Composites Composed of Hydrophilic and Hydrophobic Polymers, and Hydroxyapatite Nanoparticles: Synthesis, Characterization, and Study of Their Biocompatible Properties.

The creation of artificial biocomposites consisting of biocompatible materials in combination with bioactive molecules is one of the main tasks of tissue engineering. The development of new materials, which are biocompatible, functional, and also biodegradable in vivo, is a specific problem. Two types of products can be formed from these materials in the processes of biodegradation. The first types of substances are natural for a living organism and are included in the metabolism of cells, for example, sugars, lactic, glycolic, and ß-hydroxybutyric acids. Substances that are not metabolized by cells represent the other type. In the latter case, such products should not be toxic, and their concentration when entering the bloodstream should not exceed the established maximum permissible level. The composite materials based on a mixture of biodegradable synthetic and natural polymers with the addition of hydroxyapatite nanoparticles, which acts as a stabilizer of the dispersed system during production of the composite, and which is a biologically active component of the resulting matrix, were obtained and studied. The indirect effect of the shape, size, and surface charge of hydroxyapatite nanoparticles on the structure and porosity of the formed matrix was shown. An in vivo study showed the absence of acute toxicity of the developed composites.

Telemedicine platform COVIDREHAB for remote rehabilitation of patients after COVID-19.

The world's practice has shown the importance of medical rehabilitation, which allows increasing the effectiveness of treatment of patients with COVID-19, and also significantly reduce the risks of developing complications after COVID-19. Moreover, timely medical rehabilitation reduces the frequency of disability retirement. We developed and investigated the effectiveness of the telemedicine platform "COVIDREHAB" in order to enhance the effectiveness of the recovery period during self-isolation, as well as to provide access to rehabilitation for patients residing in remote areas or unable to undergo in-person medical rehabilitation. This pilot open clinical study includes 178 patients (108 women and 70 men) aged 32 to 82 years [mean age 50 (33-56) years] who had a moderate disease of COVID-19. We used the specialised platform COVIDREHAB for remote monitoring of the rehabilitation efficiency of patients who suffered from COVID-19. During the study, the supervising doctor assigned the patient a set of specialised questionnaires, which were filled in online. The questionnaires distributed to the patient included questions specifically designed for the COVIDREHAB remote platform as well as the mMRC (Modified Medical Research Council) questionnaire. Patients who completed the remote rehabilitation programme were found to have positive dynamics of indicators of the respiratory system functional state, and complaints.Pulmonary rehabilitation is an important part of case management for patients with respiratory diseases and plays an active role in improving lung function and general well-being of patients. Patients who completed the comprehensive medical rehabilitation program using the information and analytical system COVIDREHAB, were found to have positive dynamics of indicators of the respiratory system functional state, and complaints. Hence, at the end of the course the shortness of breath severity decreased (from 34.8% to 12.4%, as well as the feeling of lack of oxygen from 32% to 17.4%, p <0.05). We anticipate the online approach to rehabilitation will improve the functioning of the respiratory and cardiovascular systems, restore physical function, reduce anxiety and depression, and restore quality of life. An essential benefit of this program is the prevention of secondary complications and reduction of serious adverse effects of COVID-19 treatment."

The CD44high Subpopulation of Multifraction Irradiation-Surviving NSCLC Cells Exhibits Partial EMT-Program Activation and DNA Damage Response Depending on Their p53 Status.

Ionizing radiation (IR) is used for patients diagnosed with unresectable non-small cell lung cancer (NSCLC). However, radiotherapy remains largely palliative due to the survival of specific cell subpopulations. In the present study, the sublines of NSCLC cells, A549IR (p53wt) and H1299IR (p53null) survived multifraction X-ray radiation exposure (MFR) at a total dose of 60 Gy were investigated three weeks after the MFR course. We compared radiosensitivity (colony formation), expression of epithelial-mesenchymal transition (EMT) markers, migration activity, autophagy, and HR-dependent DNA double-strand break (DSB) repair in the bulk and entire CD44high/CD166high CSC-like populations of both parental and MFR survived NSCLC cells. We demonstrated that the p53 status affected: the pattern of expression of N-cadherin, E-cadherin, Vimentin, witnessing the appearance of EMT-like phenotype of MFR-surviving sublines; 1D confined migratory behavior (wound healing); the capability of an irradiated cell to continue to divide and form a colony of NSCLC cells before and after MFR; influencing the CD44/CD166 expression level in MFR-surviving NSCLC cells after additional single irradiation. Our data further emphasize the impact of p53 status on the decay of γH2AX foci and the associated efficacy of the DSB repair in NSCLC cells survived after MFR. We revealed that Rad51 protein might play a principal role in MFR-surviving of p53 null NSCLC cells promoting DNA DSB repair by homologous recombination (HR) pathway. The proportion of Rad51 + cells elevated in CD44high/CD166high population in MFR-surviving p53wt and p53null sublines and their parental cells. The p53wt ensures DNA-PK-mediated DSB repair for both parental and MFR-surviving cells irrespectively of a subsequent additional single irradiation. Whereas in the absence of p53, a dose-dependent increase of DNA-PK-mediated non-homologous end joining (NHEJ) occurred as an early post-irradiation response is more intensive in the CSC-like population MFR-surviving H1299IR, compared to their parental H1299 cells. Our study strictly observed a significantly higher content of LC3 + cells in the CD44high/CD166high populations of p53wt MFR-surviving cells, which enriched the CSC-like cells in contrast to their p53null counterparts. The additional 2 Gy and 5 Gy X-ray exposure leads to the dose-dependent increase in the proportion of LC3 + cells in CD44high/CD166high population of both parental p53wt and p53null, but not MFR-surviving NSCLC sublines. Our data indicated that autophagy is not necessarily associated with CSC-like cells' radiosensitivity, emphasizing that careful assessment of other milestone processes (such as senescence and autophagy-p53-Zeb1 axis) of primary radiation responses may provide new potential targets modulated for therapeutic benefit through radiosensitizing cancer cells while rescuing normal tissue. Our findings also shed light on the intricate crosstalk between autophagy and the p53-related EMT, by which MFR-surviving cells might obtain an invasive phenotype and metastatic potential.

Development of nanostructured bioplastic material for wound healing.

The development of new biomaterials whose characteristics are as close as possible to the properties of living human tissues is one of the most promising areas of regenerative medicine. This work aimed at creating a bioplastic material based on collagen, elastin and hyaluronic acid and studying its structure and properties to assess the prospects for further use in clinical practice. Bioplastic material was obtained by mixing collagen, hyaluronic acid and elastin in predetermined proportions with distilled water. We treated the material with photochemical crosslinking to stabilize biofilm in a liquid medium and form a nanostructured scaffold. A commercial human skin fibroblast cell culture was used to assess the biomaterial cytotoxicity and biocompatibility. The visualization and studies of the biomaterial structure were performed using light and scanning electron microscopy. It has been shown that the obtained biomaterial is characterized by high resilience; it has also a high porosity. The co-culturing of the bioplastic material and human fibroblasts did not reveal any of its cytotoxic effects on cells in culture. It was shown that the biomaterial samples could maintain physical properties in the culture medium for more than 10 days, while the destruction of the matrix was observed 3-4 weeks after the beginning of incubation. Thus, the created biomaterial can be used on damaged skin areas due to its physical properties and structure. The use of the developed biomaterial provides effective conditions for good cell proliferation, which allows us to consider it as a promising wound cover for use in clinical practice.

Prospects of plasmapheresis for patients with severe COVID-19.

On February 11, 2020, the World Health Organization officially named the infection caused by the new coronavirus "Coronavirus disease 2019" (COVID-19). On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) officially named the infectious matter "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). Emergence of severe complications with new coronavirus disease is due to the development of hypercytokinaemia, also known as "cytokine storm". These complications comprise acute respiratory distress syndrome (ARDS), respiratory failure and death. Emerging data point to the logic of using extracorporeal haemocorrection to normalise cytokine levels and reduce the severity of organ disorders. The analysis of the literature indicates that to date, a certain positive experience has been accumulated in the world in the application of extracorporeal methods in clinical practice in patients with COVID-19.

Spontaneous γH2AX foci in human dermal fibroblasts in relation to proliferation activity and aging.

We assessed the effects of donor age on clonogenicity, proliferative potential, and spontaneous γH2AX foci in the proliferating (Ki67 +) and senescent (SA ß-gal +) cultures of skin fibroblasts isolated from 34 donors of different age (23-82 years). Here, we demonstrated that neither the colony forming effectiveness of proliferating (Ki67+) fraction of the fibroblasts nor the average number of γH2AX foci of the same fraction does not depend on the age of the donor. The correlation between the number of γH2AX foci and the donor's age was reliable in quiescent (Ki67-) cells. The average number of γH2AX foci in quiescent fibroblasts of donors older than 68 years was about two times higher than in the same cells of up to 30 years old donors. The number of γH2AX foci demonstrated a statistically significant positive correlation with the fraction of proliferating cells in fibroblast cultures. On average, proliferating cells have twice as many the γH2AX foci in comparison with the quiescent cells. Within a population of proliferating (Ki67+) cells, the degree of senescence correlated with a relative declining of constitutive γH2AX foci number, whereas in the population of quiescent (Ki67-) cells, it was proportional to augmenting the number of the γH2AX foci. Our data on a statistically significant (p=0.001) correlation between the age of the donor and the number of constitutive γH2AX foci in quiescent cells, could point out the ongoing DNA-damage response due in the maintenance of the senescent state of cells.