bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical laws of eukaryotic DNA patchiness
Authors: Kayumov A. R , Saetgaraeva AA. A , Markelov OA. A , Bogachev M. I
Published: October 2024

Active development of the genetic engineering and expression of foreign genes in various organisms revealed the requirement of the DNA sequences adaptation to the genetic machinery of a host cell including adaptation of both functional elements of the genetic code and its tertiary architecture. The annotated genomes of organisms at different evolutionary levels that are widely used as models were obtained from the Genbank (ftp://ftp.ncbi.nlm.nih.gov/genomes). The probability density functions of the sizes of structural elements of the genetic code were assessed and analyzed. The analysis of the distribution of sequences of coding DNA (genes and exons) and noncoding DNA (intergenic sequences and introns) revealed their universal pattern in genomes of all eukaryotes independently of their evolutionary level, the average number of introns in a gene, their sizes and the total genome size. It allows claiming that mechanisms of genomic reorganizations as a result of insertions, deletions, mutagenesis, duplications and others exhibit universal character. The size of inserted/deleted sites of DNA directly depends on the average size of the respective structural elements of a genetic code (genes, introns, exons) of the organism. Therefore the genetic engineering designs where the DNA donor and recipient are located at different evolutionary levels require the structural elements of foreign DNA being adapted to their average sizes of the host to minimize the negative effects from the reorganization of the genetic machinery of the host.
Otsenka sokratitel'noy funktsii diafragmal'noy myshtsy mSOD1 transgennykh myshey s model'yu bokovogo amiotroficheskogo skleroza
Authors: Nurieva L. R , Islamov R. R , Grigor'ev P. N , Rizvanov A. A , Zefirov A. L , Mukhamed'yarov M. A
Published: October 2024

Amyotrophic lateral sclerosis (ALS) - incurable neurodegenerative disease, which is characterized by progressive loss of motoneurons, atrophy and paralysis of skeletal muscles. The main immediate cause of death in ALS patients is a paralysis of the respiratory muscles. In the present study we investigated the contractile characteristics of diaphragm muscle of mSOD1 transgenic mice with ALS model at presymptomatic (3-4 MO) and symptomatic (6-7 MO) stages of the disease. In myographic experiments under electrical stimulation of muscle we showed an increase in force and duration of a single muscle contraction, force of summed muscle contractions (5-50 Hz), diaphragmatic muscle mass at mSOD1 symptomatic mice compared to presymptomatic and wild-type mice. The absence of changes in the contraction threshold and «force-stimulus» curve at symptomatic mSOD1 mice suggests that found differences are not related to changes in the excitability of muscle fibers. Results of the study may be explained in terms of activation of compensatory mechanisms in the «motoneuron - neuromuscular synapse - skeletal muscle» in response to the development of neurodegenerative process. Presented findings extend current understanding of the pathogenesis of amyotrophic lateral sclerosis and can be used to estimate the rate of progression of the disease in mSOD transgenic animals.
Role of potassium channels in the negative inotropic effect of hydrogen sulfide in mouse atrium
Authors: Lifanova A. S , Khaertdinov N. N , Zakharov A. V , Gizzatullin A. R , Sitdikova G. F
Published: October 2024

The effect of sodium hydrosulfide (NaHS) - donor of hydrogen sulfide (H2S) on the force of contraction of isolated mouse atrium was studied. Cumulative application of NaHS in concentrations 100, 200 and 300 ^M induced dose-dependent decrease of the force of contraction, the maximum velocity of contraction and relaxation of the myocardium. A substrate of H2S synthesis - L-cysteine in concentrations 1, 10, 50 uM also had the negative inotropic action, whereas a blocker of H2S synthesis - p-cyano alanine caused an increase of the force of contraction. Inhibition of K-channels by tetraethylammonium (2 mM) caused the increase of the amplitude of contraction and the reduction of negative inotropic effect of NaHS in all used concentrations. After the inhibition of ATP-dependent K-channels by glibenclamide NaHS action was prevented in concentration 100 uM, significantly decreased in concentration 200 uM and didn't changed in concentration 300 uM. Activation of ATP-dependent K-channels by diazoxide did not affect the negative inotropic effect of NaHS. The obtained data suppose that in the mouse atrium exogenous and endogenous H2S causes a reduction of the force of contraction, which is mediated by the activation of ATP-dependent, calcium-activated or voltage-dependent K-channels.
Helicobacter pylori infection in children in Kazan and factors influencing the effectiveness of eradication therapy
Authors: Khalikova A. R , Faizullina R. A , Akhmetov I. I , Ivanovskaya K. A , Abdulkhakov S. R
Published: October 2024

The effectiveness of H. ру/ог/ eradication therapy depends on many factors, including the patients' compliance, H. ру/ог/ sensitivity to antibiotics, the rate of proton pump inhibitors metabolism in the liver. The Aim of this study was to investigate the frequency of mutations underlying the development of H. ру/ог/ resistance to clarithromycin and CYP2C19 genetic polymorphism in children with gastroduodenal pathology. The study included 91 patients with different types of gastroduodenal pathology. H. ру/ог/ was revealed using urease breath test (Helic-test, Russia), polymerase chain reaction (PCR), and cytology. In 26 children in whom the presence of H. ру/ог/ was confirmed by PCR, the presence of mutations (for three sites - A2142G, A2143G, T2717C) in the 23S RNA causing H. ру/ог/ resistance to clarithromycin was analysed. In 80 patients cytochrome P450 2C19 polymorphism was studied as well. H. ру/ог/ was detected by urease breath test in 80 children (87.9%); by PCR - in 54 out of 91 (59.3%). A2143G mutation in the 23S RNA gene was found in 2 out of 26 children (7.7%). A2142G and T2717C mutations were not detected in any case. It was shown that 61 patients out of 80 (76.3%) were CYP2C19*1/*1 genotype carriers; 19 (23.8%) had CYP2C19*1/*2 or CYP2C19*1/*3 genotype. CYP2C19*2/*2, CYP2C19*3/*3 and CYP2C19*2/*3 genotypes weren't found in any patients. The level of H. ру/ог/ clarithromycin resistance in children is 7.7%. The phenotypic group referring to the rapid proton pump inhibitors metabolizers is predominant (76.3%) in children with H. ру/ori-associated gastroduodenal pathology.
Intracellular localization analysis of a conjugate of recombinant histone H1.3 with photoactivated fluorescent dye
Authors: Shaposhnikov M. N , Solovyeva D. O , Zaitsev S. Yu , Solovyeva V. V , Salafutdinov I. I , Rizvanon A. A
Published: October 2024

Histone proteins are promising carriers for delivery of recombinant nucleic acids in various cell cultures. Conjugates of proteins with fluorescent dyes are modern tools in the study of cellular transport and intracellular distribution of important biopolymers. The aim of this work was to optimize the method of recombinant histone H1.3 conjugation with photoactivatable fluorescent dye. Also we studied intracellular penetration and subcellular localization of the resulting conjugate. Resulting conjugate was capable of intensive fluorescence in the red region of the spectrum after irradiation with violet light. The degree of conjugation was determined under different reaction conditions. A comparison of the cytotoxicity of histone H1.3 and its conjugate with photoactivated fluorescent dye in HeLa cells and its intracellular localization was characterized. We found that conjugates mainly localize in recycling endosomes and to a lesser extent in peroxisomes. Thus, the resulting conjugate of recombinant histone H1.3 with photoactivatable fluorescent dye can be used for further studies its anticancer activity and as carrier for drugs and nucleic acids delivery into human and animal cells.
Non-human primate oesophagus decellularization
Authors: Gubareva E. A , Sjoqvist S. , Sotnichenko A. S , Mei Ling Lim , Torres N. F , Danilenko K. A , Orlov S. V , Chvalun S. N , Grigoriev T. E , Krasheninnikov S. N , Porhanov VA. A , Polaykov I. S , Kuevda E. V , Gumenyuk I. S , Macchiarini P.
Published: October 2024

Transplantation is an effective treatment option for patients suffering from different end-stage diseases; however it is associated with a constant shortage of donor organs and lifelong immunosuppressive therapy. Obtainment of tissuengineered scaffolds using decellularization with the following recellularization may become an alternative treatment option due to restoration, replacement and regeneration of damaged cells, tissues and organs. The main objective of this research is obtainment of decellularized esophagus matrices in non-human primate models followed by pathomorphological evaluation. A modified detergent-enzymatic method involving sodium deoxycholate and DNAse was used for esophagus decellularization. The conducted morphological investigation proved preservation of tissue architectonics as well as absence of cells and nuclear material. Evaluation of biomechanical properties of the scaffold revealed similar mechanical strength characteristics in native and decellularized samples; however, rupturing deformation was higher. The obtained results allow continuing research on the possibility of using decellularized esophagus matrix in non-human primate models for recellularization with the following differentiation, revascularization and reinnervation for hetero- and orthotopic transplantations.
Application of stromal vascular fraction cells of adipose tissue for treatment of hyaline cartilage defect of the medial femoral knee condyle: case report
Authors: Masgutov R. F , Salihov R. Z , Rizvanov A. A , Salafutdinov I. I , Bogov A. A , Plaseichuk Yu. A
Published: October 2024

The article presents a case report of successful treatment of the 50 years old female patient with osteoarthritis of the knee with autologous cells stromal vascular fraction (SVF) from adipose tissue. SVF autologous cells were transplanted into the local cartilage defect of the medial femoral condyle composed of fibrin glue. In 5 months after the operation the patient noted pronounced decrease the pain, increase range of motion in the knee joint. According to the MRI the almost complete decrease of subchondral edema, absence of synovitis were observed. The follow-up was 3 years.
The effects of the male sex hormone (testosterone) on the functional activity of T-lymphocytes different degrees of differentiation
Authors: Shupletsova V. V , Khaziakhmatova O. G , Gutsol A. A , Sokhonevich N. A , Yurova K. A , Litvinova L. S
Published: October 2024

The aim of the study was a comprehensive assessment of testosterone effects on the functional activity of T lymphocytes of different differentiation degrees (naive -CD45R + and primed -CD45RO+). Material and methods. CD45RA+ and CD45RO+ T cells obtained from a suspension of mononuclear cells from healthy donors (by immunomagnetic separation) were used as a study material (n = 48). The activation model which reflects the interaction of T lymphocytes of different differentiation degrees with antigen-presenting cells (CD2/CD3/CD28-complex activated T cells) was used to assess dose-dependent effects of testosterone on functional activity of T memory cells of different differentiation degrees. Viability assessment and identification of surface molecules CD25, CD71, CD95 on T cells of different differentiation degrees were performed by flow cytometry; the concentration of IL-2 in supernatant cell cultures was performed by enzyme immunoassay; assessment of the relative mRNA expression level of the telomerase catalytic subunit hTERT gene was performed by polymerase chain reaction. Statistical analysis was made using IBM SPSS Statistics 20 (Statistical Package for the Social Sciences). Results. The proapoptotic effect of testosterone on CD2/ CD3 / CD28-activated primed (CD45RO+) T cells has been established that may be due to nongenomic effects of the male sex hormone. Testosterone-induced changes of the system parameters IL-2/IL-2Ra induced by activated T-cells different degrees of differentiation is unidirectional, have different rates and depend on concentration of the hormone.. Suppressive effects of testosterone largely affect naive (CD45RA+) T cells. Dose-dependent effects of testosterone on the telomerase catalytic subunit (hTERT) gene expression in the background of antigen-independent activation are multidirectional and determined by the degree of T cells differentiation.
Development of implantable cell-tissue-engineering designs of auxiliary liver for the treatment of liver failure
Authors: Onishchenko N. A , Gulay Y. S , Shagidulin M. Y , Nikolskaya A. O , Bashkina L. V
Published: October 2024

The paper analyzes the achievements and prospects of creating implantable cell- and tissue-engineering designs (CEDs and TEDs) of auxiliary liver to treat liver failure. Emphasizes the need to maintenance long-term and steady function of implantable CEDs and TEDs at the treatment of liver failure, by forming in them de novo hepatospecific structures and transformation of these structures in the new centers of restorative regeneration of damaged liver. CEDs and TEDs acquire these properties due to inclusion in their designs small-differentiated cells: liverspecific cells (parenchymal and non-parenchymal), cells, committed in hepatoid direction and bone marrow cells, adherent to the biocompatible and biodegradable 3D-material, simulating the properties of the extracellular matrix The article analyzes the advantages, disadvantages and prospects for using the major groups of matrices materials (biological, synthetic,inclusive biopolymer and tissue-specific composite materials, obtained by liver decellularization). Indicates that the biopolymer materials occupy a preferred place among biodegradable scaffolds as have not only biocompatible, but also the properties of biostimulants. Since the production of the TEDs requires the provision of adequate stereotypical distribution of different types of cells in the matrix is paid great attention to the production of micro-scale, medium-scale and large-scale TEDs of auxiliary liver. However, points out that none of the problems of producing TEDs liver (choice of sources and technologies to produce small-differentiated cells, the selection matrix and technology of cell-sowing, the choice of assembly technology TEDs) can not be considered definitively settled
The role of EF-hand Са2+/Mg2+-binding tescalcin protein in cell proliferation and differentiation
Authors: Kolobynina K. G , Solovyeva V. V , Slepak V. Z , Rizvanov A. A
Published: October 2024

EF-hand Са2+/Мд2+-binding proteins are involved in many important processes in the body. Identification and analysis of the EF-hand motifs in the genome led to the discovery of novel Ca2+-binding proteins, which are potentially useful for biomedical applications. One of such molecules is tescalcin - 24 kDa protein with one EF-hand motif. Tescalcin plays an important role in differentiation of hematopoietic cells by regulating the expression of Ets family transcription factors via PMA-induced ERK-pathway. At the molecular level, it was shown to interact with subunit 4 of signalosome COP9 and Na+/H+-exchanger. Recently a potential use of tescalcin for cancer diagnostics was demonstrated
DNA of ‘minimal’ cells (mycoplasmas) in the metagenomes of Arctic permafrost
Authors: Vishnyakov I. E , Borchsenius S. N , Kayumov A. R , Shmakova L. A , Rivkina E. M
Published: October 2024

During the long geological time enzymes, nucleic acids, viruses and viable microorganisms can be kept in permafrost. It is difficult to get a holistic view of the microbial community of permafrost using only classical microbiological methods. The analysis of metagenomes of permafrost allowed us to identify the genetic material of ancient mycoplasmas - pathogens of humans, animals and plants Sampling, isolation of total DNA from soil, sequencing (Illumina), metagenomic data processing (MG-RAST, M5nr, UniProt, Krona). Mycoplasma species composition in permafrost soil samples of different origin, but of comparable age (31-32 thousand years), was predicted A comparative analysis of short polypeptides encoded by fragments of ancient DNA with corresponding parts of proteins of modern mycoplasmas was done We discuss the phylogenetic history of Mollicutes, the plasticity of mycoplasma genomes, and the pathogenic potential of the permafrost
Apoptosis in regenerative histogenesis of the liver after partial hepatectomy in rats
Authors: Gazizov I. M , Gumerova A. A , Kiassov A. P
Published: October 2024

Study of liver regeneration after partial hepatectomy in last few decades enabled to understand hourly changes of expression of different genes, levels of cytokines, determine proliferation kinetics of liver cell types. Unfortunately, processes of apoptosis, which always activates together with regeneration was not given enough attention. In a practical point of view, understanding of apoptosis is needed for development of new therapeutic approaches in liver treatment based on enhancing of anti-apoptotic signals and inducing cells into proliferation. This work was dedicated to study apoptosis during liver regeneration after partial hepatectomy in rats. We analyzed expression of PCNA, caspase 3 and 9, Bcl-2 immunohistochemically during liver regeneration on 1, 2, 3, 5, 7, 14 postoperative days. Our results have showed that caspase 9 and Bcl2 are expressed during first postoperative week, caspase-3 only in first three days. Maximal expression of caspase 9 in hepatocytes and sinusoidal cells occurs after 2 days, in cholangiocytes - after 5 days. Maximal expression of Bcl-2 in sinusoidal cells occurs after 3 days, in hepatocytes and cholangiocytes - after 5 days. So, during liver regeneration after partial hepatectomy in rats mechanisms of apoptosis and antiapoptosis are activated simultaneously. Irreversible apoptosis is possible only during first 3 postoperative days and involves only minor fraction of hepatocytes and sinusoidal cells
Effect of recombinant plasmid constructs encoding combinations of dog and horse vegf and bmp2 cDNAs on mesenchymal stromal cell differentiation in vitro
Authors: Zhuravleva M. N , Zakirova E. Y , Masgutov R. F , Valiullin V. V , Deev R. V , Rizvanov A. A
Published: October 2024

Gene therapy is one of the most promising fields in modern regenerative medicine, though today there is no approved veterinary gene therapy drugs on the market. We have created species-specific gene-engineering plasmid constructs based on plasmid DNA encoding genes of dog and horse vascular endothelial growth factor and bone morphogenetic protein 2, which can be potentially used in treatment of domestic animals traumas and locomotor system disorders In vitro studies of these constructs have shown their effect on stimulation of osteogenic, chondrogenic differentiation and angiogenesis in mesenchymal stem cells in vitro
Umbilical cord-derived multipotent mesenchymal stromal cells: biological properties and clinical applications
Authors: Arutyunyan I. V , Makarov A. V , Elchaninov A. V , Fatkhudinov T. Kh
Published: October 2024

The article presents the current literature evidence and own data on the origin and properties of human umbilical cord-derived multipotent mesenchymal stromal cells including proliferative potential, plasticity, stability of caryotype and phenotype, and immunomodulatory activity A review of clinical trials using this cell type is performed Prospects for the use of multipotent stromal cells, derived from umbilical cord, in cell transplantation associate with the need for specialized biobanking and transplant standardization criteria
Hepatic stellate cells - regional stem cells of the liver or a component of microenvironment?
Authors: Shafigullina A. K , Gumerova A. A , Kiassov A. P
Published: October 2024

For years, it is debated about the nature and localization of stem cell of the liver. In recent years, a particular interest is paid to hepatic stellate cells According to the conducted researches, these cells are actively involved in restoring of hepatocytes population by different liver damages and they have a number of properties specific to stem cells. It should be noted that hepatic stellate cells are able to maintain viability in culture and differentiate into hepatocyte direction under certain conditions in vitro. Interestingly, hepatic stellate cells may themselves create such conditions for progenitor cells in vivo, as well as in vitro This is achieved thanks to the hepatic stellate cells secretion of the extracellular matrix proteins, a complex of growth factors and establishment of direct intercellular contacts. Stellate cells, localized in perisinusoidal space, are also influenced by the surrounding hepatocytes and endothelial cells Thus, perisinusoidal space is a kind of dynamic system, in which hepatocytes and endothelial cells determine the “resting” state of stellate cells, and the latter, if necessary, can be activated and participate in restoration of the liver cell populations. Based on these data, the researchers suggest that the hepatic perisinusoidal space - a niche of hepatic stellate cells, regional stem cells of the liver
Transplantation of allogeneic mesenchymal stromal cell for treating corneal ulcers in cats
Authors: Zakirova E. Y , Valeeva A. N , Faizullina R. R , Akhmetshin R. F , Nefedovskaya L. V , Rizvanov A. A
Published: October 2024

At present, a great interest for the veterinary practice is the use of stem cells to treat diseases of the eye. This study was conducted to evaluate the therapeutic effect of allogeneic multipotent mesenchymal stromal cells derived from adipose tissue for the treatment of traumatic corneal ulcers in cats Our results indicate that the stem cells stimulate regenerative processes in the damaged cornea
Platelet activation and apoptosis induced by pathogenic immune complexes containing platelet factor 4
Authors: Nevzorova T. A , Mordakhanova E. R , Andrianova I. A , Litvinov R. I
Published: October 2024

A severe complication of heparin therapy is heparin-induced thrombocytopenia, which manifests as thrombophilia, including diffuse microthrombosis One of the main triggers of thrombosis are immune complexes formed by antibodies against platelet factor 4 and heparin , followed by massive activation of platelets probably under the influence of these pathogenic immune complexes The mechanisms of platelet impairment by the antigen-antibody complexes are largely unknown. In this work direct effects of the immune complexes formed by recombinant platelet factor 4 and a pathogenic anti-platelet factor 4 monoclonal antibody on isolated human platelets in vitro were investigated. Morphological and biochemical changes in platelets were studied by scanning electron microscopy and flow cytometry It is shown that the pathogenic immune complexes cause platelet activation including formation of pseudopods and platelet aggregation In addition, an increase of phosphatidylserine exposure on the platelet surface and a decrease in mitochondrial membrane potential were observed accompanied by formation of platelet-derived microparticles bearing phosphatidylserine The results indicate that the platelet factor 4-containing pathogenic immune complexes induce platelet activation and apoptosis, which can be an important part of the pathogenesis of thrombocytopenia and microthrombosis complicating heparin administration
Morphofunctional reaction of T-lymphoblasts of Jurkat line on the titanium oxides coating
Authors: Khlusov I. A , Litvinova L. S , Shupletsova V. V , Sokhonevich N. A , Khaziakhmatova O. G , Khlusova M. Yu , Sharkeev Yu. P , Pichugin V. F
Published: October 2024

Human leukemic T-lymphoblastoid cells (hereinafter Jurkat T-cells) which was applied actively for modeling of T-lymphocytes reaction have been used in vitro We have examined morphofunctional response of Jurkat T-cells to 24-h in vitro contact with titanium substrates (12x12x1 mm3) covered by titanium oxide (TiO, TiO2) bilateral coating that was prepared by microarc method from an aqueous solution of 20 mass % orthophosphoric acid. 27-98% of immortalized cells in control culture (without an addition of the specimens) had CD3+CD4+CD71+CD45RA+ immunophenotype and secreted IL-2, IL-4, IL-8, IL-10 and TNFα, but not IL-1b and IL-6. Other markers of cell activation, differentiation, maturation and death (CD8, CD16, CD56, CD25, CD95) were found at 0 - 2. 5% of the cell population. The addition of bulk specimens with oxide coating reduced statistically CD3, CD4, CD8 и CD95 membrane markers presentation on Jurkat T-cells and decreased IL-4 and TNFα secretion Structural (antigens expression) and functional (cytokines secretion) Jurkat T-cells inactivation was not connected with the generation of intracellular reactive oxygen species (ROS), and was not mediated by TiO2 nanoparticles (diameter of 14±8 nm; doses of 1 mg/L or 10 mg/L) which can be released under samples biodegradation. Spearman's correlation analysis showed the inhibiting action of the oxide surface roughness in the range of Ra = 2,2-3,7 μm on the number of viable Jurkat T-cells (rs = -0. 95; n = 9; p
Modification of polycaprolactone scaffolds with vascular endothelial growth factors for potential application in development of tissue engineered vascular grafts
Authors: Sevostyanova V. V , Golovkin A. S , Antonova L. V , Glushkova T. V , Barbarash O. L , Barbarash L. S
Published: October 2024

In this study, we investigated a biological activity of nonwoven polycaprolactone scaffolds for controlled delivery of vascular endothelial growth factors. The tube scaffolds with incorporated vascular endothelial growth factors were fabricated by method of electrospinning. The polycaprolactone scaffold containing growth factor provided a morphology similar to the native extracellular matrix. The sustained release of biologically active growth factor from scaffold was observed for 80 days The assessment of adhesion and proliferation of multipotent mesenchymal stem cells and endothelial cells on the material surface showed that scaffolds with vascular endothelial growth factors are able to maintain the cellular activity. Results of study demonstrated that incorporated growth factors provide active proliferation of endothelial cells on porous material and cells penetration inside the scaffold. This approach to the creation of a biologically active environment in the scaffold has a great potential in the development of grafts for blood vessels regeneration
Comparative analysis of secretory profile of human mesenchymal stromal cells differentiated in myogenic direction
Authors: Samchuk D. P , Pulin A. A , Eremin I. I , Gilmutdinova I. R , Korsakov I. N , Zorin V. L , Zorina A. I , Grinakovskaya O. S , Lazareva N. L , Eremin P. S , Petrikina A. P , Gomzyakov A. E , Deev R. V , Timashkov D. A , Vit'ko N. K , Kotenko K. V , Kopnin P. B
Published: October 2024

Up to this day there are lots of data accumulated about the role of cytokines in regulation of different tissues homeostasis independently of inflammation framework. Skeletal muscles produce a wide range of biologically active molecules both in a normal condition and after injuries of different etiologies. Moreover, cultures of cells isolated from muscle tissue show same properties. In this regard identification of cytokines profile secreted by cells with myogenic potential is of particular importance as it will help to choose optimal cell types and their sources for clinical application Our research group previously demonstrated the possibility of obtainment of myogenic cells from gingival mucosa derived multipotent mesenchymal stromal cells (MMSC) However, secretory profile of this myogenic cells is not thoroughly investigated to this day The study was conducted on cultures of skin fibroblasts, MMSc derived from the attached and alveolar parts of the gingival mucosa and gingival mucosa MMSc, differentiated in a myogenic direction cells were isolated from skin and gingival mucosa biopsy specimens of 15 healthy volunteers. ELISA assay was performed for evaluation of 48 proinflammatory and anti-inflammatory cytokines, chemokines and growth factors Our data demonstrates tendency of most investigated proteins secretion gradual increase in the following sequence: skin fibroblasts - attached gingival mucosa MMSC - alveolar gingival mucosa MMSC - differentiated myoblasts, including factors directly involved in myogenesis, skeletal muscle homeostasis and regeneration Thus, alveolar gingival mucosa MMSC both before and after induction of myogenic differentiation potentially could facilitate skeletal muscle regeneration Our results indicate that subpopulation of MMSC derived from alveolar gingival mucosa are perspective candidates for clinical usage in patients with skeletal muscle disorders
Development of dispersed cell system of cervical epithelium in human prenatal ontogenesis
Authors: Zheglova M. Y , Danilov R. K
Published: October 2024

A histological characteristic of the epithelial lining of the cervix is the most important criterion for evaluating its reactive changes. The aim of the research is to give the morphofunctional characteristics of the epithelial cells (epitheliocytes) of the cervix in human prenatal ontogenesis. 50 embryos and prefetuses from 4 to 12 weeks of fetal development, and 64 fetuses from 13 to 30 weeks of gestation have been studied Analysis was performed by using the histochemical, morphometric, cytospectrophotometric and statistical methods. Paramesonephric duct development occurs involving the coelomic epithelium, mesonephric duct epithelium and undifferentiated cells in the part of the urogenital blastema. in the late 12th and early 13th week of fetal development there is a particular area where a close interaction of the epithelial lining of the combined paramesonephric and mesonephric ducts and the dorsal wall of the urogenital area is found. The connection of the uterine channel with the external environment is formed from 13th to 20th week of development. invagination of the epithelial lining of the urogenital sinus towards the united paramesonephric ducts and the formation of a genital cord take part in this process. The junction of two kinds of epithelia: the vaginal mucosa and cervical mucosa is formed since 25th weeks of gestation. in the basal part of the cervical epithelium the individual cells are detected. According to the results of the research these cells should be classified as a derivative of the epithelial lining of the urogenital sinus. They retain their determination and due to the character of their localization may be referred to the dispersed cellular system of the mucous membrane of the cervix.
Homing and survivability of genetically modified mononuclear umbilical cord blood cells after transplantation into transgenic G93A mice with amyotrophic lateral sclerosis
Authors: Safiullov Z. Z , Garanina E. E , Izmailov A. A , Garifulin R. R , Fedotova V. Y , Salafutdinov I. I , Rizvanov A. A , Islamov R. R
Published: October 2024

To overcome the effects of neurodegeneration, as an alternative option of pharmacotherapy, the genetically modified human umbilical cord blood mononuclear cells overexpressing vascular endothelial growth factor (VEGF), glial-derived neurotrophic factor (GDNF), neuronal cell adhesion molecule (NCAM) were suggested. The migration potential and survivability of the genetically modified cells based on expression of therapeutic gene in different combinations after transplantation into G93A mice with amyotrophic lateral sclerosis model was studied The pattern of homing and survivability of the genetically modified cells in a spinal chord after different period of time after treatment was shown by immunofluorescent analysis Based on the level of survived cells and the combination of therapeutic genes the life extension of G93A mice was observed.
Direct modification of cells using polycation-stabilized silver nanoparticles
Authors: Tarasova E. Y , Naumenko E. A , Rozhina E. V , Fakhrullin R. F
Published: October 2024

Here we report the surface functionalization of human lung carcinoma cells A549 with polyallylamine hydrochloride-stabilized silver nanoparticles. We investigated the time and dose-dependent effects of AgPAH on cells, the influence of functionalization on the viability of cells, monolayer formation and proliferative activity Safe concentration of silver nanoparticles stabilized with polyallylamine hydrochloride for A549 cells were determined The differential effects of silver nanoparticles stabilized with polyallylamine hydrochloride on cell function and organelles were revealed
Role of K(ATP)-channels in the effects of hydrogen sulfide on the contractility of rat ventricular myocardium
Authors: Khaertdinov N. N , Lifanova A. S , Gizzatullin A. R , Sitdikova G. F
Published: October 2024

The effect of sodium hydrosulfide (NaHS) - donor of hydrogen sulfide (H2S) on the force of contraction of isolated rat ventricle was studied. Application of NaHS in concentrations 1 and 10 μМ resulted in an increase and in concentrations 50, 100, 200 and 300 μМ - dose-dependent decrease of the force of contraction. Inhibition of K-channels by tetraethylammonium (15 mM) caused the increase of the amplitude of contraction and the negative inotropic effect of NaHS (200 μМ) was preserved. After the activation or inhibition of ATP-dependent K-channels by diazoxide (20 μМ) or glibenclamide (50 μМ), respectively, the negative inotropic effect of NaHS was the same as in control After preliminary application of NaHS glibenclamide (50 μМ) reversed the contraction force to yhe control values. The obtained data suppose that in the isolated rat ventricle exogenous H2S causes a reduction of the force of contraction, which is mediated by the activation of ATP-dependent K-channels
Influence of Hepatic Stellate Cells transduction by adenoviral vector Ad5-optHGF-optFGF-4-RFP on their phenotype in vitro and in vivo
Authors: Sharipova E. I , Titova A. A , Shafigullina A. K , Galyavieva A. R , Garanina E. E , Mavlikeev M. O , Pevnev G. O , Burganova G. R , Titova M. A , Gumerova A. A , Kiyasov A. P , Rizvanov A. A
Published: October 2024

Nowadays gene and cell therapy methods for liver diseases treatment are being actively developed. Genetic modification of cells could be an approach that considerably increases the therapeutic potential of transplanted cells. It is assumed that the genetic manipulation, particularly obtaining and application of cells, that express and overexpress therapeutic factors, could reduce the therapeutic dose of transplanted cells and noticeably enhance therapeutic effects of these cells. However, it remains unclear, how genetic modification influences on cellular phenotype, in this case hepatic stellate cells, and what kind of therapeutic effect will give these cells after transplantation into the organism. The aim of our work was to study the phenotype of hepatic stellate cells after genetic modification by the adenoviral vector Ad5-optHGF-optFGF-4-RFP in vitro and in vivo and after subsequent transplantation into the rats with partial hepatectomy. As a result, it was confirmed that transplantation of hepatic stellate cells, transduced with therapeutic genes, has a positive influence on the process of liver regeneration while the morphology and phenotype of cells remain unchanged. So, we can make a conclusion of safety of this method for use in regenerative medicine
Experimental models for studying of skeletal muscles regeneration
Authors: Chernova O. N , Korsakov I. N , Samchuk D. P , Pulin A. A , Mavlikeev M. O , Deev R. V , Eremin I. I
Published: October 2024

Striated muscles play an important role in the maintenance in the maintenance of locomotion, ventilation, mechanical protection, the inner organs support, a common system of energy exchange etc. Skeletal muscle tissue is exposed to various external factors which cause notable damage to skeletal tissue as a result of mechanical injury (contusion, compression, laceration), inflammation as an implication of infectious agents and autoimmune process, toxic effects of various chemical substances. Besides the external causes, genes' defects that code muscle protein components have influence on the muscles too. These defects lead to muscular dystrophies (Duchenne Becker muscular dystrophy, dysferlinopathy, calpainopathy etc.). In condition of serious injuries the cambial reserve by means of myosatellite cells and other myogenic cells usually does not provides hysto-and organotypic skeletal muscles regeneration. This fact determines development of new methods for induction of regeneration striated muscles and, in turn, requires amplification of using experimental models of muscles injury for studying regeneration of skeletal muscles The aim of this review is comparative description of experimental models applied for studying of skeletal muscles regeneration after its damage
Decellularized rat heart matrix as a basis for creation of tissue engineered heart
Authors: Sotnichenko A. S , Gubareva E. A , Gilevich I. V , Kuevda E. V , Krasheninnikov S. V , Grigoriev T. E , Chvalun S. N , Macchiarini P.
Published: October 2024

Development of bioengineered scaffolds of internal organs is one of the priority areas of tissue engineering. Decellularization allows to obtain biological (natural) scaffolds while preserving extracellular matrix and three-dimensional structure of organs. The primary goals of the present research were to investigate pathological characteristics of the decellularized rat heart scaffold and evaluate adhesion and viability of multipotent mesenchymal stromal cells (MMSC) during recellularization. Rat hearts were decellularized using a modified detergent-enzymatic method including sodium deoxycholate and DNAse. The results of morphological studies have confirmed the safety of extracellular matrix proteins and patency of the coronary vessels. Mechanical testing of decellularized and native samples of rat heart showed an increase of mechanical properties of the matrix during decellularization. During the conducted experiments on recellularization of obtained scaffold has been shown that the extracellular matrix was not toxic for MMSC which were viable and maintained their metabolic activity during prolonged cultivation on the scaffold.
Prospects for tissue engineered bile duct
Authors: Dyuzheva T. G , Lyundup A. V , Klabukov I. D , Chvalun S. N , Grigorev T. E , Shepelev A. D , Tenchurin T. H , Krasheninnikov M. E , Oganesyan R. V
Published: October 2024

Intraoperative bile duct injures requiring its repair observed in 0. 05-2. 7% of patients, who underwent cholecystectomy due to cholelithiasis Lots of patients require reconstructive bile duct surgery given that cholecystectomy is the second most common surgery in the abdominal region, and more than 1 mln operations are made all over the world per year. Previously stitching of the crossed bile duct edges was used, but in most cases this entailed the bile duct stricture and disturbance of the bile outflow. At present, the standard surgery includes suturing of the duct with small intestine, but such a reconstruction, in turn, can lead to liver abscess, biliary cirrhosis and increased risk of cholangiocarcinoma. in this review, we consider the possibility of creating fragments of tissue-engineered bile duct that involves the use multilayer tissue-engineered structures consisting of a composite matrix, cells and signaling molecules that stimulate local proliferation and neovascularization.
Preand posttranscriptional genetic information modification in muscular dystrophy treatment
Authors: Yakovlev I. A , Deev R. V , Solovyeva V. V , Rizvanov A. A , Isaev A. A
Published: October 2024

Nowadays, a whole range of genetherapeutic methods is being used to restore a lost protein function due to mutation, a big number of preclinical and clinical studies of potential drugs that may allow to implement an etiotropic approach is being performed. 0ne of the most prevalent and socially significant groups of genetic pathologies is muscular dystrophy, including such diseases as Duchenne muscular dystrophy and dysfelinopathy. Despite a large number of studies in this field, there is no effective method of gene therapy for these diseases yet. This work is intended to review main genetherapeutic methods in myodystrophy treatment, especially pre- and posttranscriptional genetic (biosynthetic) information modification, and analyze most optimal of them.
Biological activity comparative evaluation of the gene-activated bone substitutes made of octacalcium PHOSPHATE AND PLASMID DNA CARRYING VEGF AND SDF GENES: PART 1 - IN VITRO
Authors: Bozo I. Y , Maiorova K. S , Drobyshev A. Y , Rozhkov S. I , Volozhin G. A , Eremin I. I , Komlev V. S , Smirnov I. V , Rizvanov A. A , Isaev A. A , Popov V. K , Deev R. V
Published: October 2024

High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor-1а (SDF-1a). The aim of the study was to evaluate the cytotoxicity of the gene-activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo. свойств и обладали специфической активностью в виде увеличения экспрессии терапевтических генов. Однако дальнейшие исследования необходимы для детализации выявленных особенностей и оценки реализуемости биологического действия in vivo.
Activity of NOTCH-signaling pathway after subtotal liver resection in rats
Authors: Elchaninov A. V , Fatkhudinov T. Kh , Kananykhina E. Y , Arutyunyan I. V , Makarov A. V , Knyazeva L. A , Bolshakova G. B , Sukhikh G. T
Published: October 2024

N otch-signaling pathway is critical in the regulation of proliferation and differentiation of mammalian cells. Data on the activity of notch-signaling pathway after liver subtotal resection in rats have not been published yet. After subtotal liver resection in rat, the expression of notch1, notch2 and notch-targets genes (sox9, hes1, yap) was assessed with the polymerase chain reaction, immunohistochemistry and western blot. After subtotal liver resection in rat notch1, notch2, yap were downregulated and sox9, hes1 upregulated. Downregulation of notch1 and notch2 is a necessary condition for the activation of hepatocyte proliferation. Upregulation of notch-targets genes such as sox9 and hes1 it is a probably sign of deep dedifferentiation of hepatocytes and preparing them for proliferation than their transdifferentiation in cholangiocytes.
Histological features of the lipograft with platelet-rich plasma after subcutaneous transplantation in vivo
Authors: Dzampaeva I. R , Gaivoronskiy I. V , Krainik I. V , Drobyshev A. Y , Bozo I. Y , Glushko A. V , Deev R. V
Published: October 2024

Autologous adipose tissue transplantation is one of the most common methods of soft tissue volume and shape correction However, the effect of fat grafting is short due to the low survival rate of a fat graft This study was designed to evaluate the influence of the platelet-rich plasma (PRP) on the dynamics of involutive changes of the fat graft in an experimental model with subcutaneous injection in the rabbit ear shell Each animal (n = 9) underwent subcutaneous autologous fat grafting: in the left ear - without PRP, in the right one - mixed with PRP We performed the histological analysis of the materials estimating the number of fat elements, fibrosis processes, and severity of the macrophage-histiocytic reaction (identification of CD163+-cells) in 1, 2, 4, 8, 36 weeks after surgery We found that in the early stages of observation, up to 4 weeks, the signs of fibrosis (the thickness of the connective tissue capsule, interlobular and interadipocyte fibrous septums) were less pronounced in the case of PRP However, further histologic characteristic became similar in the both groups Thus, PRP can have a positive impact on the autologous fat graft survival, but more research is needed to select the optimal PRP processing protocol for autologous fat graft and further analysis of the causes, mechanisms and symptoms of the transplanted fat tissue involution
Ethical and scientific aspects of human embryonic material research: the Great Britain regulations
Authors: Rybtsov S. A , Dumacheva E. V , Dumachev D. V , Mustafin I. G , Kagansky A. M , Rybtsova N. N , Zhdanov R. I
Published: October 2024

We analyze the ethical and scientific issues of human embryonic specimen and its utilization for research purposes. Human embryonic specimens are the source of stem cells which are the foundation for all organs and tissue formation. The analysis of human embryonic specimens promises to obtain the essential knowledge about human development and reveal the causes of human development pathology. Ethical and scientific problems of human embryonic specimens donation and research are debated here We review the impact that human embryonic specimens impose on scientific research, usage restrictions, risk assessment, research personnel and donor protection in view of the British, and other European publications, case reports, legislation, regulations and guidelines This work is focused on the discussion of different aspects of donation and usage of human embryonic specimens obtained after the elective medical termination of pregnancy We discuss suggestions for improvement of the ethical and scientific regulations for the work with human embryonic donor material in Russian Federation.
Changes of liver microstructure after partial hepatectomy in rats
Authors: Gazizov I. M , Kaligin M. S , Andreeva D. I , Yilmaz T. S , Gumerova A. A , Kiassov A. P
Published: October 2024

Ability of mammalian liver to regenerate is one of the favorite examples of “regenerative medicine”. At the same time liver regeneration can not be viewed as a simple hypertrophy, it must have some appropriate steps. Understanding of these processes is crucial for correct interpretation of liver therapy results, especially after cellular therapy. But, unfortunately, original and first-hand data regarding changes in liver microstructure during regeneration is relatively scarce. This work was dedicated to study changes of liver microstructure during liver regeneration after partial hepatectomy in rats. We analyzed proliferative processes, perisinusoidal cells involvement, sizes of classical hepatic lobules, participation of bile ducts, branches of afferent and efferent hepatic vessels in liver regeneration on 1, 2, 3, 5, 7 postoperative days. Our results have shown that liver microstructure during regeneration after partial hepatectomy undergoes two stages: hypertrophy of hepatic lobules by proliferation of liver cells until 4th day and division of hepatic lobules by branching of bile ducts, hepatic artery, portal and central veins from 4th until 7th postoperative day.