleucine and valine, as the group of branched-chain amino acids, making them one of the most popular dietary supplements for athletes and gym-goers. The individual effects of leucine, however, have not been fully clarified, as most of the studies so far have focused on the grouped effects of branched-chain amino acids. In recent years, leucine and its metabolites have been shown to stimulate muscle protein synthesis mainly via the mammalian target of the rapamycin complex 1 signaling pathway, thereby improving muscle atrophy in cancer cachexia. Interestingly, cancer research suggests that leucine may have either anti-cancer or pro-tumorigenic effects. In the current manuscript, we aim to review leucine’s roles in muscle protein synthesis, tumor suppression, and tumor progression, specifically summarizing the molecular mechanisms of leucine’s action. The role of leucine is controversial in hepatocellular carcinoma, whereas its pro-tumorigenic effects have been demonstrated in breast and pancreatic cancers. In summary, leucine being used as nutritional supplement for athletes needs more attention, as its pro-oncogenic effects may have been identified by recent studies. Anti-cancer or pro-tumorigenic effects of leucine in various cancers should be further investigated to achieve clear conclusions. Full article
(This article belongs to the Section Molecular Biology)
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14 pages, 2360 KB  
Article
Evaluation of Biochemical Serum Markers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Obese Women in Kazakhstan: Is Anti-Müllerian Hormone a Potential Marker?
by Malika Madikyzy, Aigul Durmanova, Alexander Trofimov, Burkitkan Akbay and Tursonjan Tokay
Biomedicines 2024, 12(10), 2333; https://doi.org/10.3390/biomedicines12102333 - 14 Oct 2024
Cited by 4 | Viewed by 3059
Abstract
Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age. In Kazakhstan, the prevalence of this syndrome is particularly high compared with other countries and the global average. Currently, the diagnosis of PCOS is based [...] Read more.
Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age. In Kazakhstan, the prevalence of this syndrome is particularly high compared with other countries and the global average. Currently, the diagnosis of PCOS is based on internationally established Rotterdam criteria, using hyperandrogenism as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible misdiagnosis, an additional criterion, especially for the diagnosis of PCOS in obese women, could be considered. The aim of this study was to identify whether anti-Müllerian hormone (AMH) or other biochemical criteria can be used for this purpose. Methods: A total of 138 women were recruited for this study and grouped into control (n = 46), obese subjects without PCOS (n = 67), and obese patients with PCOS (n = 25). The health status, anthropometric parameters, and serum indicators for glucose, glycosylated hemoglobin, and hormone levels were examined for all subjects. Statistical data were analyzed using GraphPad Prism 10 software for interpretation of the data. Results: Serum AMH, testosterone, and LH were positively correlated in obese PCOS patients, while AMH and FSH were negatively correlated. Compared with other biochemical indicators, the serum AMH and testosterone levels in obese PCOS patients were significantly higher than those in non-PCOS patients (regardless of obesity), and AMH was also positively correlated with testosterone. Conclusions: AMH appears to be a reliable criterion in addition to testosterone for the diagnosis of PCOS in obese women. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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21 pages, 17481 KB  
Review
Vitamin D in Central Nervous System: Implications for Neurological Disorders
by Bayan Sailike, Zhadyra Onzhanova, Burkitkan Akbay, Tursonjan Tokay and Ferdinand Molnár
Int. J. Mol. Sci. 2024, 25(14), 7809; https://doi.org/10.3390/ijms25147809 - 17 Jul 2024
Cited by 39 | Viewed by 13435
Abstract
Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and [...] Read more.
Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain. Full article
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16 pages, 2725 KB  
Article
Plant Extract of Limonium gmelinii Attenuates Oxidative Responses in Neurons, Astrocytes, and Cerebral Endothelial Cells In Vitro and Improves Motor Functions of Rats after Middle Cerebral Artery Occlusion
by Tulendy Nurkenov, Andrey Tsoy, Farkhad Olzhayev, Elvira Abzhanova, Anel Turgambayeva, Aizhan Zhussupova, Bharathi Avula, Samir Ross, Aigerim Aituarova, Dariya Kassymova, Galiya Zhusupova, Tamara Shalakhmetova, Tursonjan Tokay, James C. Lee and Sholpan Askarova
Antioxidants 2021, 10(11), 1814; https://doi.org/10.3390/antiox10111814 - 15 Nov 2021
Cited by 7 | Viewed by 3401
Abstract
There are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich [...] Read more.
There are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2, and TNF-α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P-selectin expression, and activity of ERK1/2 were evaluated by quantitative immunofluorescence analysis, confocal microscopy, and MAPK assay. In vivo, sensorimotor functions in rats with middle cerebral artery occlusion (MCAO) were assessed. In neurons NMDA induced overproduction of ROS, in astrocytes TNF-α initiated ROS generation, NADPH oxidase activation, and phosphorylation of ERK1/2. In CECs, the exposure by TNF-α induced oxidative stress and triggered the accumulation of P-selectin on the surface of the cells. In turn, pre-treatment of the cells with the extract of L. gmelinii suppressed oxidative stress in all cell types and pro-inflammatory responses in astrocytes and CECs. In vivo, the treatment with L. gmelinii extract improved motor activity in rats with MCAO. Full article
(This article belongs to the Special Issue Antioxidants in Neurons)
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16 pages, 4022 KB  
Article
Mesenchymal Stem Cells Coated with Synthetic Bone-Targeting Polymers Enhance Osteoporotic Bone Fracture Regeneration
by Yuliya Safarova (Yantsen), Farkhad Olzhayev, Bauyrzhan Umbayev, Andrey Tsoy, Gonzalo Hortelano, Tursonjan Tokay, Hironobu Murata, Alan Russell and Sholpan Askarova
Bioengineering 2020, 7(4), 125; https://doi.org/10.3390/bioengineering7040125 - 12 Oct 2020
Cited by 5 | Viewed by 4908
Abstract
Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor [...] Read more.
Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration. Full article
(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering)
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16 pages, 886 KB  
Review
Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine
by Bolat Sultankulov, Dmitriy Berillo, Karina Sultankulova, Tursonjan Tokay and Arman Saparov
Biomolecules 2019, 9(9), 470; https://doi.org/10.3390/biom9090470 - 10 Sep 2019
Cited by 294 | Viewed by 12226
Abstract
Over the last few decades, chitosan has become a good candidate for tissue engineering applications. Derived from chitin, chitosan is a unique natural polysaccharide with outstanding properties in line with excellent biodegradability, biocompatibility, and antimicrobial activity. Due to the presence of free amine [...] Read more.
Over the last few decades, chitosan has become a good candidate for tissue engineering applications. Derived from chitin, chitosan is a unique natural polysaccharide with outstanding properties in line with excellent biodegradability, biocompatibility, and antimicrobial activity. Due to the presence of free amine groups in its backbone chain, chitosan could be further chemically modified to possess additional functional properties useful for the development of different biomaterials in regenerative medicine. In the current review, we will highlight the progress made in the development of chitosan-containing bioscaffolds, such as gels, sponges, films, and fibers, and their possible applications in tissue repair and regeneration, as well as the use of chitosan as a component for drug delivery applications. Full article
(This article belongs to the Special Issue New Targets and Strategies in Regenerative Medicine)
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