We studied cytotoxicity and the effect on cell viability in in vitro incubated mammalian embryonic cells of purine derivative aminophylline, indole derivative ergotamine tartrate, as well as the phosphoric acid derivatives 3-ethyl-2-hydroxy-2-oxa-1,4,2-oxazaphosphorinane (EHOOP) and α-ethyl-α-N-(hydroxyethylamino)methylphosphonic acid (ENHEAMPA) after inoculation of the cells with vaccine avipoxviral strain FK (fowl) with initial infectious titer 106 CCID50/ml for 24 or 48 h. The tested substances were applied for 24 or 48 h at concentrations of 10-11-10-2 mol/ml (aminophylline and ergotamine tartrate), as well as at 10-11-10-3 mol/ml (EHOOP and ENHEAMPA). In cell suspensions, the cytotoxic concentrations CC50 (mol/ml) were determined corresponding to the death or alterations in half of the cells. They were 10-3 and 10-2 mol/ml for purine and indole analogues, respectively, whereas similar values for two phosphoric acid derivatives were 10-5-10-4 mol/ml. At low concentrations of the test substances, a decrease in cell viability was observed when exposure was prolonged from 24 to 48 h, which can be explained by pathogenic action of the inoculated virus. A decrease in cell viability was also observed when the concentration of the test agents was elevated, which can be explained by their intrinsic cytotoxic action at high concentrations. Overall, purine and indole analogues were less toxic for cultured mammalian cells than the test phosphoric acid derivatives. Purine analogue aminophylline had the lowest cytotoxicity, but exhibited maximum antiviral activity.

Na,K-ATPase activity is critical for maintaining electrogenesis and skeletal muscle function. Isolated rat diaphragm muscles were studied after 3-h high-altitude hypobaric hypoxia (HAH, corresponds to an altitude of 6000 m) in a pressure chamber. LPO activation was observed over 24 h after HAH; no significant changes in other markers of oxidative stress and energy metabolism were detected. During this period, stable hyperpolarization of the sarcolemma developed due to increased electrogenic activity of the α2-Na,K-ATPase isoform, while the total muscle level of the α2-subunit protein remained unchanged. Our findings may have practical implications for developing measures to maintain skeletal muscle functions during high-altitude adaptation.

Listeria monocytogenes, a causative agent of sapronoses, can enter the human body through ingestion of contaminated marine hydrobionts, posing a significant public health risk. Mono- and polycultural biofilms of microorganisms were detected spectrophotometrically. The study demonstrated that metabolites from marine-origin Bacillus bacteria stimulate the formation of L. monocytogenes monocultural biofilms, as well as mixed biofilms of L. monocytogenes and the marine bacterium Micrococcus luteus. In mixed biofilms of L. monocytogenes and a marine Flavobacterium bacterium genus, Bacillus megaterium metabolites exhibited both stimulating and inhibitory effects, depending on concentration. These findings suggest that Bacillus-derived metabolites can enhance the growth and proliferation of L. monocytogenes in biofilms, potentially influencing the epidemic risks in recreational areas of Peter the Great Gulf.

The growth-stimulating effect of platelet lysates obtained after exposure of platelet suspension to low-pulse laser radiation (LPLR) with λ = 470 nm (blue laser) and λ = 635 nm (red laser) was studied in a culture of human M-22 fibroblasts. LPLR-irradiated platelet suspension in plasma and plasma-free medium reduced the content of platelets with granules by 5-7% at λ = 470 nm and 25-27% at λ = 635 nm (p < 0.05). In presence of platelet lysates, the number of fibroblasts significantly increased by 1.3-1.4 times after 3 days of cultivation. In experiments with platelets in plasma-free medium, the samples previously irradiated at λ = 470 nm produced a lower growth-stimulating effect, than samples irradiated at λ = 635 nm and non-irradiated samples; for platelets irradiated in autologous plasma, no prominent differences were observed. Lysates of LPLR-irradiated platelets did not impair structural integrity of human fibroblasts in culture.

The correlation between the products of oxidative modification of lipids, proteins, DNA and sleep quality and the presence of the methanogen Methanosphaera stadtmanae in the intestine was assessed in 98 menopausal women. Higher levels of thiobarbituric acid-reactive substances (TBARS) and end-products of protein oxidation were found in the group with sleep disorders (Pittsburgh Sleep Quality Index) in comparison with the control in the sample with M. stadtmanae in the intestine. The presence of this microorganism is associated with a lower level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the total sample, as well as in the control group, while for the group with sleep disorders, M. stadtmanae is associated with a higher level of TBARS and Schiff bases. The results indicate possible interaction between M. stadtmanae from the intestine and oxidative processes in the body.

Male Wistar rats were subjected to mild, moderate, and heavy physical exercises (10 swimming sessions), after which they were euthanized (immediately or 30 days after the last session). Animals of the experimental groups received meldonium (100-120 mg/kg of body weight) with food for 10 days of swimming. Heavy exercise led to the development of degeneration, necrotic patches, and cellular infiltration in the liver and a decrease of the TGF-β1 level. In 30 days after the last swimming session, an increase in both the level of TGF-β1 in the cytoplasmic fraction and the expression of the tgfb1 gene were observed. The level of TGF-β1 increased by 1.8 times against the background of meldonium treatment and decreased by 1.6 times in 30 days; tgfbl expression also decreased by 1.3 times in comparison with that in rats exposed to a similar exercise without meldonium (p < 0.05). The use of meldonium against the background of heavy physical exercise contributed to the achievement of gene expression and cytokine levels approaching the target values observed in intact animals and prevent severe alterative changes in the liver.

Лёгочная артериальная гипертензия (ЛАГ) характеризуется нейрогуморальным дисбалансом. Изучено влияние ЛАГ на транскрипционную активность в препаратах лёгочной артерии. У крыс с ЛАГ, индуцированной монокроталином (60 мг/кг), выделяли препараты лёгочной артерии с последующим полнотранскриптомным РНК-секвенированием. Определяли индекс обогащения генных коллекций баз Gene Ontology и KEGG. Значимые коллекции объединяли в кластеры, для которых выявляли гены с наибольшими изменениями экспрессии и представленностью в коллекциях. У ключевых генов определяли представленность функциональных доменов в белковых последовательностях. ЛАГ приводит к значимому росту индекса обогащения коллекций, связанных с сократительными элементами и цитоскелетом мышечных клеток (в том числе кардиомиоцитов), и снижению такового для коллекций, связанных с синтезом рибосомных компонентов. Кластеризация путей позволила выявить изменения экспрессии генов, характерные для нарушения тиреоидной сигнализации.

Методами поляризационной микроскопии и трансмиссионной электронной микроскопии исследован сократительный аппарат кардиомиоцитов левого желудочка сердца преждевременно рождённых (на 1 сут раньше срока) 180-дневных крыс. В кардиомиоцитах преждевременно рождённых крыс миофибриллы неоднородны по толщине: наряду с истончёнными и дискомплексированными участками миофибрилл определяются утолщённые миофибриллы. Лизис миофибрилл преимущественно мелкоочаговый, реже — диффузный. Наблюдаются кардиомиоциты с субсегментарными контрактурами. В кардиомиоцитах преждевременно рождённых крыс выявляются митохондрии с признаками деструкции, в расширенных межмиофибриллярных пространствах — многочисленные мелкие митохондрии, не формирующие межмитохондриальных контактов. Повреждение митохондрий приводит к структурным и функциональным нарушениям сократительного аппарата кардиомиоцитов.

Using zebrafish (Danio rerio) as a model organism, we studied metabolomic markers of β-blocker neurotoxicity (propranolol, metoprolol, bisoprolol) and the relationships between neurotransmitter disturbances (dopamine, epinephrine, choline, cortisol) and their effects. Propranolol produced the most pronounced changes: significant increases in cortisol and epinephrine and decreases in dopamine and serotonin levels. Metoprolol caused a moderate increase in cortisol while elevating serotonin, suggesting a more balanced pharmacological profile. Bisoprolol had virtually no effect on cortisol or monoamine levels but increased the concentrations of choline, glycine, and glutamate. Differences in neurometabolic effects of β-blockers were identified: propranolol demonstrated a strong neurotoxic potential, consistent with its depressive side effects in humans; metoprolol showed an intermediate effect; while bisoprolol did not affect CNS. Zebrafish exhibited high sensitivity to neurochemical shifts, making this model valuable for preclinical drug neurotoxicity assessment.