Patologicheskaya Fiziologiya i Eksperimental'naya Terapiya (Pathological physiology and experimental therapy)

Re The effect of photodynamic therapy and surgical treatment of experimental breast cancer on the relationship of microRNAs (-21, -27a, -221, -429) of thymic mRNA with the thymus structure

Tue, 30 Sep 2025 00:00:00 +0300

Aim. To identify the effect of photodynamic therapy (PDT) and its combination with surgical treatment of breast cancer on the relationship of thymic microRNA (‑21, ‑27a, ‑221, ‑429) with the thymus structure in female Wistar rats.

Methods. The study was conducted on 80 anesthetized mature female Wistar rats. The relationship between the thymus structure and the amount of microRNA in the thymus was assessed after PDT for breast cancer (intramammary administration of N-methyl-N-nitrosourea) and after PDT and surgical treatment for breast cancer.

Results. After PDT, relationships were found only between pro-oncogenic microRNAs (‑21, ‑27a, ‑221) and cells in the corticomedullary zone and the central part of the medulla compared with the intact group and with breast cancer without treatment. Morphological changes in the thymus indicated the effect of PDT on the processes of both positive and negative selection. The relationships between thymic microRNAs and morphological changes in the thymus may indicate the effect of PDT on the attenuation of proliferative activity, differentiation and migration of T lymphocytes from the thymus compared to untreated breast cancer. PDT and subsequent surgical treatment of breast tumor, as compared to the PTD therapy, induced a significant increase in thymic microRNAs (‑21, ‑27a, ‑429). The following relationships were found: in the subcapsular zone, immunoblasts with microRNA‑21 and small lymphocytes with microRNA‑429; in the corticomedullary zone, small lymphocytes with microRNA‑27a; in the central part of the medulla, immunoblasts with microRNA‑21. Compared with PDT, the number of immunoblasts and medium lymphocytes decreased in the subcapsular zone and the central part of the cortical substance. The number of small lymphocytes increased in the central part of the cortical substance, and the number of small lymphocytes decreased in the central medulla and the corticomedullary zone. The number of epithelial reticular cells in the central part of the cortical substance and medullary substance was reduced.

Conclusion. This study revealed relationships of cells in thymus structural components with quantitative changes in thymic microRNA after PDT and surgical removal of the tumor, in comparison with PDT alone and along with morphological data. These relationships may be due to a decrease in the thymus proliferative activity, the activity of the processes of both positive and negative selection of T cells, as well as decreased activity of the processes of differentiation and migration of T lymphocytes from the thymus.

Erythrosomes - preparation and uptake by endothelium In Vitro

Tue, 30 Sep 2025 00:00:00 +0300

Annotation

Introduction. Many human diseases are pathogenetically associated with endothelial dysfunction, which motivates the development of drugs that affect endotheliocytes. To solve the problem of developing therapy aimed at the endothelium, it is proposed to use nanomedicine methods, namely, the creation of nanoscale structures that deliver a drug to endotheliocytes. Nanovesicles from human erythrocyte membranes are a promising candidate for the role of a non-toxic, biocompatible drug carrier in endotheliocytes. The aim of the work is to develop a technology for obtaining nanoscale vesicles of human erythrocyte membranes loaded with a model compound, and to study the absorption of the obtained vesicles by the endothelium in an In Vitro model.

The methodology. Erythrocyte ghosts were obtained by hypotonic hemolysis, loaded with a membrane impermeable fluorescing dye, the isotonicity of the medium was restored, and nanoscale erythrocyte vesicles were obtained by ultrasonic homogenization, which were then washed by dialysis or ultracentrifugation. Erythrosomes were characterized by photon correlation spectroscopy and transmission electron microscopy with reverse contrast. Cellular uptake of the erythrosomes by EA.Hy926 cells was studied using the flow cytofluorometry method and the cytotoxicity of erythrosomes was evaluated in an MTT test.

Results. Preparations of erythrosomes, nanoscale vesicles from erythrocyte ghosts, were obtained and characterized. It has been shown that erythrosomes loaded with membrane impermeable fluorescing dye are absorbed by cells of the human EA.Hy926 endothelial line, considered as an In Vitro model of the endothelium. The transport of erythrosomes into endotheliocytes is energy-dependent, as it is blocked at 4 ° C. Erythrosomes have no cytotoxic effect.

Conclusion. A simple and technologically advanced technique has been developed for obtaining nanoscale vesicles loaded with a model compound and absorbed by endotheliocytes from human erythrocyte membranes, which makes it possible to consider the obtained erythrosomes as promising means of drug delivery to the endothelium.

Changes in the subpopulation composition of tumor-infiltrating cytotoxic Т-lymphocytes and the expression of co-inhibitory molecules on their surface in stage III colorectal cancer

Victoria Viktorovna Kryukova, Victor Lvovich Tsepelev, Pavel Petrovich Tereshkov — Tue, 30 Sep 2025 00:00:00 +0300

Relevance: Studying the subpopulation composition of cytotoxic T-lymphocytes and the expression of co-inhibitory proteins on their surface in the tumor microenvironment is necessary for the development of new methods of targeted therapy for colorectal cancer (CRC).

Aim: To study the subpopulation composition of cytotoxic T-lymphocytes and the expression of co-inhibitory molecules on their surface in the primary tumor growth site in patients with stage III colon cancer.

Methods. The relative content of cytotoxic T-lymphocytes in the tumor microenvironment, the subpopulation composition of cytotoxic T-lymphocytes, as well as the expression of immune checkpoints (CTLA-4, PD-1, TIM-3) by CD8-positive cells were measured in 105 patients with stage III CRC by flow cytometry. The control group consisted of 75 patients who underwent colon surgery for non-neoplastic diseases.

Results. In patients with stage III CRC, the proportion of naive cells (CD3+CD8+CD45RA+CCR7+) in the primary tumor growth site was decreased by 23.1%; the relative content of cytotoxic T-lymphocytes of central memory (CD3+CD8+CD45RA-CCR7+) and effector memory (CD3+CD8+CD45RA-ССR7-) was increased by 1.5 and 1.4 times, respectively; and the number of terminally differentiated T-cells (CD3+CD8+CD45RA+ССR7-) was decreased. In CRC patients, on the surface of CD3+CD8+ lymphocytes in the tumor microenvironment, the expression of CD57 was increased by 1.9 times, the co-inhibitory CTLA-4 molecule by 1.9 times, and the TIM-3 protein by 2.5 times.

Conclusion. In patients with stage III CRC, the subpopulation composition of tumor-infiltrating cytotoxic T lymphocytes changes, which is evident as a decreased proportion of naive and terminally differentiated T cells along with an increase in the percentage of central and effector memory cells. In stage III CRC, the expression of co-inhibitory molecules (CTLA-4 and TIM-3) on cytotoxic T lymphocytes of the tumor microenvironment increases.

Cysteine, homocysteine and their redox status as a predictor of death in patients on hemodialysis

Tue, 30 Sep 2025 00:00:00 +0300

Introduction. Chronic kidney disease (CKD), especially its end stage, that requires renal replacement therapy, is characterized by high cardiovascular morbidity and mortality. Uremic syndrome associated with CKD facilitates oxidative stress, endothelial dysfunction, and inflammation and, thereby, plays a key role in the development of cardiovascular complications. Cysteine and homocysteine form a thiol-disulfide system in a state of dynamic equilibrium. The imbalance between reduced and oxidized forms of these aminothiols may reflect the degree of oxidative stress and its contribution to the development of CKD complications. The aim of this study was to identify the prognostic role of cysteine, homocysteine and their redox status in blood plasma of patients with terminal renal insufficiency.

Methods. The study included 47 patients who received renal replacement therapy (hemodialysis) for at least 3 months prior to blood sampling. The follow-up period was 3 years.

Results. It was found that a high level of total content of cysteine and homocysteine, a low level of their reduced forms, and a low redox status of cysteine (<1%) and homocysteine (<6%) are independent predictors of death in hemodialysis patients (odds ratio 4.7 and 4.8, respectively, p< 0.05). An increase in the plasma pool of homocysteine due to its insufficient utilization by the kidneys leads to an increase in its cellular concentration and activation of trans-sulfurization enzymes that convert homocysteine into cysteine. This contributes to an elevation of plasma cysteine. Disorders of homocysteine metabolism are not only evident as increased total cysteine content but also affect the thiol-disulfide balance of aminothiols.

Conclusion. The total content, reduced forms, and redox status of cysteine and homocysteine are independent predictors of death in hemodialysis patients. Assessment of the redox status can be useful for risk stratification and the development of personalized therapeutic strategies for restricting oxidative stress and improving prognosis in this category of patients. Further studies are needed to evaluate the effectiveness of antioxidant therapy and other interventions aimed at the correction of the redox balance in hemodialysis patients.

Morphological and morphometric characteristics of the liver in exposed to ferrihydrite nanoparticles

Tue, 30 Sep 2025 00:00:00 +0300

Introduction. Ferrihydrite nanoparticles (FNPs) are promising for various biomedical applications. However, the use of FNPs is associated with biosafety issues. The liver is one of the critically important organs exposed to nanomaterials. It plays a central role in metabolism and detoxification, and its damage can lead to serious adverse consequences. Therefore, studying effects of FNPs on the liver is a relevant and important task. The aim of the study was to evaluate the effect of FNPs on the liver morphological structure after oral administration, depending on the method of FNP synthesis.

Methods. The experiment was performed on 3 groups of laboratory mice (males, n=55): group 1 (n=15), control that was fed food not supplemented with FNPs; group 2 (n=20), experimental group, was fed food supplemented with synthetic FNPs; group 3 (n=20), experimental group, was fed food supplemented with biogenic FNPs. The feed mixture for the experimental groups was prepared in a laboratory mixer SL-12pnd. Biological material was sampled on days 1, 22, and 36 of the experiment. Liver samples were prepared according to standard histological methods and stained with hematoxylin-eosin, and with Perls Prussian blue to detect iron nanoparticles. The morphometric analysis of liver tissue was performed using the ViodeoTesT-Morphology 7.0 software. The significance of cross-sample differences (p) was assessed using the Mann−Whitney U-test. The significance of differences between dependent samples was assessed using the Wilcoxon T-test. Differences were considered statistically significant at p<0.05.

Results. The administration of FNPs with food leads to statistically significant changes in the morphometric parameters of the liver. In experimental groups 2 and 3, the diameter of the interlobular veins was significantly increased, which was associated with a decrease in the central vein diameter. The proportion of non-nuclear hepatocytes was markedly increased in both groups. Also, the liver tissue showed inflammation signs with varying intensity of pathological processes resulting in the impairment of the liver compensatory capabilities.

Conclusion. The study showed a negative effect of FNPs (both synthetic and biogenic) on the liver manifested in the form of necrobiotic changes in the liver parenchyma.

Analysis of the dependence of myocardial mitochondria endogenous respiration on physical characteristics of vibration

Tue, 30 Sep 2025 00:00:00 +0300

Introduction. The article addresses the problem of qualitative and quantitative assessment of the electron transport chain (ETC) bioenergetics of myocardial mitochondria in experimental animals exposed to vibration. The aim of the study was to analyze the dependence of vibration-mediated changes in some parameters of myocardial tissue respiration on vibration physical characteristics and to justify the role of bioenergetic hypoxia in pathophysiological mechanisms of the interaction of tissue energy metabolism and a physical factor.

Methods. The endogenous mitochondrial respiration rate and sensitivity to inhibitors (amytal, malonate) in tissue homogenate were studied by polarography using a closed galvanic oxygen sensor (Clark).

Results. Multiple comparison of the ETC kinetics revealed a significant effect of 44 Hz frequency vibration on the endogenous substrate oxidation rate in myocardial mitochondria. With a cell protein concentration of 2,4 mg/ml (standart deviation 0,4), the endogenous respiration rate in [ng-atom⸳Omin^-1mg^-1protein] was 16.3 in control animals with predominating amytal-sensitive respiration; 25.9 with predominating malonate sensitive respiration after 21 sessions; and 17.9 after 56 vibration sessions. Modeling of mitochondrial metabolic state gradations using exogenous oxidation substrates and the 2,4-DNF protonophore disassembler confirmed the preferential activation of succinate-dependent myocardial energetics under the conditions of prolonged vibration exposure.

Conclusion. The analysis of the endogenous respiration rate in myocardial homogenate mitochondria showed that specifically the interaction of several variable characteristics of vibration most significantly contributed to the intergroup variability of endogenous substrate oxidation rates. This interaction revealed signs of bioenergetic hypoxia and allowed analyzing the transformation of energy of the primary physical phenomenon into a biological effect. The obtained bioenergetic parameters (Vend, endogenous respiration sensitivity to inhibitors; malonate to amytal sensitivity ratio; V_sa and V_glu+mal; V_sa-c and V_glu+mal-c), that reflect the volume of high-energy phosphates, availability of energy metabolites, and the quantitative ratio of respiratory enzymes that perform ADP phosphorylation, can be used as variables in adequate mathematical models.

Index assessment of parameters of the cardiovascular system functioning in post-stroke patients

Kirill Petrovich Ivanov, Vladimir Terentyevich Dolgikh — Tue, 30 Sep 2025 00:00:00 +0300

Introduction. Objective characteristics of the cardiovascular system (CVS) functioning are important indicators of the physiological state and adaptive reserves of the human body. Aim. Index assessment of the state of peripheral circulation and parameters of the balance between the CVS cardiac and vascular components during the 2nd stage of rehabilitation in patients after ischemic stroke depending on their gender and age.

Methods. The CVS functional state was studied in 66 patients aged 41 to 83 years at the 2nd stage of rehabilitation after ischemic stroke. The patients underwent a rehabilitation program daily for 2 weeks, including exercise therapy using additional mechanical therapeutic devices, therapeutic massage, equipment-based physiotherapy, and drug therapy. On days 1 and 10 of the rehabilitation treatment, daily Holter monitoring of electrocardiogram and blood pressure was performed. Heart rate (HR) and blood pressure (BP) parameters were recorded. To assess the dynamics of the CVS functional state and adaptive potential, CVS function indices were calculated.

Results. An integrated assessment of the CVS functional state allows analyzing the mobilization of the body's adaptive capabilities during rehabilitation treatment. The values of the physiological normal range of hemodynamic indices were calculated as the proper total and specific peripheral vascular resistance (PTPVR and SPVR), proper minute blood volume and cardiac index (PMBO and CI), indices of cardiac function and vascular tone (ICF and IVT), and the integral indicator of the balance of the cardiac and vascular components (IBCVC). Statistically significant (p<0.05) decreases in TPVR and CTVR and an increase in PTPVR were observed. In the total group (n=66), a positive trend in the CVS functioning was noted in 83.33% of cases.

Conclusion. The use of indices for integrated assessment of the CVS functional state during post-ischemic stroke rehabilitation is relevant and pathogenetically justified. In general, there was a tendency for positive dynamics of CVS functioning and its adaptive potential that confirmed the effectiveness of the rehabilitation activities. The above assessment methods can be proposed for monitoring the effectiveness of rehabilitation in post-stroke patients and for scheduling rehabilitation measured at stage 3.

A biopotential-mediated approach to studying the effects of a benzimidazole derivative with 5-HT2A antagonist activity and evaluating its antipsychotic effects in the neonatal ventral hippocampal lesion model in rats

Konstantin Yurievich Kalitin, Olga Yurievna Mukha, Victor Borisovich Voynov — Tue, 30 Sep 2025 00:00:00 +0300

Introduction. In recent years, the role of the serotonergic system in the pathogenesis of schizophrenia has been extensively studied with a particular focus on 5-HT2A receptors as pharmacological targets.

The aim of the study was to evaluate the antipsychotic activity of the novel benzimidazole derivative, RU-31, with a 5-HT2A antagonist activity by analysis of brain bioelectrical activity and behavioral tests in a rat model of psychosis induced by neonatal ventral hippocampal lesions.

Methods. Rats (250-290 g) were implanted with electrodes to record the bioelectrical activity of the brain. Data were processed using a convolutional autoencoder, and the UMAP algorithm, and distances between signal clusters in the parametric space were calculated. Changes in the brain activity after the administration of RU-31 were compared with reference drugs (chlorpromazine, haloperidol, clozapine, risperidone, quetiapine, amitriptyline, fluoxetine, paroxetine, escitalopram, ketanserin, cyproheptadine, hydroxyzine, sumatriptan, ondansetron, atropine, suprastin). Psychosis was modeled in rats by bilateral injection of ibotenic acid (1.5 μg) into the ventral hippocampus on postnatal day 7. The following groups were formed: control (saline 10 ml/kg); RU-31 (10 mg/kg); clozapine (7,5 mg/kg), and sham-operated animals. The groups were then evaluated using the open field test, social interaction test, and novel object recognition test.

Results. Analysis of the brain bioelectrical activity showed that RU-31 had a high degree of similarity to both clozapine (similarity coefficient 0.764) and ketanserin (similarity coefficient 0.756). In the open field test, rats with ibotenic acid-induced lesions displayed hyperlocomotion (Me = 98 crossings, IQR = 50, p<0.01). Administration of RU-31 significantly reduced hyperlocomotion (Me = 58, IQR = 38.75, p<0.05), with a comparable effect observed for clozapine (Me = 47, IQR = 40, p < 0.01). In the social interaction test, RU-31 significantly increased the active behavior duration (Me = 227.6 s, IQR = 59.5, p<0.05), whereas clozapine did not induce a statistically significant effect (Me = 152.8, IQR = 91.4, p>0.05). In the novel object recognition test, RU-31 and clozapine enhanced the discrimination index in the long-term retention phase (Me=0.73, IQR=0.34, and Me=0.68, IQR=0.32, p<0.05, respectively).

Conclusion. The findings confirm the antipsychotic potential of RU-31, particularly in addressing negative and cognitive symptoms, suggesting its promise as a candidate for treating refractory psychotic disorders.

Serum markers of general body condition in rats with maxillofacial pain syndrome

Tue, 30 Sep 2025 00:00:00 +0300

Relevance. Recognition of pain and stress presents significant difficulties due to the lack of highly informative, objective criteria for assessing the state of the animal body in experimental algology. Acute pain is a signal of the presence of damage and danger, that performs a protective function. However, chronic pain emerging in pathological conditions is accompanied by structural and functional damage at the molecular level. In pain syndromes, there are changes in hormone levels, disorders of physiological functions (immune and others) that require high energy expenditure, and deceleration of inflammatory reactions. To objectivize the integrative assessment of the mammalian body condition during the development of pain syndrome, we used the detection of serum structural markers with the Lithos System technology. Aim. Revealing specific features of serum markers for general body condition in rats with maxillofacial pain syndrome.

Methods. The study was conducted on 32 female Wistar rats (body weight 252.0±18.0 g). Four experimental groups were formed: M1 and M2, rats injected with sodium monoiodoacetate (16 mg/kg) 0.04 ml into the temporomandibular joint; S1 and S2, rats that received an intra-articular injection of saline 0.04 ml. In rats of groups M1 and S1, blood for the study was collected on day 14, and in groups M2 and S2, on day 28 after the injection. Blood serum was studied by cuneiform dehydration using the Lithos System technology.

Results. Rats with experimental pain syndrome were characterized by a shift in the expression degree of the systemic indicators for the structural organization of serum facies, “harmony” and “energetics”, towards moderate and low values compared with the control. Those changes are most pronounced at relatively early stages of observation, namely, two weeks after the sodium monoiodoacetate injection into the temporomandibular joint. In animals with induced pain syndrome, high expression of the “stress” marker was observed at late terms of the study, at 4 weeks after intra-articular injection of sodium monoiodoacetate. The number of rats with the presence of the “fibrosis” marker in serum facies two weeks after the sodium monoiodoacetate injection into the temporomandibular joint was greater than at the end of the 4^th week of observation. These features may be related with the immune activation during a relatively late period after the induction of pain syndrome, which reduces the intensity of tissue sclerosing.

Conclusion. The method for analyzing the systemic self-organization of non-cellular biological fluids, the “Lithos System” technology, is one of promising approaches to the unbiased assessment of the general state of the body in pain syndromes.

Characteristics of the erythron in rats with experimental benign prostatic hyperplasia

Natalia Viktorovna Tishevskaya, Dmitry Alexandrovich Maksakov — Tue, 30 Sep 2025 00:00:00 +0300

Aim: to determine the features of erythropoiesis in rats with experimental benign prostatic hyperplasia (BPH) induced by long-term sulpiride administration.

Methods. Experimental model of BPH: rats were administered sulpiride 40 mg/kg, IM, daily for 30 days. The peripheral erythron component (erythrocyte and reticulocyte count and erythropoietin level) was determined in the blood. The condition of the central erythron component was assessed by the quantitative and qualitative composition of erythroblastic islets (EI). The total number of EI was counted in a Goryaev chamber. After Pappenheim staining, the EI distribution by maturity classes was examined.

Results. In rats with BPH, the blood serum content of erythropoietin was decreased by 1.3 times, but the count of erythrocytes and reticulocytes did not differ from the control. The total number of EI in the bone marrow of rats with BPH did not differ from the control, but de novo erythropoiesis completely stopped (maturity class 1 EI disappeared). The number of maturity class 2 islets decreased by 3.3 times, and the number of reconstructing islets increased by 1.4 times. Mature EI (class 3 and involuting EI) remained at the control level.

Conclusion. Long-term administration of sulpiride, which induces prolactin hypersecretion, facilitates the stimulation of erythropoiesis reconstruction in the bone marrow, which is apparently caused by tissue erythropoietin produced by bone marrow macrophages. This stimulation of erythropoiesis reconstruction maintains the number of erythrocytes in the peripheral blood of rats with BPH at a physiological level.

The role of microbiota in pathogenesis and pathomorphosis of cystic fibrosis

Tue, 30 Sep 2025 00:00:00 +0300

The review presents current ideas about the lung microbiota and its important role at different stages of the development of cystic fibrosis, a severe hereditary disease. Just 20 years ago, cystic fibrosis was a fatal disease, but now it demonstrates a tendency towards pathomorphosis, since it becomes a controllable pathology due to basic and targeted pathogenetic therapy. Dysbiosis of the microbial community directly involved in the cystic fibrosis vicious cycle plays a leading role in clinical manifestations of the disease, primarily in the pathology of the respiratory system. New molecular sequencing methods have made it possible to decipher the complex dynamic picture of the respiratory tract microbiome in patients of different age categories. This allowed creating models that most accurately describe the stages of microbiota development depending on the stage of the disease.

Studying pathogenic microbial communities, correlations of their composition with the clinical status of patients, and effects of modulators of the function of the transmembrane regulator of cystic fibrosis open new opportunities in the search for specific biomarkers of the disease to provide an objective prognosis assessment for each patient. Despite its monogenic hereditary nature, cystic fibrosis is a multifactorial disease, in which the interaction of the patient's genotype with the microbiome determines the spectrum of clinical manifestations and the effectiveness of basic and targeted therapy.

Some aspects of the pathophysiology of rheumatoid arthritis.

Anna Yakovlevna Rykunova, Yakov Fedorovich Zverev — Tue, 30 Sep 2025 00:00:00 +0300

The review is devoted to the analysis of the main mechanisms of development of rheumatoid arthritis (RA). Chronic inflammatory process and local hypoxia of synovial tissues require an increased supply of oxygen, which necessitates the formation of new capillaries. A number of proangiogenic factors are activated, including vascular endothelial growth factor (VEGF), adhesion molecules, proinflammatory cytokines, chemokines, and matrix metalloproteinases. Under their influence, the proliferation of endothelial cells occurs, the formation of tubular structures associated with the basement membrane, and the formation of a new primitive vascular network. Mitochondrial dysfunction (MD) plays an important role in RA. Mitochondria at the site of inflammation provide the cell with increased production of energy and reactive oxygen species (ROS). In RA conditions, hypoxia, increased mitochondrial DNA (mtDNA) mutation rates, and excess ROS production are likely to initiate MD. This leads to the activation of autophagy, the formation of the NLRP3 inflammasome, and the release of aberrant mtDNA into the cytosol through a pore that opens in the outer mitochondrial membrane. Emitted mitochondrial structures are sensed as damage-associated molecular patterns (DAMPs), which activate an autoimmune inflammatory process. Activation of free radical oxidation is of great importance in the pathogenesis of RA. With developing hypoxia in the cells of the inflammatory focus, the balance of oxidative and antioxidant factors shifts towards excessive formation of ROS, which leads to the activation of T- and B-lymphocytes, macrophages, and promotes the formation of extracellular traps of neutrophils. All this significantly stimulates the course of autoimmune inflammation. Stimulation of the functional activity of fibroblast-like synoviocytes by free radicals enhances their production of pro-inflammatory cytokines, increases invasiveness and delays the apoptosis of these cells. In addition, excessive activation of radical oxidation contributes to articular cartilage damage and bone erosion through the activation of enzymes that degrade cartilage and extracellular bone matrix. The resulting imbalance between osteoblasts and osteoclasts in favor of the latter induces the process of bone resection.

Liquid biopsy: Prospects for use in patients with malignant melanoma

Ekaterina Yurievna Sergeeva — Tue, 30 Sep 2025 00:00:00 +0300

Liquid biopsy is a method that has been frequently used in recent years as an alternative to traditional tissue biopsy. Liquid biopsy has a number of advantages, including non-invasiveness, a shorter analysis time, high sensitivity, and the opportunity of monitoring of tumor evolution and heterogeneity and real-time drug effectiveness. The use of liquid biopsy is especially important in malignancies, including melanoma, where traditional biopsy may be difficult. The aim of the review is to summarize the information about various methods of liquid biopsy and to assess the advantages and disadvantages of using circulating tumor cells, circulating tumor DNA and extracellular vesicles in this method. The materials were the data reported by Russian and international studies as well as our data published during the past 27 years, from 1997 through 2024. The article summarizes modern data on different types of liquid biopsy. The method of liquid biopsy uses circulating tumor cells, circulating tumor DNA, and extracellular vesicles. The review addresses modern methods of circulating tumor cell isolation and further DNA, RNA and proteome analysis. Also, this review focuses on modern methods of circulating DNA detection and their advantages and disadvantages. Extracellular vesicles are heterogeneous, as secreted by various cells and protected from the external environment by a double lipid membrane. The use of extracellular vesicles for liquid biopsy requires their isolation followed by analysis of their content, proteins and nucleic acids. The review discusses the most effective modern methods of extracellular vesicle isolation and analysis along with the advantages of their use for liquid biopsy. Thus, the use of liquid biopsy can help solving various tasks in diagnostics and treatment of patients with malignant tumors, including melanoma.

Biological significance of the presence of lymphocytes in semen. A hypothesis.

Nina Mikhailovna Gevorgyan — Tue, 30 Sep 2025 00:00:00 +0300

The article proposes a solution to a still unclear problem of the so-called "immune paradox of pregnancy" and the nature of tolerance to a semi-allogeneic fetus. A comprehensive analysis of a wide range of functional effects that we have identified in various studies of the inductive, therapeutic and prophylactic action of exogenous total RNA of lymphoid cells from healthy individuals in vivo, as well as the ability of total RNA of morphogenetic γδ-T-lymphocytes to reprogram and normalize pathological processes, has allowed us to reveal and clarify the true strategy of the effects of sperm components during fertilization. Thus, the obtained speculative picture appeared an exceptionally clear demonstration of the organization principle of evolving systems formulated in 1965 by V.A. Geodakyan. The principle is the asynchronous evolution of binary-conjugated subsystems, and it also harmoniously agrees with the unique observations and an exceptionally bold conclusion of A.A. Maksimov (1909) that "in the body of mammals there is one type of cells, lymphocytes ... which, depending on the diversity of their living conditions in the body of the embryo, look different and can produce different cells, products of differentiation." Finally, the concept proposed here allows answering the question of the origin of T-lymphocyte precursors in the embryogenesis of the thymus, which has not yet been resolved.