111 research outputs found
Production of Ferroalloys and Recycling in the Continuous Oxygen Reactor
A new technology for the production of ferronickel in a new type of unit β a continuous oxygen reactor (COR). The heat source of the process is heat from the afterburning of the exhaust gases. High recovery rate is achieved by carrying out the recovery process in the ore-coal briquettes. Briquettes are located on a carbon substrate. The products are metal and slag granules. The process is characterized by satisfactory performance and low cost of ferronickel.
Keywords: ferroalloy industry, continuous oxygen reactor, briquettes, ferronicke
Probable Mechanisms of COVID-19 Pathogenesis
This review paper focuses on the search for innovative directions in the study of COVIDΒ19 viral infection with theΒ purpose of improving the methods of its treatment and vaccination. Thus far, comprehensive data have been obtained onΒ the ability of nonretroviral RNA viruses, including those replicated in the cytoplasm, to integrate fragments of their genomes into the host DNA. This mechanism provided by the reverseΒ transcriptase and integrase of endogenous retroelements leads to the persistence of nonretroviral RNA virusesΒ through the expression of viral proteins by the host genome,Β which may serve as a prerequisite for the survival of such viruses. DNA integration events play a role in the developmentΒ of both the immunological response and protective antiviral responses through the RNA interference system. TheseΒ mechanisms may depend on the phylogenetically ancient fossils of nonretroviral RNA sequences in animal genomes.Β The discovery of SARS-CoV-2 fragments in COVIDΒ19 recovered patients suggests that the pathogenesis of this diseaseΒ may be associated with the integration of SARS-CoV-2 genome fragments in the human genome by means of proteins ofΒ endogenous retroviral elements. This assumption can be confirmed by the data about the development in older patientsΒ of predominantly severe forms of COVIDΒ19 with βhyperactiveβ immune reactions, which normally weaken with ageing. This may be attributed to ageΒrelated abnormal activation ofΒ retrocells, which contribute to reverse transcriptionΒ and integration of exogenous viruses. This assumption is supported by the presence of coronavirus components in theΒ nuclei of infected cells and the change in the expression of LINEΒ1 in the lung tissue cells of SARS patients. Due to theΒ probable role of retrocells in the COVIDΒ19 pathogenesis, LINEΒ1 reverse transcriptase inhibitors and targeted therapyΒ using microRNAs may be offered as promising treatments for COVIDΒ19
INTERRELATION OF PRIONS WITH NON-CODING RNAS
Prions are alternative infectious conformations for some cellular proteins. For the protein PrPC (PrP β prion protein, Π‘Β βΒ common), a prion conformation, called PrPSc (S β scrapie), is pathological. For example, in mammals the PrPSc prion causes transmissible spongiform encephalopathies accumulating in the brain tissues of PrPSc aggregates that have amyloid properties. MicroRNAs and long non-coding RNAs can be translated into functional peptides. These peptides can have a regulatory effect on genes from which their non-coding RNAs are transcribed. It has been assumed that prions, like peptides, due to the presence of specific domains, can also activate certain non-coding RNAs. Some of the activated non-coding RNAs can catalyze the formation of new prions from normal protein, playing their role in the pathogenesis of prion diseases. Confirmation of this assumption is the presence of the association of alleles of microRNA with the development of the disease, which indicates the role of the specific sequences of noncoding RNAs in the catalysis of prion formation. In the brain tissues of patients with prion diseases, as well as in exosomes containing an abnormal PrPSc isoform, changes in the levels of microRNA have been observed. A possible cause is the interaction of the spatial domains of PrPSc with the sequences of the non-coding RNA genes, which causes a change in their expression. MicroRNAs, in turn, affect the synthesis of long non-coding RNAs. We hypothesize that long noncoding RNAs and possibly microRNAs can interact with PrPC catalyzing its transformation into PrPSc. As a result, the number of PrPSc increases exponentially. In the brain of animals and humans, transposon activity has been observed, which has a regulatory effect on the differentiation of neuronal stem cells. Transposons form the basis of domain structures of long non-coding RNAs. In addition, they are important sources of microRNA. Since prion diseases can arise as sporadic and hereditary cases, and hereditary predisposition is important for the development of pathology, we hypothesize the role of individual features of activation of transposons in the pathogenesis of prion diseases. The activation of transposons in the brain at certain stages of development, as well as under the influence of stress, is reflected in the peculiarities of expression of specific non-coding RNAs that are capable of catalyzing the transition of the PrPC protein to PrPSc. Research in this direction can be the basis for targeted anti-microRNA therapy of prion diseases
The role of transposable elements in the ecological morphogenesis under the influence of stress
In natural selection, insertional mutagenesis is an important source of genome variability. Transposons are sensors of environmental stress effects, which contribute to adaptation and speciation. These effects are due to changes in the mechanisms of morphogenesis, since transposons contain regulatory sequences that haveΒ cisΒ andΒ transΒ effects on specific protein-coding genes. In variability of genomes, the horizontal transfer of transposons plays an important role, because it contributes to changing the composition of transposons and the acquisition of new properties. Transposons are capable of site-specific transpositions, which lead to the activation of stress response genes. Transposons are sources of non-coding RNA, transcription factors binding sites and protein-coding genes due to domestication, exonization, and duplication. These genes contain nucleotide sequences that interact with non-coding RNAs processed from transposons transcripts, and therefore they are under the control of epigenetic regulatory networks involving transposons. Therefore, inherited features of the location and composition of transposons, along with a change in the phenotype, play an important role in the characteristics of responding to a variety of environmental stressors. This is the basis for the selection and survival of organisms with a specific composition and arrangement of transposons that contribute to adaptation under certain environmental conditions. In evolution, the capability to transpose into specific genome sites, regulate gene expression, and interact with transcription factors, along with the ability to respond to stressors, is the basis for rapid variability and speciation by altering the regulation of ontogenesis. The review presents evidence of tissue-specific and stage-specific features of transposon activation and their role in the regulation of cell differentiation to confirm their role in ecological morphogenesis
Involvement of transposable elements in neurogenesis
The article is about the role of transposons in the regulation of functioning of neuronal stem cells and mature neurons of the human brain. Starting from the first division of the zygote, embryonic development is governed by regular activations of transposable elements, which are necessary for the sequential regulation of the expression of genes specific for each cell type. These processes include differentiation of neuronal stem cells, which requires the finest tuning of expression of neuron genes in various regions of the brain. Therefore, in the hippocampus, the center of human neurogenesis, the highest transposon activity has been identified, which causes somatic mosai cism of cells during the formation of specific brain structures. Similar data were obtained in studies on experimental animals. Mobile genetic elements are the most important sources of long non-coding RNAs that are coexpressed with important brain protein-coding genes. Significant activity of long non-coding RNA was detected in the hippocampus, which confirms the role of transposons in the regulation of brain function. MicroRNAs, many of which arise from transposon transcripts, also play an important role in regulating the differentiation of neuronal stem cells. Therefore, transposons, through their own processed transcripts, take an active part in the epigenetic regulation of differentiation of neurons. The global regulatory role of transposons in the human brain is due to the emergence of protein-coding genes in evolution by their exonization, duplication and domestication. These genes are involved in an epigenetic regulatory network with the participation of transposons, since they contain nucleotide sequences complementary to miRNA and long non-coding RNA formed from transposons. In the memory formation, the role of the exchange of virus-like mRNA with the help of the Arc protein of endogenous retroviruses HERV between neurons has been revealed. A possible mechanism for the implementation of this mechanism may be reverse transcription of mRNA and site-specific insertion into the genome with a regulatory effect on the genes involved in the memory
The relationship of lamins with epigenetic factors during aging
The key factor of genome instability during aging is transposon dysregulation. This may be due to senile changes in the expression of lamins, which epigenetically modulate transposons. Lamins directly physically interact with transposons. Epigenetic regulators such as SIRT7, BAF, and microRNA can also serve as intermediaries for their interactions. There is also an inverse regulation, since transposons are sources of miRNAs that affect lamins. We suggest that lamins can be attributed to epigenetic factors, since they are part of the NURD, interact with histone deacetylases and regulate gene expression without changing the nucleotide sequences. The role of lamins in the etiopathogenesis of premature aging syndromes may be associated with interactions with transposons. In various human cells, LINE1 is present in the heterochromatin domains of the genome associated with lamins, while SIRT7 facilitates the interaction of this retroelement with lamins. Both retroelements and the nuclear lamina play an important role in the antiviral response of organisms. This may be due to the role of lamins in protection from both viruses and transposons, since viruses and transposons are evolutionarily related. Transposable elements and lamins are secondary messengers of environmental stressors that can serve as triggers for aging and carcinogenesis. Transposons play a role in the development of cancer, while the microRNAs derived from them, participating in the etiopathogenesis of tumors, are important in human aging. Lamins have similar properties, since lamins are dysregulated in cancer, and microRNAs affecting them are involved in carcinogenesis. Changes in the expression of specific microRNAs were also revealed in laminopathies. Identification of the epigenetic mechanisms of interaction of lamins with transposons during aging can become the basis for the development of methods of life extension and targeted therapy of age-associated cancer
Specific Features of Ovarian Cancer Metastasis
This review presents data on the predominant mechanisms of metastatic progression of ovarian cancer. TheΒ morphological and functional features of the greater omentum are shown, both promoting the spread ofΒ cancer cells and having an antitumour effect. The ratio of these two mutually opposite properties depends onΒ the cellular composition, theΒ content of extracellular matrix molecules and the biomechanical properties of the greater omentum during carcinogenesis. Milky spots are the main site of cancer cell implantation. They differΒ from lymph nodes in a simpler structureΒ and a unique cellular composition (macrophages, B cells, CD4+ and CD8+ T lymphocytes, other immune cells) changing significantly during metastasis. Π2Βmacrophages,Β adipocytes, CD33+ and CD4+ CD25high CD127low Π’ΒsuppressorsΒ promote migration, invasion, growth and colonization of cancer cells. The majority of the molecules synthesized inΒ the greater omentum during metastasis also stimulate this process. The exceptions are EΒcadherin, CXCL10, CXCL11,Β CXCR3, which inhibit the growth of tumour foci. In addition, CD8+ T lymphocytes and M1 macrophages also have antitumorΒ effects. Since ovarian cancer is characterized by high mortality, mainly due to metastases, the issue ofΒ optimizingΒ methods for predicting the treatment effectiveness depending on the cellular composition and expression of specificΒ molecules in the milky spots of the greater omentum is urgent. These indicators can be applied in clinical practice usingΒ molecular genetic and immunohistochemical methods. In order to determine the need for omenectomy in the surgicalΒ treatment of ovarian cancer and to predict the outcome, it is advisable to study the morphological and functional properties of the greater omentum and to determine the number of immunocompetent cells and the nature of the expressionΒ of genes associated with the worst prognosis, those encoding activinΒA, NΒcadherin, CCL23, CD36, CD44, CFΒ1/MΒCSF,Β FABP4, GROΒΞ±, GROΒΞ², ILΒ8, ITGA2, MMP9, TP53, VEGF, VEGFR. These molecules are associated with adhesion andΒ angiogenesis systems that play a key role in metastasis. Promising directions in the therapy of metastatic ovarian cancerΒ can be stimulation of the transition of M2Β to M1Βmacrophages, activation of the antiΒtumour antigenΒspecific responseΒ of CD8+ T cells using phagocytes, adaptive transfer of natural killer cells, the use of inhibitors of Wnt pathways,Β CCR1,Β CD36, FABP4, PAD4, ITGA2
Π ΠΎΠ»Ρ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ² Π² ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠ°ΡΠΎΠ·Π° 1-Π³ΠΎ ΡΠΈΠΏΠ°
The article describes the role of epigenetic processes in the tumorigenesis of neurofibromatosis type 1. The clinical manifestations of neurofibromatosis type 1 is characterized by a pronounced polymorphism erased from with single neurofibromas to severe forms with thousandsΒ of tumors and complications even in patients with the same mutations. More than 1400 mutations in the NF1 gene have been reported, but have not yet identified genotype-phenotype correlations. Detected in the majority of neurofibromas mutation of the second allele of the gene NF1 and loss of heterozygosity may result from common disorders of genome stability and cell cycle regulation. Chance of tissue-specificΒ inactivation of the second allele is extremely low and can not prove the detection of neurofibromas in most patients with neurofibromatosis type 1. At the same time, the role of epigenetic factors for blocking of oncosupressors has been proven and can be applied to the developmentΒ of malignant tumors and neurofibromas. This assumption is proved by the fact that the majority of neurofibromas are formed in puberty, while inheriting the disease from mother to clinical manifestations more severe. This review presents the research on the role of miRNAs and specific methylation in the promoter region of NF1 tumorogenesis in neurofibromatosis type 1. Mutations in the NF1 gene are of great importance in the development of many malignancies. Due to the possibility of pharmacological correction of activity of microRNAs using antisense sequences, the study of epigenetic processes in neurofibromatosis type 1 promising to diagnose and treat not only the disease but also sporadic malignancies.Π ΠΎΠ±Π·ΠΎΡΠ½ΠΎΠΉ ΡΡΠ°ΡΡΠ΅ ΠΎΠΏΠΈΡΠ°Π½Π° ΡΠΎΠ»Ρ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ² Π² ΡΡΠΌΠΎΡΠΎΠ³Π΅Π½Π΅Π·Π΅ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠ°ΡΠΎΠ·Π° 1-Π³ΠΎ ΡΠΈΠΏΠ° (ΠΠ€1). ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΊΠ°ΡΡΠΈΠ½Π° ΠΠ€1 Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ΅ΡΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠΎΠΌ β ΠΎΡ ΡΡΠ΅ΡΡΡΡ
ΡΠΎΡΠΌ Ρ Π΅Π΄ΠΈΠ½ΠΈΡΠ½ΡΠΌΠΈ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠ°ΠΌΠΈ Π΄ΠΎ ΡΡΠΆΠ΅Π»ΡΡ
ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΉ Ρ ΡΡΡΡΡΠ°ΠΌΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ ΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌΠΈ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΡΠΌΠΈ. ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ Π±ΠΎΠ»Π΅Π΅ 1400 ΡΠΈΠΏΠΎΠ² ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ NF1, Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»Π΅ΠΉ Π½Π΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π³Π΅Π½ΠΎΡΠ΅Π½ΠΎΡΠΈΠΏΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΉ. ΠΡΠΎΡΠΎΠ΅ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠΎΠ±ΡΡΠΈΠ΅ Π² Π³Π΅Π½Π΅ NF1, Π²ΡΡΠ²Π»ΡΠ΅ΠΌΠΎΠ΅ Π² ΡΠ²Π°Π½Π½ΠΎΡΠΈΡΠ°Ρ
Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌ, ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠΌ ΠΎΠ±ΡΠΈΡ
Π½Π°ΡΡΡΠ΅Π½ΠΈΠΉ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ Π³Π΅Π½ΠΎΠΌΠ° ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π°. ΠΠ΅ΡΠΎΡΡΠ½ΠΎΡΡΡ ΡΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈΠ½Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ Π²ΡΠΎΡΠΎΠ³ΠΎ Π°Π»Π»Π΅Π»Ρ ΡΡΠ΅Π·Π²ΡΡΠ°ΠΉΠ½ΠΎ ΠΌΠ°Π»Π° ΠΈ Π½Π΅ ΠΌΠΎΠΆΠ΅Ρ ΠΎΠ±ΡΡΡΠ½ΠΈΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Ρ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π° Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ€1. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ ΡΠΎΠ»Ρ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ² Π² Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠΎΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½Π° ΠΈ ΠΌΠΎΠΆΠ΅Ρ ΠΈΠΌΠ΅ΡΡ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, Π² ΠΏΠΎΠ»ΡΠ·Ρ ΡΠ΅Π³ΠΎ Π³ΠΎΠ²ΠΎΡΠΈΡ Π·Π°ΠΊΠΎΠ½ΠΎΠΌΠ΅ΡΠ½ΠΎΠ΅ Π½Π°ΡΠ°Π»ΠΎ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌ Π² ΠΏΡΠ±Π΅ΡΡΠ°ΡΠ½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅, ΡΡΡΠΆΠ΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΈ ΠΏΡΠΈ Π½Π°ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΎΡ ΠΌΠ°ΡΠ΅ΡΠΈ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΎΠ»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠΌΠΎΡΠΎΡΠ½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ NF1 Π² ΡΡΠΌΠΎΡΠΎΠ³Π΅Π½Π΅Π·Π΅ ΠΏΡΠΈ ΠΠ€1, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΎΠ»ΠΈ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ NF1 Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠΏΠΎΡΠ°Π΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ. Π ΡΠ²ΡΠ·ΠΈ Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡΡ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°Π½ΡΠΈΡΠΌΡΡΠ»ΠΎΠ²ΡΡ
ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΠΏΡΠΈ ΠΠ€1 ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎ Π΄Π»Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π΄Π°Π½Π½ΠΎΠΉ Π±ΠΎΠ»Π΅Π·Π½ΠΈ, Π½ΠΎ ΠΈ ΡΠΏΠΎΡΠ°Π΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ
ΠΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠ°ΡΠΎΠ·Π° I ΡΠΈΠΏΠ° Π² Π Π΅ΡΠΏΡΠ±Π»ΠΈΠΊΠ΅ ΠΠ°ΡΠΊΠΎΡΡΠΎΡΡΠ°Π½
Neurofi bromatosis type I (NF1) is a common hereditary tumour syndrome with autosomal dominant type of inheritance. Average worldwide incidence rate of NF1 is 1:3000, equal in men and women. Th e disease develops with a heterozygous mutation in the oncosupressor neurofi bromin-encoding gene NF1. No NF1-associated most common mutations have been found, with over 1400 mutations being described along the gene. No clinical and genetic correlations are observed for NF1, and its symptoms may vary considerably within same inheritance group. Typical NF1 manifestations include pigmented patches and multiple cutaneous or subcutaneous neurofi bromas, oft en disfi guring in degree. Pathogenetic therapy for NF1 is not yet developed, whilst surgical tumourectomy may lead to recurrence and new tumour development in other localities on the body. Molecular genetic research on putative interfaces with epigenetic factors and gene expression patterns may open promising future avenues. Further, establishing a marker NF1 mutation in NF1 patients will allow secondary prevention of the disease. A survey of russian NF1-related literature reveals prevalence of individual clinical case descriptions. In the Russian Federation, studies of NF1-associated mutations in gene NF1 originate from Moscow and Bashkortostan, which sets off advancement of Bashkir medical genetics and urges further developments. In Bashkortostan, 10 NF1-associated mutations were described from 16 patients. Th e reported mutations Ρ.1278G>A (p.Trp426Π₯), Ρ.1570G>A (p.Glu540Lys), Ρ.1973_1974delTC (Ρ.Leu658ProfsX10), Ρ.3526_3528delAGA (p.Arg1176del), Ρ.3826delC (Ρ.Arg1276GlufsX8), Ρ.4514+5G>A, c.5758_5761delTTGA (p.Leu1920AsnfsX7) in the NF1 gene are new to science. Further research into other genesβ and microRNA expression in patients with various clinical manifestations of NF1 should be aimed at discovering its possible involvement in disease pathogenesis.ΠΠ΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠ°ΡΠΎΠ· I ΡΠΈΠΏΠ° (ΠΠ€1) β ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΠΉ Π½Π°ΡΠ»Π΅Π΄ΡΡΠ²Π΅Π½Π½ΡΠΉ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌ Ρ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΎ-Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΠ½ΡΠΌ ΡΠΈΠΏΠΎΠΌ Π½Π°ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. Π§Π°ΡΡΠΎΡΠ° Π²ΡΡΡΠ΅ΡΠ°Π΅ΠΌΠΎΡΡΠΈ ΠΠ€1 Π² ΡΡΠ΅Π΄Π½Π΅ΠΌ ΠΏΠΎ ΠΌΠΈΡΡ ΡΠΎΡΡΠ°Π²Π»ΡΠ΅Ρ 1:3000 Ρ ΡΠ°Π²Π½ΠΎΠΉ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡΡ Ρ ΠΌΡΠΆΡΠΈΠ½ ΠΈ ΠΆΠ΅Π½ΡΠΈΠ½. ΠΡΠΈΡΠΈΠ½Π° Π±ΠΎΠ»Π΅Π·Π½ΠΈ β Π³Π΅ΡΠ΅ΡΠΎΠ·ΠΈΠ³ΠΎΡΠ½Π°Ρ ΠΌΡΡΠ°ΡΠΈΡ Π² Π³Π΅Π½Π΅ NF1, ΠΊΠΎΡΠΎΡΡΠΉ ΠΊΠΎΠ΄ΠΈΡΡΠ΅Ρ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌΠΈΠ½. ΠΠ»Ρ ΠΠ€1 Π½Π΅ Π½Π°ΠΉΠ΄Π΅Π½ΠΎ ΠΌΠ°ΠΆΠΎΡΠ½ΡΡ
ΠΌΡΡΠ°ΡΠΈΠΉ, ΠΎΠΏΠΈΡΠ°Π½ΠΎ Π±ΠΎΠ»Π΅Π΅ 1400 ΠΈΡ
ΡΠΈΠΏΠΎΠ² Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΎΠ±Π»Π°ΡΡΡΡ
Π³Π΅Π½Π°. ΠΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΉ Π΄Π»Ρ ΠΠ€1 Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½ΠΎ, Π΄Π°ΠΆΠ΅ Π² ΠΎΠ΄Π½ΠΎΠΉ ΠΈ ΡΠΎΠΉ ΠΆΠ΅ ΡΠ΅ΠΌΡΠ΅ ΡΠΈΠΌΠΏΡΠΎΠΌΠ°ΡΠΈΠΊΠ° Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΌΠΎΠΆΠ΅Ρ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ. Π₯Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΠΌΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡΠΌΠΈ ΠΠ€1 ΡΠ²Π»ΡΡΡΡΡ ΠΏΠΈΠ³ΠΌΠ΅Π½ΡΠ½ΡΠ΅ ΠΏΡΡΠ½Π° ΠΈ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²ΠΎ ΠΊΠΎΠΆΠ½ΡΡ
ΠΈΠ»ΠΈ ΠΏΠΎΠ΄ΠΊΠΎΠΆΠ½ΡΡ
Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌ, Π½Π΅ΡΠ΅Π΄ΠΊΠΎ ΠΎΠ±Π΅Π·ΠΎΠ±ΡΠ°ΠΆΠΈΠ²Π°ΡΡΠΈΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
. ΠΠ°ΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΠ€1 ΠΏΠΎΠΊΠ° Π½Π΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π°, Π° Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ΄Π°Π»Π΅Π½ΠΈΠ΅ Π½Π΅ΠΉΡΠΎΡΠΈΠ±ΡΠΎΠΌ ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΈΠ²Π΅ΡΡΠΈ ΠΊ ΡΠ΅ΡΠΈΠ΄ΠΈΠ²Ρ ΠΈ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΡ Π½ΠΎΠ²ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ Π² Π΄ΡΡΠ³ΠΈΡ
ΠΎΠ±Π»Π°ΡΡΡΡ
ΡΠ΅Π»Π°. ΠΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ°ΠΌΠΈ Π΄Π»Ρ Π±ΠΎΡΡΠ±Ρ Ρ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠΎΠ³ΡΡ ΡΡΠ°ΡΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Ρ ΠΏΠΎΠΈΡΠΊΠΎΠΌ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Π΅ΠΉ Ρ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ°ΠΊΡΠΎΡΠ°ΠΌΠΈ ΠΈ ΠΏΡΠΎΠ΄ΡΠΊΡΠ°ΠΌΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π΄ΡΡΠ³ΠΈΡ
Π³Π΅Π½ΠΎΠ². ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π½Π°Ρ
ΠΎΠΆΠ΄Π΅Π½ΠΈΠ΅ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ Π² Π³Π΅Π½Π΅ NF1 Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠ€1 ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡ Π²ΡΠΎΡΠΈΡΠ½ΡΡ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΡ Π±ΠΎΠ»Π΅Π·Π½ΠΈ. ΠΠ½Π°Π»ΠΈΠ· ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ±Π»ΠΈΠΊΠ°ΡΠΈΠΉ ΠΏΠΎ ΠΠ€1 ΠΏΠΎΠΊΠ°Π·Π°Π» ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°Π½ΠΈΠ΅ ΡΡΠ°ΡΠ΅ΠΉ Ρ ΠΎΠΏΠΈΡΠ°Π½ΠΈΠ΅ΠΌ ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ
ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ»ΡΡΠ°Π΅Π². Π Π ΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ Π€Π΅Π΄Π΅ΡΠ°ΡΠΈΠΈ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Ρ ΡΠ°Π±ΠΎΡΡ ΠΎ ΠΏΠΎΠΈΡΠΊΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ NF1 Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ€1 ΡΠΎΠ»ΡΠΊΠΎ Π² ΠΠΎΡΠΊΠ²Π΅ ΠΈ Π² ΠΠ°ΡΠΊΠΎΡΡΠΎΡΡΠ°Π½Π΅. ΠΡΠΎ Π³ΠΎΠ²ΠΎΡΠΈΡ ΠΎ Π²ΡΡΠΎΠΊΠΎΠΌ ΡΡΠΎΠ²Π½Π΅ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ Π³Π΅Π½Π΅ΡΠΈΠΊΠΈ Π² Π½Π°ΡΠ΅ΠΉ ΡΠ΅ΡΠΏΡΠ±Π»ΠΈΠΊΠ΅ ΠΈ ΠΎ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠΈΡ
ΡΠ°Π±ΠΎΡ. Π Π Π΅ΡΠΏΡΠ±Π»ΠΈΠΊΠ΅ ΠΠ°ΡΠΊΠΎΡΡΠΎΡΡΠ°Π½ Π²ΡΡΠ²Π»Π΅Π½ΠΎ 10 ΠΌΡΡΠ°ΡΠΈΠΉ Ρ 16 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ€1. ΠΡΡΠ°ΡΠΈΠΈ Ρ.1278G>A (p.Trp426Π₯), Ρ.1570G>A (p.Glu540Lys), Ρ.1973_1974delTC (Ρ.Leu658ProfsX10), Ρ.3526_3528delAGA (p.Arg1176del), Ρ.3826delC (Ρ.Arg1276GlufsX8), Ρ.4514+5G>A, c.5758_5761delTTGA (p.Leu1920AsnfsX7) Π² Π³Π΅Π½Π΅ NF1 ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Ρ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ Π² ΠΌΠΈΡΠ΅. ΠΠ»Π°Π½ΠΈΡΡΠ΅ΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄ΡΡΠ³ΠΈΡ
Π³Π΅Π½ΠΎΠ² ΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡΠΌΠΈ ΠΠ€1 Π΄Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΈΡ
Π²Π»ΠΈΡΠ½ΠΈΡ Π½Π° ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π· Π±ΠΎΠ»Π΅Π·Π½ΠΈ
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