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The modern complex of regenerative technologies in the treatment of patients with intraarticular osteochondral defects includes surgical methods in combination with the use of cellular and tissue technologies, which promotes acceleration of poliferation and differentiation of cells, activation of their metabolism, creation of conditions for the restoration of blood supply in adjacent bone tissue and optimization of functional conditions of the newly formed regenerate. However, the insufficient evidence base on the impact of these treatments (transplantation of PRP, platelet rich plasma and BMDC, bone marrow-derived cell) leads to conflicting views on their use, as well as numerous discussions about treatment outcomes using these treatments. Purpose of the study. According to the morphological study in an experiment in laboratory animals to evaluate the effectiveness of the use of PRP and BMDCT in the treatment of intra-articular osteochondral injuries. Object and methods. Experimental studies were performed on 32 rabbits. An osteochondral defect in the medial part of the femur of a critical size with a diameter of 3 mm in a depth of 5 mm was reproduced by the dental boron. The defect was not filled (1st series), filled with collagen-fibrin matrix (2nd series), collagen-fibrin matrix with PRP (3rd series) or with BMDCT (4th series). Animals were killed at 40 days. After histological procedures the material was examined under a microscope Olympus ÂÕ 63 and Micros. Morphometric analysis was performed to determine the nature and structure of the regenerate, its integration with surrounding tissues, the evaluation of the content of cell structures and non-cellular elements that were formed in the defect in different series of the experiment using scale recommended by the Committee of the International Cartilage Regeneration Union (SCRS) with our modifications. Research results and discussion. An analysis of the results of the study using a modified histological evaluation scale showed that hyaline cartilage was present only in the regenerate of experimental animals of series No. 3 and No. 4, they did not show significant stratification of the surface of the cartilage. In the experimental group of animals of the series No. 3 receiving PRP, the formation of hyaline cartilaginous tissue with chondroblast, chondrocytes and fibrochondrocytes, which densely filled the bone and cartilage defect, was recorded in the area of the bone and cartilage defect. In the experimental group of animals No. 4, where mesenchymal stem cells of the bone marrow punctate were used, defects located in the articular cartilage were filled with a dense, well developed hyaline cartilaginous tissue with a high degree of its integration with the edges of the defect. The bony trabeculae of the spongiform bone adjacent to the cartilaginous defect formed a network. The comparison of the components of regenerate the morphometric scale in the control and experimental groups was performed and a significant difference was found for all the parameters in the PRP and BMDCT groups compared with the control animals. A statistical difference between PRP and BMDCT was found for the indicator of tissue regenerate and cellular composition, with the use of BMDCT, these indicators prevailed by 1.4 times. Compared with the regeneration indices between the series No. 1 and the series No. 2, statistically significant differences were noted connection of the regenerate with the edges of the articular cartilage defect, elevated in the series No. 2. Conclusion. In this case, the technique involving the use of bone marrow mesenchymal stem cells (BMDCT) was significantly more effective than using PRP

Contact interactions between different cell types play a number of important roles in development, for example in cell sorting, tissue organization, and ordered migration of cells. The nature of such heterocellular interactions, in contrast to interactions between cells of the same type, remains largely unknown. In this report, we present experimental data examining the dynamics of heterocellular interactions between epitheliocytes and fibroblasts, which express different cadherin cell adhesion molecules and possess different actin cytoskeletal organizations. Our analysis revealed two striking features of heterocellular contact. First, the active free edge of an epitheliocyte reorganizes its actin cytoskeleton after making contact with a fibroblast. Upon contact with the leading edge of a fibroblast, epitheliocytes disassemble their marginal bundle of actin filaments and reassemble actin filaments into a geometric organization more typical of a fibroblast lamella. Second, epitheliocytes and fibroblasts form cell-cell adhesion structures that have an irregular organization and are associated with components of cell adhesion complexes. The structural organization of these adhesions is more closely related to the type of contacts formed between fibroblasts rather than to those between epitheliocytes. Heterotypic epithelio-fibroblastic contacts, like homotypic contacts between fibroblasts, are transient and do not lead to formation of stable contact interactions. We suggest that heterocellular contact interactions in culture may be regarded as models of how tissue systems consisting of epithelia and mesenchyme interact and become organized in vivo.

The article presents the program shell developed by the authors to estimate the knowledge of civil servants regarding anti-corruption issues. This development is a part of an information and analysis system, which is aimed not only at automating the analysis of data on knowledge control but it also includes both educational functions and possibilities for automation of the activity of the personnel divisions on the prevention of corruption offenses, formation of maps of corruption risks, observation, study and forecast of deviant corruption-related changes in the conduct of civil servants, assignment of testing, organization of training, etc. Due to the introduction of this program, the personnel divisions will obtain both systemic organization of awareness-raising measures (lectures, seminars) involving servants and the possibility to estimate their psychological condition and the general base of knowledge regarding prohibitions and restrictions in the civil service, practical and theoretical nuances of providing data about income, expenses, assets, liabilities, etc. The authors consider the issues of the introduction of the programs in the state authorities of both federal and regional levels. They point out the need to take into account the peculiarities of the targeted information system of the organization : the compatibility of the development being introduced with the current version of the operating system, as well as the security policy of the targeted system. The study presents the first results of the testing of the software product and includes an assessment of their main factors.

We consider the factor structure prenosological body state of pupils. The experiment involved 43 schoolchildren. Discovered contribution of different components, which determine the functional reserves of the body of schoolchildren. Discovered the most important components of the factor structure prenosological status: anthropometry, cardiorespiratory and physiological components. Set priorities for the factors that should determine the direction of health and fitness classes in the process of correction prenosological states of the organism. It is noted that the greatest influence in the structure of state students have prenosological reserves of the cardiovascular system (37.7%).

The necessity of determining the biological age (BA) in elementary school-age children as an important criterion for prenozological diagnostics is justified from the theoretical as well as practical prospective. The classification of prenozological states based on the BA is presented. The experiment features data of 159 children aged 7-10 years. Analyses of the obtained mean functional age (FA) data shows deviation from the calendar age (CA) in all age and gender groups which enables to diagnose prenozological state of elementary school-age children.

Abstract Background Germline mutations in LKB1 result in Peutz-Jeghers Syndrome characterized by intestinal hamartomas and increased incidence of epithelial cancers. LKB1 encodes a serine/threonine kinase that plays an important role in regulating energy metabolism through the AMPK/mTOR signaling pathway. In addition, LKB1 is homologous to PAR-4, a polarity protein first described in C. elegans, while activation of LKB1 in mammalian epithelial cells induces the polarized assembly of actin filaments. Results To explore the mechanism by which LKB1 interacts with the actin cytoskeleton, we introduced LKB1 into HeLa cells that lack endogenous LKB1. This results in activation of the small GTPase Rho and the assembly of linear actin filaments associated with focal adhesions. These effects on the actin cytoskeleton are attenuated by siRNA-mediated depletion of the guanine nucleotide exchange factor Dbl. Co-expression of the LKB1 with the adaptor protein STRAD induces actin filament puncta associated with phospho-ezrin. Conclusions This study reveals that LKB1 regulates the actin cytoskeleton through a Dbl/Rho pathway.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Pathogen infection and tissue injury are universal insults that disrupt homeostasis. Innate immunity senses microbial infections and induces cytokines/chemokines to activate resistance mechanisms. Here, we show that, in contrast to most pathogen-induced cytokines, interleukin-24 (IL-24) is predominately induced by barrier epithelial progenitors after tissue injury and is independent of microbiome or adaptive immunity. Moreover, Il24 ablation in mice impedes not only epidermal proliferation and re-epithelialization but also capillary and fibroblast regeneration within the dermal wound bed. Conversely, ectopic IL-24 induction in the homeostatic epidermis triggers global epithelial-mesenchymal tissue repair responses. Mechanistically, Il24 expression depends upon both epithelial IL24-receptor/STAT3 signaling and hypoxia-stabilized HIF1α, which converge following injury to trigger autocrine and paracrine signaling involving IL-24-mediated receptor signaling and metabolic regulation. Thus, parallel to innate immune sensing of pathogens to resolve infections, epithelial stem cells sense injury signals to orchestrate IL-24-mediated tissue repair., Competing Interests: Declaration of interests S.L. is now an Asst. Prof. in Pharmacology at UT Southwestern Medical Center; X.C. is now an Asst. Prof. in Radiation Oncology at UT Southwestern Medical Center; K.A.U.G. is currently at Novo Nordisk, Research Center, Oxford, England; C.J.C. is now a postdoctoral fellow at NYU; T.T. is now a graduate student at Yale Univ.; B.H. is now a medical student at Weill Cornell Medical College; S.G.-C. is now an Asst. Prof. in Stem Cells and Regenerative Medicine at UCSD; M.S. is now an embryologist at Tennessee Reproductive Medicine in Chattanooga, TN; J.L. is currently at Temple Univ. C.B.T is a founder of Agios Pharmaceuticals. He is on the board of directors of Regeneron and Charles River Laboratories. E.F. is a member of the editorial board of Cell. She is also a former member of the scientific advisory boards of L’Oréal and Arsenal Biosciences and owns stock futures with Arsenal Biosciences., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim: Improving efficiency of the tibia proximal epimetaphysis fractures treatment by introducing minimally invasive techniques using the up-to-date metallic constructions., Patients and Methods: Materials and methods: The study is based on the results of examination and treatment of 119 patients, using arthroscopic technique. The results were evaluated regarding the P. Rasmussen scheme, post-traumatic arthrosis -Kellgren - Lawrence, life quality - «SF-36 Health Status Survey»., Results: Results: The offered treatment method provided for the following: good outcomes in BI- 94.1%, satisfactory ones - 5.9%; respectively in BII - 91.7%, 8.3%; ВIII - 92.9%, 7.1%; СI- 87.5%,12.5%; СII - 91.7%, 8.3%; СIII -88.9%, 7.4%, unsatisfactory outcomes - 3.7., Conclusion: Conclusions: The tibia proximal epimetaphysis fractures make up from 8.9% to 11% of all lower leg fractures and up to 87% of the knee joint fractures. Such fractures are accompanied with the knee joint soft tissue injuries in up to 56% of cases. The meniscus injury is diagnosed in 50-94% of the patients; collateral ligament injury: 20% - 83%; anterior cruciate ligament injury : 20% - 69%, femoral muscle ligament injury- up to 47%, joint capsule ruptures - up to 75%, fibular nerve injury - 3% of cases. The treatment fails in 24.2-50% of cases. Operative treatment of such injuries using arthroscopic method provides for mini-invasive intervention character, visualizing and splint reposition control; the opposite compression screw provides for strong fixation.

Objective: The aim: To determine the anatomical and biomechanical significance of the static stabilizers of the acromioclavicular joint by conducting numerical modeling using the finite element method and experimental investigation., Patients and Methods: Materials and methods: To ensure the study, modeling of the deformation processes of the clavicle and scapula systems with various combinations of ligament damage was conducted. The COMPAS-3D software package was used to build the simulation model, which allowed obtaining models that are closest to reality. To verify the results of the numerical modeling, corresponding studies of the mechanical characteristics and determination of the stiffness of the investigated systems were carried out using the upgraded TIRAtest-2151 testing stand., Results: Results: The stiffest system is the system in which all ligaments are intact, and the sequence of decreasing stiffness of the system is presented in the following order: damage to lig. trapezoideum; lig. conoideum; lig. claviculo-acoacromiale inferior; lig. claviculo-acoacromiale superior; the coracoclavicular ligament complex; the acromioclavicular ligament complex., Conclusion: Conclusions: Static stabilizers in general, and their components in particular, are characterized by significant anatomical and functional features. The natural stabilization of the acromioclavicular joint is provided by their synergistic interaction, which is the basis for the development and implementation of surgical interventions, the scope of which includes the restoration of both ligament complexes. The loss of stiffness in the «clavicle-scapula» system is significantly more pronounced when lig. acromioclaviculare superior and inferior are damaged (8.5 N/mm) than when lig. conoideum and lig. trapezoideum are damaged (11.6 N/mm).

Nerves are a component of the tumor microenvironment contributing to cancer progression, but the role of cells from nerves in facilitating cancer invasion remains poorly understood. Here we show that Schwann cells (SC) activated by cancer cells collectively function as tumor-activated Schwann cell tracks (TAST) that promote cancer cell migration and invasion. Nonmyelinating SCs form TASTs and have cell gene expression signatures that correlate with diminished survival in patients with pancreatic ductal adenocarcinoma. In TASTs, dynamic SCs form tracks that serve as cancer pathways and apply forces on cancer cells to enhance cancer motility. These SCs are activated by c-Jun, analogous to their reprogramming during nerve repair. This study reveals a mechanism of cancer cell invasion that co-opts a wound repair process and exploits the ability of SCs to collectively organize into tracks. These findings establish a novel paradigm of how cancer cells spread and reveal therapeutic opportunities., Significance: How the tumor microenvironment participates in pancreatic cancer progression is not fully understood. Here, we show that SCs are activated by cancer cells and collectively organize into tracks that dynamically enable cancer invasion in a c-Jun-dependent manner. See related commentary by Amit and Maitra, p. 2240. This article is highlighted in the In This Issue feature, p. 2221., (©2022 The Authors; Published by the American Association for Cancer Research.)

Cellular protrusions generated by the actin cytoskeleton are central to the process of building the body of the embryo. Problems with cellular protrusions underlie human diseases and syndromes, including implantation defects and pregnancy loss, congenital birth defects, and cancer. Cells use protrusive activity together with actin-myosin contractility to create an ordered body shape of the embryo. Here, I review how actin-rich protrusions are used by two major morphological cell types, epithelial and mesenchymal cells, during collective cell migration to sculpt the mouse embryo body. Pre-gastrulation epithelial collective migration of the anterior visceral endoderm is essential for establishing the anterior-posterior body axis. Gastrulation mesenchymal collective migration of the mesoderm wings is crucial for body elongation, and somite and heart formation. Analysis of mouse mutants with disrupted cellular protrusions revealed the key role of protrusions in embryonic morphogenesis and embryo survival. Recent technical approaches have allowed examination of the mechanisms that control cell and tissue movements in vivo in the complex 3D microenvironment of living mouse embryos. Advancing our understanding of protrusion-driven morphogenesis should provide novel insights into human developmental disorders and cancer metastasis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The aim: Improving treatment outcomes in patients with segment tibial bone tissue loss after fractures by improving the ring fixators technology., Patients and Methods: Materials and methods: The study includes the data of 77 patients. The patients were distributed between two groups: the main and control one, using random numbers table. The inclusion criteria were: patients' consent, their age over 18 years, tissue inflammation episodes, fibular defects 4-5cm in size and disseminated scar lesions. RF was applied with the proposed improvements. Finally, a semi-rigid external fusion system Softcast / Scotchcast was used to prevent deformation of the regenerate and create optimal conditions for fusion of fragments., Results: Results: The following results were obtained for the Modified Functional Evaluation System by Karlstrom-Olerud: positive treatment outcomes in the main group made up 97.1%, and 92.9% in the control one. Though, the specific gravity of good and excellent outcomes in the main group was 82.8%, while in the comparison group - just 45.2., Conclusion: Conclusions: Along with considerable positive advantages of the "Ilizarov's" apparatus, some disadvantages have been noted. Elimination of the drawbacks is stipulated for the practical needs, which requires further scientific study.