[Hypoxic training in rehabilitation of patients at the early stages of recovery after SARS-CoV-2 pneumonia]. / Rol' gipoksicheskikh trenirovok v reabilitatsii patsientov na rannikh srokakh vosstanovleniya posle pnevmonii, vyzvannoi virusom SARS-CoV-2.

OBJECTIVE: To evaluate efficacy and safety of hypoxic-hyperoxic therapy in rehabilitation after SARS-CoV-2 pneumonia. MATERIAL AND METHODS: There were 44 patients aged 49-75 years in early recovery period after previous SARS-CoV-2 pneumonia (ICD-10 U07.1 and U07.2). Patients were divided into 2 groups depending on treatment strategy: group 1 (n=23) - rehabilitation treatment with therapeutic exercises, massage and physiotherapy; group 2 (n=21) - basic procedures with hypoxic-hyperoxic therapy. RESULTS: At initial evaluation, we found positive tendencies of rehabilitation in both groups. There were no side effects associated with hypoxic-hyperoxic therapy in the second group. Patients positively perceived this method of rehabilitation. There were significant between-group differences in exercise tolerance (p<0.05). These data indicate more favorable physical recovery in the second group and similar improvement of psycho-emotional status in both groups. CONCLUSION: Hypoxic-hyperoxic therapy is effective and safe approach in rehabilitation of patients with previous SARS-CoV-2 pneumonia. It is necessary to continue searching for effective methods of rehabilitation and develop accurate rehabilitation methods for various groups of patients.

[The role of systemic ozone therapy in the rehabilitation of patients after COVID-19]. / Rol' sistemnoi ozonoterapii v reabilitatsii patsientov, perenesshikh COVID-19.

OBJECTIVE: To evaluate the effectiveness and safety of ozone therapy in rehabilitation of patients with previous COVID-19. MATERIAL AND METHODS: A randomized controlled clinical trial included 51 patients aged 29 - 78 years with SARS-CoV-2 pneumonia (J12.8). Patients were divided into 3 comparable groups depending on the complex of rehabilitation. In the first (control) group (n=17), a 10-day course included daily breathing exercises and physiotherapy for the lungs (drug electrophoresis and low-frequency magnetotherapy). In the second (main) group (n=18), rehabilitation was combined with daily intravenous infusions of ozonized saline with ozone concentration of 2.0 mg/l within 5 days with subsequent standard rehabilitation. In the third group (n=16), patients received 5 ozone therapy procedures every other day. To determine the effectiveness and safety of systemic ozone therapy in rehabilitation of patients with previous COVID-19, we analyzed oxygen saturation, laboratory data (D-dimer and C-reactive protein), need for oxygen support before and after rehabilitation course. Complaints and quality of life throughout the rehabilitation program were assessed using the EQ-5D questionnaire. RESULTS: All patients had positive changes of all parameters. There were no adverse reactions throughout the rehabilitation program and 2 months later. We observed higher effectiveness of rehabilitation with systemic ozone therapy. Moreover, daily ozone therapy had a better effect on laboratory parameters compared to ozone therapy every other day. CONCLUSION: Ozone therapy is safe and effective in complex rehabilitation of patients with previous COVID-19. Further studies of large samples are needed to determine indications and appropriate criteria for this rehabilitation program.

[Comprehensive rehabilitation of immune-mediated adverse events in cancer patients receiving checkpoint inhibitor therapy]. / Kompleksnaya reabilitatsiya immunooposredovannykh nezhelatel'nykh yavlenii u patsientov so zlokachestvennymi opukholyami, poluchayushchikh terapiyu ingibitorami kontrol'nykh tochek.

OBJECTIVE: To evaluate adverse events and clinical effectiveness of complex rehabilitation programs in patients with malignant tumors receiving checkpoint inhibitor therapy. MATERIAL AND METHODS: The study included 144 cancer patients who received immunotherapy for the period from 2019 to 2021. Group 1 consisted of 72 patients who received a comprehensive rehabilitation program including physical therapy, diet therapy, psychotherapy, general magnetotherapy. Patients of the second (control) group (n=72) did not receive rehabilitation procedures. Effectiveness of treatment was evaluated according to RECIST 1.1 criteria, safety of treatment - according to CTCAE criteria (version 5.0, 2017). To assess the quality of life (QoL), the Russian version of the EORTC QLQ-C30 questionnaire was used. RESULTS: Mean follow-up period in the first group was 4.5 months, in the control group - 5 months. Disease progression was observed in 35 (48.6%) patients of the main group and 32 (44.4%) patients of the control group. Two (2.8%) patients in the control group demonstrated complete response to therapy. Partial response was established in both groups in 13 patients (18.1%). Stabilization of disease was detected in 24 (33.3%) and 25 (34.7%) patients, respectively. Adverse events were registered in 54 (75.0%) and 60 (83.3%) patients, respectively. Adverse events grade III-IV occurred in 9.7% and 11.1% of patients, respectively. CONCLUSION. I: Mmunotherapy combined with comprehensive rehabilitation program confirms high effectiveness of these drugs. We observed good tolerability of rehabilitation procedures that do not deteriorate the course of the underlying disease. However, there are certain important issues, in particular influence of rehabilitation procedures on tolerability of immunotherapy in patients with cancer.

[Influence of therapeutic exercises and hardware massage in electrostatic field on lung damage in patients with novel coronavirus pneumonia]. / Otsenka vliyaniya lechebnoi gimnastiki i apparatnogo massazha v elektrostaticheskom pole na stepen' porazheniya legkikh u patsientov s pnevmoniei pri novoi koronavirusnoi infektsii.

OBJECTIVE: To analyze the efficacy and safety of therapeutic exercises and chest hardware massage in electrostatic field in patients with COVID-associated viral pneumonia. MATERIAL AND METHODS: We retrospectively analyzed 1551 patients admitted to the Clinical Hospital No. 1 (MEDSI Group JSC) with COVID-associated pneumonia between April 01, 2020 and June 15, 2021 (ICD-10 U07.1 and U07.2). Considering inclusion and exclusion criteria, we enrolled 153 patients. All patients were divided into comparable groups and subgroups depending on the methods of rehabilitation treatment and CT stage of viral pneumonia. Lung damage was assessed semi-automatically using Philips Portal v11 COPD software. Rehabilitation measures included therapeutic exercises and chest hardware massage in electrostatic field. therapeutic exercises. RESULTS: Therapeutic exercises significantly reduced severity of lung damage in patients with viral pneumonia CT-2 and no oxygen support (from 28.05% [28; 29.5] at admission to 15.3% [14.2; 19.3] at discharge). It was not observed in patients without rehabilitation treatment and in patients undergoing therapeutic exercises and massage in electrostatic field. CONCLUSION: Therapeutic exercises in patients with COVID-19 and baseline lung damage > 25% and < 50% (CT-2 stage) significantly reduce severity of lung damage at discharge compared to the control group.

Chondrogeneic Potential of MSC from Different Sources in Spheroid Culture.

We performed a comparative study of the proliferative potential of human mesenchymal stromal cells (MSC) from three sources (tooth pulp, adipose tissue, and Wharton's jelly) in spheroid culture; human chondroblasts served as the positive control. Histological examination revealed signs of chondrogenic differentiation in all studied cell cultures and the differences in the volume and composition of the extracellular matrix. Spheroids formed by MSC from the tooth pulp and Wharton's jelly were characterized by low content of extracellular matrix and glycosaminoglycans. Spheroids from adipose tissue MSC contained maximum amount of the extracellular matrix and high content of glycosaminoglycans. Chondrocytes produced glycosaminoglycan-enriched matrix. Type II collagen was produced by chondrocytes (to a greater extent) and adipose tissue MSC (to a lesser extent). The results of our study demonstrate that MSC from the adipose tissue under conditions of spheroid culturing exhibited maximum chondrogenic potential.

A bright γ-ray flare interpreted as a giant magnetar flare in NGC 253.

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (1014 to 1015 gauss), called magnetars1,3,4. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts5,6, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission7. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares2,8-11. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 1046 erg) is similar to that of the superflare5,12,13 from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 1046 erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.

Expression of Epithelial Cell Adhesion Molecule (EpCAM) in Tumor Spheroids of Human Colorectal Adenocarcinoma Cells.

We studied the formation of spheroids by Caco-2, SW480, and HCT116 human colorectal adenocarcinoma cell lines under low-adhesion culturing conditions. Of these three cell lines, only HCT116 formed stable tumor spheroids. Flow cytometry analysis of 19 surface markers in monolayer HCT116 culture and spheroids formed by these cells revealed considerable similarity of the expression profiles in these two culturing modes. The only exception was EpCAM molecule: its expression in spheroids was 3-fold higher than in the monolayer culture. Scanning confocal laser microscopy showed equal EpCAM distribution in the inner mass of the spheroids.

[Proteomics of transcription factors: identification of pool of HL-60 cell line-specific regulatory proteins]. / Proteomika transkriptsionnykh faktorov: identifikatsiia pula reguliatornykh belkov, spetsifichnykh dlia kletok linii HL-60.

HL-60 promyelocytic cells are a widely used as a model for studying induced granulocytic differentiation. Investigation of proteins of the nuclear fraction, particularly transcription factors, is necessary for a better understanding of molecular mechanisms of cell maturation. Mass spectrometry is a powerful tool for analyzing a proteome due to its high sensitivity, specificity and performance. In this paper, using the selected reaction monitoring (SRM) method, we have assessed the levels of RBPJ, STAT1, CEBPB, CASP3, VAV1, PRKDC, PARP1 and UBC9 nuclear proteins isolated using hypertonic buffer, detergents (sodium dodecyl sulfate (SDS), sodium deoxycholate (DOC) and fissionable detergent ProteaseMAX™) and using centrifugation in a sucrose density gradient. The minimum and maximum protein content was 1.13±0.28 and 14.34±1.63 fmol/mkg of total protein for the transcription factor RBPJ and ubiquitin-protein ligase type I UBC9, respectively. According to the results of shotgun mass spectrometric analysis of nuclear fractions, 2356 proteins were identified, of which 106 proteins were annotated as transcription factors. 37 transcription factors were uniquely identified in the fraction obtained by centrifugation in a sucrose density gradient, while only 9 and 8 transcription factors were uniquely identified in the nuclear fractions obtained using hypertonic buffer and detergents, respectively. The transcription factors identified in the HL-60 cell line represent regulatory molecules; their directed profiling under the influence of differentiation inducers, will shed light on the mechanism of granulocyte maturation.

Proteomic Profiling of HL-60 Cells during ATRA-Induced Differentiation.

Acute promyelocytic leukemia, a form of acute myeloid leukemia, is characterized by cell differentiation arrest at the promyelocyte stage. Current therapeutic options include administration of all trans-retinoic acid (ATRA), but this treatment produces many side effects. ATRA is known to induce differentiation of leukemic cells into granulocytes, but the mechanism of this process is poorly studied. We performed comparative proteomic profiling of HL-60 promyelocytic cells at different stages of ATRA-induced differentiation to identify differentially expressed proteins by high-resolution mass spectrometry and relative quantitative analysis without isotope labels. A total of 1162 proteins identified by at least two unique peptides were analyzed, among them 46 and 172 differentially expressed proteins were identified in the nuclear and cytosol fractions, respectively. These differentially expressed proteins can represent candidate targets for combination therapy of acute promyelocytic leukemia.

[Comparative proteomic profiling of nuclear and cytosolic fractions from cell lines of different origin]. / Sravnitel'noe proteomnoe profilirovanie iadernoi i tsitozol'noi fraktsii kletochnykh linii razlichnogo proiskhozhdeniia.

Proteomic analysis of the nuclear fraction is of great importance, since many cellular processes are initiated in the nucleus. Refinement and choice of experimental procedures for cell lysate fractionation and parameters for mass spectrometric detection and data processing continue to be of current interest. The mass spectrometry analysis presented here was tested on human cell lines derived from different tissues: HL-60 (peripheral blood); HepG2 (liver); EA.hy926 (vascular endothelium). High reproducibility of results and their consistency with biological properties of the objects under study were demonstrated. The use of cells of different types made it possible to reveal a set of 16 proteins whose LFQ-values allow for the discrimination between proteome fractions regardless of cell origin. Also, a set of 16 proteins is suggested which are associated with individual characteristics of cell lines regardless of cell fraction. These protein panels can serve as parameters to verify the proteomic analysis done was of sufficient quality, in particular as indicators of successful fractionation of cell or tissue lysate.

MNT Optimization for Intracellular Delivery of Antibody Fragments.

We studied the possibility of optimizing modular nanotransporters (MNTs) for the intracellular delivery of antibody fragments into the nuclei of cells of a specified type. Basic MNT with a reduced size retaining the desired functions was obtained, and the principal possibility of obtaining an MNT carrying an antibody fragment by microbiological synthesis was shown.

Modular Nanotransporter with P21 Fragment Inhibits DNA Repair after Bleomycin Treatment.

Modular nanotransporter (MNT) with C-terminal fragment of the p21 protein was synthesized and characterized, and its effect on DNA lesions was studied. This p21 fragment in MNT can significantly inhibit DNA repair in A431 human carcinoma cells after bleomycin treatment.

Remodeling of ventricular repolarization in experimental right ventricular hypertrophy.

BACKGROUND: To understand electrophysiological mechanisms that underlie the progression of compensated right ventricular hypertrophy (RVH) to heart failure, the purpose of the study was to evaluate remodeling of ventricular repolarization in connection with hemodynamic abnormalities and vulnerability of the heart ventricles to arrhythmias in RVH rats with pulmonary arterial hypertension (PAH) and heart failure. METHODS: PAH followed by heart failure was induced by monocrotaline in adult female Wistar rats. Unipolar epicardial electrograms and cardiac hemodynamic parameters were recorded in situ. Vulnerability to ventricular arrhythmias was measured as the threshold dose of aconitine required to produce sustained ventricular tachycardia. Histological examination of the heart ventricles was performed. Activation-recovery intervals (ARIs) and ARI dispersions were used as indices of durations and heterogeneity of repolarization respectively to assess ventricular repolarization. RESULTS AND CONCLUSIONS: The development of compensated RVH was characterized by the dramatic prolongation of repolarization against the less expressed increase in repolarization heterogeneity, whereas the dramatic increase in repolarization heterogeneity against the less expressed but inhomogeneous prolongation of repolarization occurred in the progression of compensated RVH to heart failure. These changes increased vulnerability of the failing heart but not the compensated heart to aconitine-induced ventricular arrhythmias.

Characterization of new modular nanotransporters with albumin-binding domain.

The albumin-binding domain (ABD) with a site for its cleavage by tumor proteases was inserted in the structure of modular nanotransporters (MNTs), chimeric proteins for the delivery of anticancer drugs into the nuclei of cancer cells. The effectiveness of this cleavage was tested in both variants of created construct: "pure" ABD-MNT and the complex with albumin. The introduction of the ABD module into MNTs had no effect on the binding of MNT with receptors on the surface of the target cancer cells and on the preferential accumulation of MNTs in the nuclei of these cells. The use of thermophoresis allowed us to determine the equilibrium dissociation constants of the ABD-MNT complex with bovine and human serum albumins.

[ABOUT UNIFICATION OF LABORATORY CRITERIA OF DIFFERENTIATION OF BACTERIAL VAGINOSIS].

The article presents analysis of laboratory criteria and classifcations used to interpret results of laboratory analysis by technique of microscopy on bacterial vaginosis or dysbacteriosis of vagina. Their advantages and restrictions are demonstrated The unified criteria of evaluation are proposed concerning results of microscopy of mucosal discharge of vagina and corresponding classification. Thereafter, three degrees of bacterial vaginosis (dysbacteriosis of vagina) are differentiated: first degree--compensated dysbacteriosis of vagina, second degree--sub compensated dysbacteriosis of vagina and third degree--decompensated dysbacteriosis of vagina. The corresponding laboratory report of physician is formulated. The proposals are presented concerning development of common unified requirements to stages (pre-analytical, analytical, post-analytical) of laboratory diagnostic of bacterial vaginosis (dysbacteriosis of vagina) with purpose of their unambiguous understanding by clinicians and hence their decision making concerning necessity and tactics of management of patient.

[THE COMPARATIVE ANALYSIS OF INFORMATION VALUE OF MAIN CLINICAL CRITERIA USED TO DIAGNOSE OF BACTERIAL VAGINOSIS].

The bacterial vaginosis is one of the most frequent causes of women visiting gynecologist. The diagnostics of bacterial vaginosis is predominantly based on Amsel criteria (1983). Nowadays, the objectivity of these criteria is disputed more often. The analysis of excretion of mucous membranes of posterolateral fornix of vagina was applied to 640 women with clinical diagnosis bacterial vaginosis. The application of light microscopy to mounts of excretion confirmed in laboratory way the diagnosis of bacterial vaginosis in 100 (15.63%) women. The complaints of burning and unpleasant smell and the Amsel criterion of detection of "key cells" against the background of pH > 4.5 were established as statistically significant for bacterial vaginosis. According study data, the occurrence of excretions has no statistical reliable obligation for differentiation of bacterial vaginosis form other inflammatory pathological conditions of female reproductive sphere. At the same time, detection of "key cells" in mount reliably correlated with bacterial vaginosis.

[Effect of the heart electric stimulation on repolarization of fish and amphibian ventricular myocardium].

By the method of synchronous multielectrode cartography (24-unipolar leads), distribution of durations and time of end of repolarization were studied on ventricular epicardium of pikes (Esox lucius) and frogs (Rana esculenta) and in ventricular intramural layers of toads (Bufo bufo) at the ectopic heart excitation. The time of arrival of the excitation wave and of the end of repolarization in each lead was determined from the minimum of time derivative of potential at the period of the QRS complex and by minimum of the T wave, respectively. It has been established that at the ventricle electrostimulation, alongside with deceleration and a change of sequence of the myocardium activation, there occurs redistribution of local repolarization durations: in areas of late activation the repolarization being longer than in zones of early activation (p < 0.05). At stimulation, the apicobasal gradient of repolarization is predominantly changed due to electrophysiological processes in the apical areas. In all studied species. at ectopical excitation of the heart ventricle the sequence of its repolarization repeats the depolarization sequence due to delay of activation (in fish) and redistribution of repolarization durations (in amphibians).

[Repolarization pattern of the ventricular myocardium in pikes].

The study aimed at investigation into the repolarization pattern in the myocardium of fish. Activation times, activation-recovery intervals and repolarization times were determined in the intramural layers of the heart ventricle in eight pikes with multiple plunge electrodes. In the heart ventricle of the pike, the earliest end of repolarization was found in the subendocardium of the base and the subepicardium of the apex, the areas corresponding to the earliest and latest depolarization, respectively. The latest repolarization was observation on the anterior epicardial surface of the base. Endocardialto-epicardial repolarization sequence at the base corresponded to the activation sequence in this area with the transmural gradient of the end of repolarization times being 54 +/- 23 ms (p < 0.001). The transmural difference in activation-recovery interval durations and end of repolarization times decreased as one moved from the base to apex with the maximal apex-to-base end of repolarization gradient being 133 +/- 98 ms (p < 0.10).

[Effect of ectopic excitation on pump function of the hen and dog right heart ventricle].

The pump function of the right heart ventricle has been studied in anesthetized dogs and hens at sinus rhythm, supraventricular rhythm, and subepicardial ectopic excitation of base and apex of the right and left ventricles. Dynamics of the ventricle intracavital pressure was recorded by transmural catheterization. The pump function of the right ventricle in hen (as compared with sinus rhythm) retained to the greater degree at stimulation of the left ventricle apex and deteriorated significantly at stimulation of the right ventricle, whereas in dog (as compared with supraventricular rhythm) it retained to the greater degree at stimulation of the left ventricle base and deteriorated at stimulation of the right ventricle apex. Changes of the pump function of the right heart ventricle at ectopic ventricle stimulation are similar in birds and mammals. Differences in changes of dog and hen pump functions under effect of location of the ectopic excitation seem to be due to morphofunctional peculiarities of heart ventricles.

[Repolarization of canine ventricular myocardium under the supraventricular rhythm].

The ventricular myocardium is characterized by heterogeneity of activation-recovery interval durations. The transmural ARI gradients are present in the right ventricular apex (ARIs monotonically decreased as one moved from the endocardium to the epicardium), and in the left ventricular base (repolarization in the subepicardial layers was significantly shorter than that in the midmyo cardial layers whereas subendocardial ARIs did not differ from the others). The repolarization pattern of these myocardial regions is governed by the distribution of ARIs. In the apical left ventricular and basal right ventricular areas, no significant transmural differences in the repolarization durations were found. The repolarization pattern of these myocardial regions is governed by the activation sequence. In the right ventricle, ARIs were significantly longer at the base and shorter at the apex. In contrast, in the left ventricle, the apical ARIs were prolonged whereas the basal ARIs were abbreviated. The apex-to-base sequence of myocardial repolarization seems to depend on apex-to-base gradient of activation-recovery intervals durations.