The annual increase in the number of operations for the curvature of the nasal septum is accompanied by a proportional increase in the number of complications, for example, the development of nasal septum perforation (NSP). The frequency of NSP detection varies from 0.5% to 8%. In 60% of cases, NSP is defined as iatrogenic and is the result of surgical treatment or injury to the nose. In 12-47% of cases, NSP is idiopathic and develops as a result of chronic subatrophic rhinitis, uncontrolled use of intranasal decongestants and topical glucocorticosteroids, and in rare cases it is a manifestation of systemic diseases. The tactics of surgical treatment of NSP is a highly debatable issue. Historically, the treatment of nasal septum defects has evolved from the lengthening of small "whistling" perforations to the development of autoloscutes of the mucous membrane to perform plastic closure of nasal septum perforation. Studies conducted over the past 20 years have shown that the use of displaced vascularized mucosal flaps is the most effective method of surgical treatment of NSP. The effectiveness of this approach over the past 10 years has ranged from 70% to 90%. However, plastic closure of perforation with mucosal flaps is a very complex and labor-intensive process, it is possible provided the surgeon is highly qualified and has extensive experience, and careful care is provided during a long rehabilitation period. Modern research on the treatment and rehabilitation of patients with NSP is aimed at improving the effectiveness of the surgical stage, simplifying the surgical procedure, and shortening the rehabilitation period through the use of transplant materials and cellular technologies. Based on this, the purpose of our work was to analyze domestic and foreign studies on the use of biotechnological approaches in the closure of nasal septum defects.

Various age-related disorders accumulate during aging, causing a decline in tissue and organ function, raising the risk of disease development, and leading to death. Age-related phenotypes are tightly related to an increase in coordinated, progressive changes in the transcriptome, proteome, metabolome, microbiome, and epigenome. Age-dependent modifications of the transcriptome, caused by changes in epigenetic, transcriptional, and post-transcriptional regulation of gene expression, lead to the accumulation of age-related changes in the proteome and metabolome. In turn, dynamic changes in the microbiota during aging also affect gene expression and thus lead to age-related changes in the proteome and metabolome. Recent studies have shown that multi-omic rejuvenation technologies decrease age-related disorders and extend longevity. For example, the short-term induction of the expression of transcription factors that ensure the reprogramming of somatic cells into pluripotent stem cells is accompanied by the restoration of the DNA methylation pattern and transcriptome expression profile characteristic of younger tissues, resulting in an increased lifespan. In this review, we discuss existing multi-omic rejuvenation technologies and the prospects for extending and improving life.

Proteins of the TRIM family are involved in both innate immunity and the nervous system processes and may play an important role in the development of neurodegenerative diseases. In this work, we analyzed the expression of 35 genes of the TRIM family in neural progenitors (NPs), terminally differentiated neurons (TDNs) and glial derivatives (NGs) obtained from induced pluripotent stem cells (iPSCs) of healthy donors (HD) and patients with Parkinson's disease (PD), in the absence of inflammatory stimuli and upon the induction of a nonspecific inflammatory response under the influence of TNFα. In NPs and TDNs of PD patients, compared with HD cells, differences in expression were observed for only a small number of TRIM genes. Under the influence of TNFα in TDNs, the expression of individual TRIM genes was activated, which was more significant in the cells of patients with PD compared to cells of HDs. In NGs of PD patients, the expression of many TRIM genes was initially reduced compared to HD cells and remained low or further decreased after exposure to TNFα. The data obtained demonstrate differences in the network of the TRIM family members in PD neurons and glia compared to control, and also show the multidirectional influence of the inflammatory stimulus on the expression of a number of TRIM genes in these types of cells. Considering the important role of many TRIM genes in the functioning of the innate immune system, it can be assumed that, in PD, more significant disturbances in the functioning of genes of this family occur in glia compared to neurons.

There is no consolidated opinion on the pathogenesis of neurological manifestations of COVID-19, especially after infection. A significant contribution to understanding the mechanisms of neuropathology in COVID-19 can be made by detailed morphologic studies of the brain with assessment of changes in different brain regions during different periods of the infection process.

Cardiac myxoma in its morphology is a typical benign tumor, meanwhile, the fact of its localization in the heart chamber, directly in the constant blood flow, largely determines the clinical behavior of this neoplasm, which is often manifested by the development of characteristics that formally determine the aggressive and even malignant nature of the course. Accordingly, the malignancy of cardiac myxoma is determined more by its clinical behavior (recurrence, multifocality of the lesion, the presence of mechanisms of spread similar to metastasis) rather than by its histological picture. In the structure of primary benign tumors of the heart, myxoma occupies a dominant position and its incidence is up to 85%. According to some authors, the tumor develops from multipotent mesenchymal stem cells of the endocardium, mainly in the area of the fossa ovale, while according to others the histogenesis of the tumor remains unclear. The obligate morphology element is the myxoma cell. The presence of so-called "ring" structures is special, regular and highly specific, and Gamna - Gandy bodies, foci of calcification and superficial thrombosis are considered characteristic secondary destructive morphological signs. The review describes the morphology features, specific clinical manifestations, immunohistochemical parameters of cardiac myxoma, and presents information available in the literature on the mechanisms of tumor spread (metastasis).

Glioblastoma (GB) is the most aggressive malignant brain tumor. To date, there is no optimal treatment approach for this disease. Antidepressants with antitumor effects are one of the new therapeutic directions. A distinctive feature of these drugs is their approval for clinical practice in the treatment of depressive disorders.

An overview of various cell engineering techniques being developed for modern conservative and reconstructive periodontology is presented. The accelerated development of cellular engineering technologies poses to medicine and, in particular, periodontics, the task of early implementation of the results of such experiments into patient management protocols. The main groups of promising techniques that are closest to practical healthcare are: isolation and use of stem cells; synthesis of biologically active (inductive) signaling molecules; development of scaffolds that ensure three-dimensional tissue growth.

Lung cancer occupies a leading position in the structure of global cancer morbidity and mortality, due to the biological properties of the key pool of tumor cells - cancer stem cells (CSCs). The effects of SARS-CoV2 on tumor CSCs and its niche have not been studied.

The number of patients with diabetes mellitus (DM) has been progressively increasing worldwide over the past decades, and many international organizations consider DM as a public health emergency of the 21st century.Critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease (PAD) in DM and is characterized by a high risk of limb loss without revascularization. Traditional treatment tactics include open and endovascular revascularization surgical techniques. However, in patients not eligible for revascularization and in cases where performed surgical treatment performed has been ineffective, there are almost no therapeutic alternatives, often leading to amputations and death. As of today, one of the newest non-surgical treatment options is cell therapy. Among different cells, mesenchymal stromal cells (MSCs) are potentially one of the most prospective for use in this patient population.This article provides an overview of clinical trials using cell therapy in patients with CLI.To analyze publications, electronic databases PubMed, SCOPUS, ClinicalTrials, and ScienceDirect were searched to identify published data from clinical trials, research studies, and review articles on cell therapy for critical lower extremity ischemia. After the search, 489 results were received.As a result of systematic selection, 22 clinical trials were analyzed.According to the analyzed literature data, the use of cell products in this category of patients is effective and safe. Cell therapy can stimulate the formation of new vessels and enhances collateral circulation; it is also reported improved distal perfusion, increased pain-free walking distance, decreased amputation rates, and increased survival rates.Nevertheless, further study of the potential use of this category of drugs is needed.

The number of somatic mutations among all tissues increases along with age. This process was well-studied in hematopoietic stem cells (HSCs). Some mutations lead to a proliferative advantage and expansion of HSCs to form a dominant clone. Clonal hematopoiesis is general in the elderly population. Clonal hematopoiesis of indeterminate potential (CHIP) is a more common phenomenon in the elderly and is defined as somatic mutations in clonal blood cells without any other hematological malignancies. The development of CHIP is an independent risk factor for hematological malignancies, cardiovascular diseases, and reduced overall survival. CHIP is frequently associated with mutations in DNMT3A and TET2 genes involved in DNA methylation. The epigenetic human body clocks have been developed based on the age-related changes in methylation, making it possible to detect epigenetic aging. The combination of epigenetic aging and CHUP is associated with adverse health outcomes. Further research will reveal the significance of clonal hematopoiesis and CHIP in aging, acquiring various diseases, and determining the feasibility of influencing the mutagenic potential of clones.

Mutations in the human PCDH19 gene lead to epileptic encephalopathy of early childhood. It is characterized by the early onset of serial seizures, cognitive impairment and behavioral disorders (including autistic personality traits). In most cases, difficulties arise in selecting therapy due to pharmacoresistance. The pathogenesis of the disease is complex. The data available to us at the moment from numerous studies present the pathogenesis of «PCDH19 syndrome» as multi-level, affecting both the epigenetic support of cell life, and development of stem cells and progenitor cells in the process of neuroontogenesis, and the influence on the neurotransmitter mechanisms of the brain, and disruption of the formation of neural networks with an inevitable increase in the excitability of the cerebral cortex as a whole, and local changes in the highly labile regulatory structures of the hippocampal region. And it is not surprising that all these changes entail not only (and perhaps not so much) epileptization, but a profound disruption of the regulation of brain activity, accompanied by autism spectrum disorders, more profound disorders in the form of schizophrenia or cyclothymia, and the formation of delayed psychomotor development. A «side branch» of these pathogenetic processes can also be considered the participation of PCDH19 dysfunctions in certain variants of oncogenesis. The need for polypharmacy (in most cases) confirms the diversity of mechanisms involved in the pathogenesis of the disease and makes the prospects for the development of effective and rational treatment regimens very vague. Cautious optimism is caused only by attempts at relatively specific treatment with ganaxolone.

Murine gammaherpesvirus 68 (MHV68) establishes latency mainly in B cells and causes lymphomas reminiscent of human gammaherpesvirus diseases in laboratory mice. To study the molecular mechanism of virus infection and how the viral determinants control cell and eventually cause tumorigenesis, readily available latently infected cell lines are essential. For in vitro MHV68 latency studies, only two cell culture systems have been available. Gammaherpesviruses are known to infect developing B cells and macrophages, therefore we aimed to expand the MHV68 latently infected cell line repertoire. Here, several latently infected immature B cell and macrophage-like cell line clones were generated. Hygromycin-resistant recombinant MHV68 was isolated from a laboratory-made latent cell line, HE2.1, and propagated to develop stable cell lines that carry the viral genome under hygromycin selection. Subclones of these cells lines were analyzed for viral miRNA expression by TaqMan qPCR and assessed for expression of a lytic viral transcript M3. The cell lines maintain the viral genome as an episome shown by the digestion-circularization PCR assay. Latently infected cell lines generated here do not express viral miRNAs higher than the parental cell line. However, these cell lines may provide an alternative tool to study latency mechanisms and miRNA target identification studies.

Nasal septal perforation (NSP) is a complex problem in otorhinolaryngology, which leads to impaired nasal breathing and dryness in the nose. This reduces the patient's quality of life and leads to psychological discomfort. The treatment of nasal septum perforation is selected taking into account the clinical manifestations, perforation parameters and general condition of the patient. Currently, a large number of different surgical methods have been described in order to closing the defect of nasal septum. To date, there is no universally accepted method for closing NSP, which stimulates the search and development of new treatment options.

The lacrimal gland (LG) is a tubuloacinar exocrine gland composed of acinar, ductal, and myoepithelial cells. Three-dimensional distribution of acinar lobules, ducts, and myoepithelial cells is necessary for the effective functioning of the organ. LG is the main organ of immune surveillance of the ocular surface system. The embryogenesis of the gland is regulated by the interaction of genetic mechanisms, internal epigenetic (enzyme systems, hormones) and exogenous factors. There is no doubt that there is a clear genetic program for the implementation of the complex process of embryonic development. The mechanisms regulating LG organogenesis initiate the work of a huge number of structural oncogenes, transcription and growth factors, etc. Studying the expression and selective activity of regulatory genes during organ development, their participation in the differentiation of different cell types is a current trend at the nexus of clinical genetics, molecular biology, embryology and immunocytochemistry. Due to its relatively simple structure and accessibility, human LG is a suitable object for potential application in regenerative medicine. Development of a universal protocol for obtaining functional differentiated secretory epithelium of LG capable of expressing tissue-specific markers is an urgent task. Determining the nature and origin of stem cells and progenitor cells will allow the isolation and multiplication of these cells in culture. After obtaining a functionally active culture of LG cells, it is possible to create a model of autoimmune diseases.

Limbal stem cell deficiency (LSCD) is one of the leading factors negatively affecting the success of keratoplasty, and its treatment remains an urgent problem in ophthalmology. With the development of regenerative medicine, one of the promising approaches is the transplantation of tissue-engineered constructs from cultured limbal stem cells (LSCs) in biopolymer carriers.

Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.

Lymphoid tumors with testicular involvement in childhood are rare and heterogeneous. The disease may manifest with uni- or bilateral scrotal enlargement. Comprehensive examination includes evaluation of all lymph nodes involvement, as well as ultrasound examination, magnetic resonance imaging and positron emission tomography. A diagnosis is made on basis of morphological and immunohistochemical verification. Determination of lymphoid tumor variant and stage, is recommended to perform chemotherapy according to prognostic risk group, and, in some cases, transplantation of hematopoietic stem cells is required as consolidation therapy. We present three rare clinical cases of follicular lymphoma with testicular involvement, T-lymphoblasti progenitor cell lymphoma, and B-lineage acute lymphoblastic leukemia (ALL) relapse. Different schemes of chemotherapy, combined with orchiectomy (in 2 of 3 cases) resulted in prolonged complete remission. In the first case, due to treatment-refractory B-lineage ALL, the disease was incurable. Our data on clinical, morphological, immunohistochemical and therapeutic features of lymphoid tumors with testicular involvement make it necessary to form multidisciplinary teams, including pediatric urologists, hematologic oncologists and surgeons for timely diagnosis and successful treatment.

Ischemic and hemorrhagic strokes, traumatic brain injury, bacterial and viral encephalitis, toxic and metabolic encephalopathies are very different pathologies. But, they have much more in common than it might seem at first glance. In this review, the authors propose to consider these brain pathologies from the point of view of the unity of their pathogenetic mechanisms and approaches to therapy. Particular attention is paid to promising therapeutic approaches, such as therapy using cells and their secretion products: an analysis of the accumulated experimental data, the advantages and limitations of these approaches in the treatment of brain damage was carried out. The review may be of interest both to specialists in the field of neurology, neurosurgery and neurorehabilitation, and to readers who want to learn more about the progress of regenerative biomedicine in the treatment of brain pathologies.

Theranostics combines diagnostics and therapeutic exposure. Regarding glioblastomas, theranostics solves the problem of detecting and destroying tumor stem cells resistant to irradiation and chemotherapy and causing tumor recurrence. Transmembrane surface antigen CD133 is considered as a potential marker of tumor stem cells.

Targeted delivery of chemotherapeutic agents with aptamers is a very effective method increasing therapeutic index compared to non-targeted drugs.