Coronary artery disease (CAD) and the coronary artery bypass graft (CABG) are associated with a decreased blood glutathione (bGSH) level. Since GSH metabolism is closely related to other aminothiols (homocysteine and cysteine) and glucose, the aim of this study was to reveal the associations of bGSH with glucose and plasma aminothiols in CAD patients (N = 35) before CABG and in the early postoperative period. Forty-three volunteers with no history of cardiovascular disease formed the control group. bGSH and its redox status were significantly lower in CAD patients at admission. CABG had no significant effect on these parameters, with the exception of an increase in the bGSH/hemoglobin ratio. At admission, CAD patients were characterized by negative associations of homocysteine and cysteine with bGSH. All these associations disappeared after CABG. An association was found between an increase in oxidized GSH in the blood in the postoperative period and fasting glucose levels. Thus, CAD is associated with the depletion of the intracellular pool and the redox status of bGSH, in which hyperhomocysteinemia and a decrease in the bioavailability of the extracellular pool of cysteine play a role. The present study indicates that CABG causes disruptions in aminothiol metabolism and induces the synthesis of bGSH. Moreover, glucose becomes an important factor in the dysregulation of GSH metabolism in CABG.

Platelets are one of the main participants in vascular accidents in cases of coronary heart disease (CHD). In this study, we sought to detect platelet apoptosis in patients with coronary artery disease who underwent scheduled myocardial revascularization surgery. To identify apoptotic events, we analyzed phosphatidylserine (PS) expression on the surface of platelets and mitochondrial membrane potential (ΔΨm) by flow cytometry in two groups of 30 patients aged 45–60 years: Group 1—patients before myocardial revascularization surgery and group 2—patients after myocardial revascularization surgery. The control group consisted of 10 healthy volunteers aged 45–60 years. According to our data, the percentage levels of PS expression in patients greatly decreased after surgery. We confirmed platelet apoptosis by recording depolarization of ΔΨm in pre- and postoperative patients. ΔΨm readings were considerably improved after surgery. Our data indicated that the functional parameters of platelets in patients with coronary heart disease differed from the characteristics of platelets in patients who underwent myocardial revascularization, and from those of patients in a control group. Future studies of platelet phenotypic characteristics and platelet apoptosis biomarkers should greatly advance our understanding of the pathophysiology of coronary heart disease, and further promote the development of methods for predicting adverse outcomes after surgery.

The study of the physiological and pathophysiological processes under extreme conditions facilitates a better understanding of the state of a healthy organism and can also shed light on the pathogenesis of diseases. In recent years, it has become evident that gravitational stress affects both the whole organism and individual cells. We have previously demonstrated that simulated microgravity inhibits proliferation, induces apoptosis, changes morphology, and alters the surface marker expression of megakaryoblast cell line MEG-01. In the present work, we investigate the expression of cell cycle cyclins in MEG-01 cells. We performed several experiments for 24 h, 72 h, 96 h and 168 h. Flow cytometry and Western blot analysis demonstrated that the main change in the levels of cyclins expression occurs under conditions of simulated microgravity after 96 h. Thus, the level of cyclin A expression showed an increase in the RPM group during the first 4 days, followed by a decrease, which, together with the peak of cyclin D, may indicate inhibition of the cell cycle in the G2 phase, before mitosis. In addition, based on the data obtained by PCR analysis, we were also able to see that both cyclin A and cyclin B expression showed a peak at 72 h, followed by a gradual decrease at 96 h. STED microscopy data also confirmed that the main change in cyclin expression of MEG-01 cells occurs at 96 h, under simulated microgravity conditions, compared to static control. These results suggested that the cell cycle disruption induced by RPM-simulated microgravity in MEG-01 cells may be associated with the altered expression of the main regulators of the cell cycle. Thus, these data implicate the development of cellular stress in MEG-01 cells, which may be important for proliferating human cells exposed to microgravity in real space.

Цель работы: изучить динамику состояния клеток крови и костного мозга при прогрессирующем развитии сахарного диабета 2 типа (СД2) в зависимости от степени тяжести нарушений окислительно-восстановительных процессов (ОВП) в тканях организма. Методика. Использована генетическая модель СД2 у мутантных мышей – db/db (опытная группа n=30). Контролем слу жили здоровые мыши той же линии – db/+m (n=10) и линии B10 (n=5). В течение 6–6,5 мес контролировали: динамику кли нических показателей (глюкоза крови, гликозилированный гемоглобин, масса тела) и состояние ОВП в тканях организма по уровню активности НАДН, ФАД и показателю окислительного метаболизма (ПОМ) с помощью аппарата «Лазма-СТ». В течение того же срока исследовали состояние клеток крови (эритроциты, лейкоциты, тромбоциты) и костного мозга. Ста тистическую обработку результатов проводили с предварительным использованием теста Шапиро–Уилкса; достоверность различий с контролем оценивали с помощью параметрического t – критерия Стьюдента, при р<0,05. Результаты. В развитии СД2 выявлено 3 стадии прогрессирующего нарушения метаболизма и ОВП: I – стадия адаптации (1,0-2,0 мес); II – стадия прогрессирующей дисадаптации (2,5-4,5 мес); III – стадия декомпенсации (5,0-6,5 мес). Установлено, что уже в I стадии у мышей db/db снижалось содержание эритроцитов, Hb г/л и лейкоцитов. Во II и особенно в III стадиях происходило повышение тромбоцитов, нейтрофилов, моноцитов, эозинофилов, снижение лимфоцитов. В костном мозге у мышей db/db уже в I, но особенно в III стадии определялось снижение доли живых и повышение количества поврежден ных клеток, преимущественно за счёт апонекротических клеток. Заключение. По мере прогрессирования СД2 и выраженного снижения эффективности ОВП, особенно на III стадии – в организме тормозятся процессы кроветворения и усиливаются нарушения в соотношении клеточных популяций нейтро филы/лимфоциты, что свидетельствует о развитии тяжёлой гипоксии, активации системной воспалительной реакции и торможении репаративных процессов, создающих условия для развития опасных осложнений. Aim: to study the dynamics of changes in the blood and bone marrow cells during the progression of type 2 diabetes mellitus (DM2) depending on the severity of redox (RO) disorders in tissues. Methods. A genetic model of DM2 in mutant db/db mice (experimental group, n=30) was used. The control group consisted of the same mouse strain, db/+m (n=10), and the B10 strain (n=5). Time-related changes in clinical variables (blood glucose, HbA1c, body weight) and the tissue RO status were monitored for 6-6.5 months. The RO status was evaluated by the NADH concentration, FAD activ ity, and the indicator of oxidative metabolism (IOM) using a Lasma-ST apparatus. During the same period, the condition of blood cells (erythrocytes, leukocytes, platelets) and bone marrow cells was examined. Statistical analysis was performed with a preliminary Shap iro-Wilks normality test followed by the parametric Student’s t-test. Differences from the control were considered significant at p<0.05. Results. During the development of DM2, three stages of progressive metabolic and RO disorders were identified: I: stage of adap tation (1.0-2.0 months); II, stage of progressive maladaptation (2.5-4.5 months); III, stage of decompensation (5.0-6.5 months). In db/db mice already at stage I, erythrocytes, Hb and leukocytes were decreased. At stages II and especially III, platelets, neutrophils, monocytes, and eosinophils were increased whereas lymphocytes were reduced. In the bone marrow of db/db mice, already in stage I, but even more in stage III, the proportion of living cells was decreased and the proportion of damaged cells was increased, primarily due to the contribution of aponecrotic cells. Conclusion. With the progression of DM2 and a pronounced decrease in the effectiveness of RO processes, especially at stage III, the hematopoietic processes were inhibited and the disorders in the neutrophil/lymphocyte cell population ratio intensified. This indicates the development of severe hypoxia, activation of a systemic inflammatory response, and inhibition of reparative processes that create conditions for development of dangerous complications.

Актуальность. Исследования, выполненные в невесомости, показали, что космический полет вызывает серьезные физиологические изменения в живом организме. В клетках млекопитающих микрогравитация способна индуцировать и модулировать протекание таких ключевых процессов, как апоптоз, пролиферация, миграция и адгезия. Несмотря на возросший интерес к космической биологии и медицине, исследования клеточного цикла в условиях микрогравитации остаются спорными. Цель исследования – изучение экспрессии циклинов клеточного цикла клеток мегакариобластного лейкоза человека при воздействии моделированной микрогравитации. Методика. Для экспериментов клетки мегакариобластного лейкоза человека (MEG-01) высевали в культуральные флаконы. Условия микрогравитации моделировали с использованием прибора случайного позиционирования (RPM – Random Positioning Machine). Клетки размещали в центре платформы прибора случайного позиционирования (группы RPM) и сравнивали со статической контрольной группой (1g). Анализ экспрессии циклинов клеточного цикла проводили методом вестерн блота и на проточном цитофлоуриметре. Результаты. Результаты исследований показывают, что под воздействием микрогравитации клетки мегакариобластного лейкоза человека MEG-01 демонстрируют сопоставимые уровни экспрессии циклина D и E при сравнении с контрольной группой. Однако, уровни циклинов A и B повышались в течение первых 96 ч. В дальнейшем, количество этих циклинов снижалось к 168 ч в сравнении с предыдущей временной точкой и контрольной группой. Заключение. Таким образом, на основе полученных данных можно сделать заключение, что клетки MEG-01, подверженные RPM-моделированной микрогравитации успешно входят в клеточный цикл и завершают синтетическую фазу, но останавливаются в фазе G2 и не способны завершить митоз. Однако в более поздние сроки (168 ч) клетки MEG-01 успешно адаптируются к условиям невесомости. Результаты согласуются с экспериментальными данными, полученными при исследовании различных типов клеток при различных способах моделирования микрогравитации. Дальнейшие исследования влияния гравитации на клеточные реакции мегакариоцитов помогут понять патогенез заболеваний человека, приобретенных в экстремальных условиях. Background. Studies of weightlessness have shown that space flight causes serious physiological changes in a body. In mammalian cells, microgravity is able to induce and modulate key processes such as apoptosis, proliferation, migration, and adhesion. Despite growing interest to space biology and medicine, reports of cell cycle in microgravity remain controversial. Aim. This paper analyzes the expression of cell cycle cyclins in human megakaryoblastic leukemia cells exposed to simulated microgravity. Methods. Human megakaryoblastic leukemia (MEG-01) cells were seeded in culture flasks. Microgravity conditions were simulated using a Random Positioning Machine (RPM). Cells were placed at the center of the platform of the RPM (RPM group) and compared with a static control group (1 g). Cell cycle cyclin expression was analyzed by Western blotting and with a flow cytometer. Results. In the conditions of microgravity, MEG-01 showed comparable expression levels of cyclins E and D vs. the control group. However, concentrations of cyclins A and B increased during the first 96 h. Subsequently, concentrations of these cyclins decreased by 168 h compared to the previous time point and the control group. Conclusion. This study allowed a conclusion that MEG-01 cells exposed to RPM-modeled microgravity start proliferating and successfully finish the synthetic phase but stop in the G2 phase being unable to complete mitosis. However, at a later time (168 h), MEG-01 cells successfully adapt to the weightlessness conditions. In addition, the results are also consistent with reports of experiments on various cells under different conditions of simulated microgravity. Further studies of the effect of gravity on responses of megakaryocytes will provide insight into pathophysiology of human diseases acquired in extreme conditions.

Crohn's disease (CD) is a chronic inflammatory bowel disorder driven by dysregulated immune responses, epithelial barrier dysfunction, and progressive tissue damage. Despite advances in biologic therapies, treatment resistance and loss of response remain common. The activating receptor NKG2D, expressed on natural killer cells and T cell subsets, recognizes stress-induced ligands (MICA, MICB, ULBP) upregulated on intestinal epithelial cells under inflammatory conditions. In CD, sustained ligand expression promotes NKG2D-dependent cytotoxicity, pro-inflammatory cytokine release (IFN-γ, IL-17), and lymphocyte trafficking into the mucosa, perpetuating a cycle of epithelial injury and chronic inflammation. Preclinical colitis models and clinical trials with anti-NKG2D monoclonal antibodies (e.g., NNC0142-0002) demonstrate reduced disease activity, improved histological outcomes, and induction of remission in moderate-to-severe CD patients. However, challenges remain, including potential impairment of immune surveillance against infections and tumors, patient heterogeneity, and pathway redundancy. Future directions include biomarker-guided patient selection, combination therapies with anti-TNF or anti-integrin agents, and next-generation biologics such as bispecific antibodies. Understanding the cellular and molecular basis of NKG2D signaling in mucosal inflammation positions this receptor as a promising, mechanistically anchored therapeutic target in Crohn's disease.