Cardiovascular, rheumatic, kidney, and neurodegenerative diseases and mental disorders are a common cause of deterioration in the quality of life up to severe disability and death worldwide. Many pathological conditions, including this group of diseases, are based on increased cell death through apoptosis. It is known that this process is associated with signaling pathways controlled by a group of gaseous signaling molecules called gasotransmitters. They are unique messengers that can control the process of apoptosis at different stages of its implementation. However, their role in the regulation of apoptotic signaling in these pathological conditions is often controversial and not completely clear. This review analyzes the role of nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S), and sulfur dioxide (SO₂) in apoptotic cell death in cardiovascular, rheumatic, kidney, and neurodegenerative diseases. The signaling processes involved in apoptosis in schizophrenia, bipolar, depressive, and anxiety disorders are also considered. The role of gasotransmitters in apoptosis in these diseases is largely determined by cell specificity and concentration. NO has the greatest dualism; scales are more prone to apoptosis. At the same time, CO, H₂S, and SO₂ are more involved in cytoprotective processes.

—: Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.

Peripheral-nerve injury is a frequent cause of disability. Presently, no clinically effective neuroprotectors have been found. We have studied the NO-dependent expression of p53 in the neurons and glial cells of the dorsal root ganglia (DRG) of a rat’s spinal cord, as well as the role of NO in the death of these cells under the conditions of axonal stress, using sciatic-nerve axotomy as a model. It was found out that axotomy led to the nuclear–cytoplasmic redistribution of p53 in neurons, 24 h after trauma. The NO donor led to a considerable increase in the level of p53 in nuclei and, to a smaller degree, in the cytoplasm of neurons and karyoplasm of glial cells 4 and 24 h after axotomy. Application of a selective inhibitor of inducible NO-synthase (iNOS) provided the opposite effect. Introduction of the NO donor resulted in a significant increase in cell death in the injured ipsilateral DRG, 24 h and 7 days after trauma. The selective inhibitor of iNOS demonstrated a neuroprotective effect. Axotomy was shown to upregulate the iNOS in nuclei and cytoplasm of DRG cells. The NO-dependent expression of p53, which is particularly achieved through iNOS activation, is believed to be a putative signaling mechanism of neural and glial-cell death after axotomy.

Hydrogen sulfide (H₂S) donors are emerging as promising candidates for neuroprotective agents. However, H₂S-dependent neuroprotective mechanisms are not yet fully understood. We have demonstrated that an H₂S donor (sodium sulfide, Na₂S) reduces the expression of inducible NO synthase (iNOS) and amyloid-beta precursor protein (APP) in damaged neural tissue at 24 h and 7 days following traumatic brain injury (TBI). The application of aminooxyacetic acid (AOAA), an inhibitor of cystathionine β-synthase (CBS), produced the opposite effect. Seven days after TBI, iNOS expression was observed not only in the cytoplasm but also in some neuronal nuclei, while APP was exclusively localized in the cytoplasm and axons of damaged neurons. It was also shown that iNOS and APP were present in the cytoplasm of mechanoreceptor neurons (MRNs) in the crayfish, in axons, as well as in certain glial cells 8 h after axotomy. Na₂S and AOAA had opposing effects on axotomized MRNs and ganglia in the ventral nerve cord (VNC). Multiple sequence alignments revealed a high degree of identity among iNOS and APP amino acid residues in various vertebrate and invertebrate species. In the final stage of this study, biomodeling identified unique binding sites for H₂S, hydrosulfide anion (HS⁻), and thiosulfate (S₂O₃²⁻) with iNOS and APP.

Background: Cultured meat holds significant potential as a pivotal solution for producing safe, sustainable, and high-quality protein to meet the growing demands of the global population. However, scaling this technology requires innovative bioengineering approaches integrated with software methods to assess the growth of cell cultures. This study aims to develop a technology for 3D printing a hybrid meat product and subsequently design a finely tuned You Only Look Once (YOLO) model for detecting and counting lipoblasts, fibroblasts, and myogenic cells. Methods: Cultures of multipotent mesenchymal stem cells (MMSCs) and fibroblasts were obtained from the domestic rabbit Oryctolagus cuniculus domesticus. Standard protocols were employed to induce adipogenic and myogenic differentiation from MMSCs. Fibroblasts were isolated from skin biopsy samples. The 3D printing process utilized bioinks. The engineering approach involved the development of a unique print head integrated into a 3D printer. Confocal and transmission electron microscopy of the cells within the construct was performed. A dataset of digital images of lipoblasts, myogenic cells, and fibroblasts was created. Four models based on the YOLOv8-seg architecture were trained on annotated images, implemented in the Telegram bot. Results: Stable cultures of lipoblasts, myogenic cells, and fibroblasts were obtained. 3D-printed tissue constructs composed of rabbit cells, sodium alginate, and sunflower protein were successfully fabricated. A unique print head for a 3D printer was assembled. Confocal microscopy confirmed cell viability within the tissue construct. Ultrastructural analysis revealed dense intercellular contacts and high metabolic activity. The resulting product replicated the organoleptic and structural properties of natural meat. In the IT segment, the single-class model trained on lipoblasts achieved metrics of recall 85%, precision 77%, and mean Average Precision at IoU threshold 0.50 (mAP50) 79%, which improved in the multiclass model to recall 92%, precision 92%, and mAP50 81%. The IT solution was implemented in a Telegram bot capable of detecting and counting different cell types. Conclusions: A 3D tissue construct was achieved. Detailed microscopic analysis demonstrated cell viability and high metabolic activity within the polymerized alginate hydrogel. The engineered tissue product presents a potential alternative to natural meat. Additionally, the trained neural network models, implemented in a Telegram bot, proved effective in monitoring culture growth and identifying cell types in digital images across three cell cultures. As a result, we developed four YOLOv8 models and demonstrated that the multiclass model outperforms the single-class model. However, all models exhibited reduced accuracy in high-density cultures, where overlapping cells led to undercounting.

Traumatic brain injury (TBI) is one of the most common forms of neurotrauma, accompanied by significant disruptions in neuronal homeostasis and intercellular communication. A key protein involved in these processes is connexin 43 (Cx43), which facilitates the formation of gap junctions in the astrocytic network. In this study, using confocal and immunofluorescence microscopy, ultrastructural analysis, and molecular modeling, we investigated the dynamics of Cx43 expression and structural changes in neuroglia during various post-traumatic periods following TBI. It was shown that in the acute phase, 24 h post-injury, there is a reduction in Cx43 expression, accompanied by apoptotic neuronal degradation, disruption of nuclear NeuN localization, and destruction of cellular ultrastructure. By 7 days post-injury, a significant increase in Cx43 levels was observed, along with the formation of protein aggregates associated with pronounced reactive astrogliosis. Peripheral blood analysis revealed persistent neutrophilia, lymphopenia, and reduced monocyte levels, reflecting a systemic inflammatory response and immunosuppression, which was corroborated by a custom-trained neural network-based computer vision model. Linear regression and correlation analyses further identified a strong positive association between normalized monocyte levels and Cx43 expression, a moderate negative correlation with lymphocytes, and no significant correlation with neutrophils. Using a custom-built computer vision model, we confirmed these hematological trends and detected subtle changes, such as early increases in platelet counts, that were not captured by manual evaluation. The model demonstrated strong performance in classifying common blood cell types and proved to be a valuable tool for monitoring dynamic post-traumatic shifts in blood. Molecular dynamics modeling of Cx43 identified a pH-dependent mechanism of conformational reorganization under post-traumatic acidosis, mediated by the interaction between protonated His142 and Glu103. This mechanism mimics the structural consequences of the pathogenic E103K mutation and may play a critical role in the neurotoxic effects of Cx43 in TBI. These findings highlight the complexity of Cx43 regulation under traumatic conditions and its potential significance as a target for neuroprotective therapy.