Biophysical Bulletin

Ion homeostasis in the regulation of intracellular pH and volume of human erythrocytes

О. І. Dotsenko, G. V. Taradina (Author) — Wed, 07 Aug 2024 00:00:00 +0000

Background: Cell volume maintenance by regulating the water and ion content is crucial for the survival and functional fullness of human erythrocytes. However, cells are incredibly complex systems with numerous, often competing, reactions occurring simultaneously. Hence, anticipating the overall behavior of the system or acquiring a new understanding of how the subcomponents of the system interact might pose a considerable challenge in the absence of employing mathematical modeling methods.

Objectives: Creation of a mathematical metabolic model of erythrocyte ion homeostasis to study the mechanisms of erythrocyte volume stabilization and intracellular pH in in vitro experiments.

Material and Methods: The mathematical model was developed using general approaches to modeling cellular metabolism, which are based on systems of ordinary differential equations describing metabolic reactions, passive and active ion fluxes. The generation of the model and all computations, relying on the model, were executed utilizing the COPASI 4.38 simulation environment. Changes in intracellular pH, Na⁺/K⁺-ATPase, and Ca²⁺-ATPase activities of donor erythrocytes incubated in saline solutions in the absence and presence of Ca²⁺ ions were used to test the model.

Results: The kinetic model of erythrocyte ion homeostasis was created. Using realistic parameters of the system changes over time in cell volume, concentrations of metabolites, ions fluxes and transmembrane potential were calculated. The simulation results were used to analyze the reasons for changes in the resistance to acid hemolysis of erythrocytes under the conditions of their incubation in saline solutions of different compositions.

Conclusion: We show that cation homeostasis in erythrocytes is maintained mainly by the active movement of Na⁺ and K⁺ through Na⁺, K⁺-ATPase, combined with relatively lower passive permeability through other transport pathways. In the presence of Ca²⁺ ions and the activation of potassium release through Gardos channels, the cell volume is stabilized due to a change in the transmembrane potential and activation of electrodiffusion ion fluxes. The study demonstrated that the reduction in acid resistance of erythrocytes during incubation in a saline solution is associated with a decrease in their cell volume, whereas the increase in acid resistance during incubation in the presence of Ca²⁺ ions is linked to the activation of the Na⁺/H⁺ exchanger.

C60 fullerene improves the recovery of biomechanical parameters of muscle soleus contraction in rats after chronic alcoholization

Wed, 21 Aug 2024 00:00:00 +0000

Background: Recovery of biomechanical parameters of contraction of muscles damaged by alcoholic myopathy is a rather complex and long-term process. Therefore, the search for effective therapeutic means for its acceleration is an extremely urgent task in biomedicine.

Aim of work: The effect of C₆₀ fullerene aqueous solution (C₆₀FAS) on the dynamics of skeletal muscle contraction in rats after 9 months of chronic alcoholization and 2 months after cessation of alcohol consumption was investigated.

Materials and Methods: When analyzing the miotic response using tensometry, such biomechanical parameters as the time of reduction of the muscle force response by 50% from the initial value, the values of the contraction force and the impulse of the muscle force were evaluated.

Results: It has been shown that animals orally administered alcohol and C₆₀FAS (daily dose of 1 mg/kg) together (scheme II) during the experiment showed an increase in muscle force response by 40–45±2% compared with the group of alcoholized animals and by 12–15±1% compared with the group of rats administered C₆₀FAS 1 h after alcohol ingestion (scheme I). The positive effect of C₆₀FAS administration according to scheme II and scheme I was 34±2% and 10±1%, respectively, compared with the group of alcoholized animals in the case of recording the time of reduction of the muscle force response by 50% of the initial value. After 2 months of rehabilitation, the level of minimum muscle contraction force when using C₆₀FAS in both schemes differed by about 15±1% compared to the group of alcoholized animals, and the time of reduction of the force response by 50% was not significantly recorded. Finally, the use of C₆₀FAS revealed a significant increase in the magnitude of the muscle force impulse: up to 86±4% (scheme I) and almost to control values — 94±2% (scheme II).

Conclusions: The obtained results indicate the prospects of using C₆₀FAS to restore the biomechanical parameters of skeletal muscle contraction during long-term development of alcoholic myopathy.

Determining the relationship between the speed of motion of large permanent magnets and the trajectory of implants in magnetic stereotaxic systems

J. Hankun, O. G. Avrunin (Author) — Wed, 07 Aug 2024 13:36:28 +0000

Background: The magnetic stereotaxic system is a new type of neurosurgical intervention that is in the experimental stage. This method allows the implant to be controlled non-contact by an external magnetic field, allowing it to move along an arbitrary trajectory to a lesion located in a deep structure of the brain tissue to deliver hyperthermia to the lesion site or deliver medication through a catheter. In previous studies, we have found that it is completely feasible for the implant to move along the arc trajectory, so we need to determine the relationship between the movement speed of the large permanent magnet that constitutes the external magnetic field and the implant movement trajectory, so as to control the implant movement more precisely.

Objectives: Investigate the effect of the speed of motion of large permanent magnets, which constitute the external magnetic field, on the trajectory of implants (small permanent magnets).

Materials and Methods: Firstly, three sets of computer simulation experiments were conducted, each group of experiments only changed the operating speed of large permanent magnets, and the changes in the trajectories of small and medium-sized permanent magnets in the three sets of experiments were observed and compared. After that practical experiments are carried out to validate the results of the computer simulation experiments by means of the slide rail system controlled by an Arduino microcontroller.

Results: The relationship between the moving speed of the large permanent magnet and the trajectory of the small permanent magnet was determined by simulation experiments, and the changes in the strength of the surrounding magnetic field during the movement of the implant were calculated. Afterwards, it was verified by practical experiments. The faster the large permanent magnet moves, the shorter the distance that the small permanent magnet moves along the linear trajectory, and the longer the distance that moves along the arc trajectory; The slower the large permanent magnet moves, the longer the small permanent magnet travels along a straight trajectory and the shorter the distance it travels along an arc trajectory.

Conclusions: In this research, we have determined the relationship between the running speed of the large permanent magnet that constitutes the external magnetic field and the implant's moving trajectory by combining computer simulation experiments with practical experiments, i.e., the faster the large permanent magnet moves, the shorter the implant's moving distance is along a straight line trajectory, and the longer the moving distance is along a curved line trajectory. This means that we can control the distance and steering angle of the implant more accurately, which makes the study of the magnetic stereotaxic system further, and lays a theoretical foundation and provides a large amount of experimental data for the implant to be able to reach the diseased site located in the deep structure of the brain tissue along complex pathways in neurosurgical interventions with the participation of the magnetic stereotaxic system.

Segmented algorithm for three-dimensional reconstruction in linear scan geometry

T. G. Vikhtinskaya, K. E. Lapitan, K. E. Nemchenko (Author) — Thu, 08 Aug 2024 10:34:58 +0000

Background: Computer tomography is recognized as one of the most powerful methods for diagnosis, and monitoring of a wide range of diseases. It provides the ability to obtain detailed information about the internal structure of organs and bones. Despite the success of computed tomography in areas such as three-dimensional mammography or lung radiography, it has not achieved the same level of widespread as, for example, magnetic resonance imaging, even if CT offers greater accuracy. This is primarily due to safety limitations on the permissible number of examinations due to the harmfulness of X-ray radiation to the patient. One of the main challenges facing researchers is the need to reduce the time of the entire examination and decrease the radiation exposure to the patient. Overcoming these challenges is crucial for improving the overall efficiency of medical services, optimizing treatment plans, and ultimately enhancing patient outcomes. Thus, addressing these issues through innovative algorithms and methods in computed tomography holds significant potential for revolutionizing medical diagnostics and ensuring continuous progress in modern healthcare.

Objectives: The aim of this work was to develop an algorithm for three-dimensional reconstruction that is independent of the conicity of the radiation beam. Therefore, it allows for accurate reconstruction of the entire object with a single rotation of the radiation source around the investigated object.

Materials and Methods: The work utilizes methods of integral transforms and computer modeling to solve inverse problems arising in computer tomography.

Results: An analytical inversion formula was obtained for three-dimensional computer tomography with linear scan geometry and segmentation. The feasibility of the developed algorithm was verified, and a methodology for research with linear motion of the conical emitter and detectors was developed.

Conclusions: The developed algorithm improves the reconstruction of object layers significantly distant from the plane in which the emitter and detector move, compared to existing algorithms.

Identification of potential corticosteroid binding sites on the SARS CoV-2 main protease Mpro — in silico docking study

Mon, 12 Aug 2024 08:49:40 +0000

Background: Currently, an increase in the number of new cases of Covid-19 caused by the severe acute respiratory syndrome virus (SARS-CoV-2) is recorded in Ukraine and the world. SARS-CoV-2 provokes exacerbation of chronic diseases and activates inflammatory and allergic reactions. A severe course of Covid-19 increases the duration of hospitalization and the mortality rate among the population. Pathogenetic therapy is carried out with systemic corticosteroids, which suppress the cytokine storm by mitigating the SARS-CoV-2-induced systemic inflammatory response and inhibit SARS-CoV-2 main protease Mpro, a key component of viral replication.

Objectives: The aim of this study is to identify the potential corticosteroid binding sites on SARS CoV-2 main protease Mpro based on the analysis of the energetic and topological characteristics of the complexes as well as to investigate the inhibitory activity of selected corticosteroids against Mpro.

Material and Methods: The crystal structure of Mpro (ID: 6LU7 from Protein Data Bank) (www.rcsb.org) was chosen as a docking target. Molecular docking methods (AutoDock Tools 1.5.7, AutoDock Vina 1.1.2) were used to gain insight into the binding affinity Mpro with systemic corticosteroids such as dexamethasone (DEX), prednisone (PRED), prednisolone (PNL), methylprednisolone (Medrol), triamcinolone (TAC), and hydrocortisone (HCT). Visualization of docking results was done in PyMol 2.5. The protein-ligand interaction profiler (PLIP) and the LigPlot+ web tool were used to identify non-covalent interactions between Mpro and ligands (https://plip-tool.biotec.tu-dresden.de).

Results: In silico docking study demonstrated that all selected corticosteroids bound with amino acid residues of II and III domains of Mpro with binding energy in the range -7.8…-6.6 kcal/mol. The high binding affinity is found for dexamethasone-Mpro (-7.8 kcal/mol); for prednisone, prednisolone, methylprednisolone, triamcinolone, and hydrocortisone the binding energies were -7.4, -7.0, -7.5, -7.6 and -6.6 kcal/mol, respectively. It was shown that hydrogen bonds and hydrophobic interactions were involved in the formation of ligand-protein complexes mainly through residues such as Arg131, Lys137, Thr199, Asp289, Leu272, Leu286, Leu287, Tyr239, and Gly275, which formed the catalytic and distal sites for ligand binding. The inhibition constant of corticosteroids has ranged from 1.90 × 10^-6 to 14.4 × 10^-⁶ M.

Conclusion: Our results showed that the favorable binding sites for dexamethasone, prednisone, methylprednisolone, and triamcinolone are located in the catalytic site of domain II and the distal site of domain III of SARS-CoV-2 main protease Mpro with high binding affinities confirming the stability of the complexes. The low inhibition constants values for dexamethasone, prednisone, methylprednisolone, and triamcinolone further confirm the effectiveness of the selected corticosteroids as inhibitors of Mpro activity. Based on the binding energy as well as inhibition constants values dexamethasone, prednisone, methylprednisolone, and triamcinolone were identified as potential inhibitors for Mpro.

The 2nd Scientific workshop for students “Computational physics of DNA”

S. M. Perepelytsya, T. L. Bubon (Author) — Tue, 10 Sep 2024 13:00:13 +0000

The article is devoted to the 2nd Scientific workshop for students “Computational physics of DNA”.