154 research outputs found
Evaluation of indicators of entrepreneurial potential in 2018
Entrepreneurial potential of the population is largely determined by how adults evaluate their intentions in terms of creating their own business. The purpose of the study was to assess the existing indicators in 2018 that characterize the potential entrepreneurial activity of the population in different countries. The self-assessment of people on such factors as their ability and ability to create their own businesses, entrepreneurial purposes, fear of failure in this activity, as well as the presence of familiar entrepreneurs were considered as the estimated indicators. The study used information from the Global entrepreneurship monitor for 2018 for 48 countries. Three hypotheses were tested using mathematical models representing the density functions of the normal distribution. Five indicators of entrepreneurial potential were used to determine their average values for the countries under consideration. Countries with high and low values of indicators were identified. A comparative analysis of the entrepreneurial potential in Russia and foreign countries is carried out
Ethnic characteristics of bone remodeling in female patients with type 2 diabetes mellitus
Background: Structural and metabolic disorders of bone tissue in women with T2DM have no clinical manifestations, but they are accompanied by the risk of fractures.Aim: To study the parameters of bone metabolism, BMD and microarchitectonics in female patients with T2DM in the Buryat population.Materials and methods: The observational single-center one-stage controlled study included 73 women with T2DM, which were divided into 2 groups depending on the functional state of the ovaries (reproductive and postmenopausal periods). In each group, subgroups of the Buryat and Russian populations were identified. The first group included 34 patients with T2DM of the reproductive period: 16 from the Buryat population and 18 from the Russian population. The second group consisted of 39 postmenopausal patients with T2DM: 17 from the Buryat population and 22 from the Russian population. The study of BMD in the lumbar spine (L1-L4), femoral neck (Neck), in the proximal femur (Total hip), trabecular bone score (TBS), serum osteocalcin (OC), N-terminal propeptide type 1 procollagen was carried out (P1NP), vitamin D 25 (OH), blood plasma type I collagen C-terminal telopeptide (Ξ²-Cross laps) and ionized calcium (iCa).Results: In female patients with T2DM of the reproductive age of the Buryat population, an increase in both markers of osteosynthesis P1NP (p=0.035), OC (p=0.047), and bone resorption Ξ²-Cross laps (p=0.040) was found relative to the similar group of the Russian population. In women with T2DM in the postmenopausal period of the Buryat population, there was also an increase in P1NP (p = 0.016), OC (p = 0.048), Ξ²-Cross laps (p = 0.020) compared with the group of postmenopausal women in the Russian population. Structural disorders, characterized by a decrease in TBS, were detected only in the postmenopausal period in female patients of the Buryat population compared to women in the Russian population (p = 0.029).Comparative analysis among women with T2DM of the Buryat population, depending on the functional state of the ovaries, showed that activation of bone remodeling with an increase in P1NP (p = 0.019), OC (p = 0.004) and Ξ²-Cross laps (p = 0.004) is characteristic of postmenopausal women accompanied by a decrease in BMD Neck (p = 0.006), BMD Total hip (p = 0.003), BMD L1-L4 (p = 0.049) and TBS (p = 0.020) relative to female patients with T2DM in the reproductive period.Conclusion: In women with T2DM in the Buryat population, both in the reproductive and postmenopausal periods, an increase in bone remodeling markers and BMD stability was found when compared with the corresponding groups of patients in the Russian population. The postmenopausal period was characterized by an additional decrease in TBS in patients with T2DM in the Buryat population relative to women in the Russian population
Experience in implementing a program for basic life support and available automated defibrillation in a cancer center
Unified approaches to ensuring the chain of survival can improve the patientβs prognosis both in out-of-hospital and in-hospital cardiac arrest.Aim. To discuss practical issues of introducing a program for the availability of automated external defibrillation in a cancer center.Material and methods. For four years, our healthcare facility has been implementing a training program for basic and advanced life support according to the European Resuscitation Council standards, combined with the creation and development of an infrastructure for the availability of automatic defibrillation. A roadmap and infrastructure were developed for the project implementation.Results. In 2018-2022, 229 employees (114 doctors, 85 nurses and 30 nonmedical workers) were trained under the basic life support program. Fifteen defibrillators were placed in various units. During the specified period, first aid in case of sudden cardiac arrest using an automated external defibrillator before the resuscitation team arrival was independently provided by doctors and nurses of departments three times. To implement training in the continuous education system, the curriculum has passed the examination and accreditation in the edu. rosminzdrav system.Conclusion. The development and implementation of such initiatives requires significant organizational and methodological work, including continuous education system. However, in our opinion, this is an extremely useful tool for improving the safety and quality of medical care
Π’Π΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΎΡΠΈΡΡΠΊΠΈ ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½ΡΡ Π²ΠΎΠ΄ ΠΎΡ ΡΠ°ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΡ Π½Π΅ΡΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ²
The priority in the oil industry is to reduce the technogenic load on environmental components. Modern technologies allow minimizing the negative impact on water bodies, soils, vegetation, etc. However, the development of effective technical solutions aimed at purification of underground water from oil products is still in progress. There are mechanical, physical-chemical, and biological methods of oil pollution control. Each method has advantages and limitations and can be used in different situations. The technology of groundwater treatment based on biotechnological method and dosed oxygen supply is proposed. The recommended solution can be used as an independent environmental protection measure or in addition to existing ones.ΠΡΠΈΠΎΡΠΈΡΠ΅ΡΠΎΠΌ Π² Π½Π΅ΡΡΡΠ½ΠΎΠΉ ΠΏΡΠΎΠΌΡΡΠ»Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ³Π΅Π½Π½ΠΎΠΉ Π½Π°Π³ΡΡΠ·ΠΊΠΈ Π½Π° ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ ΠΎΠΊΡΡΠΆΠ°ΡΡΠ΅ΠΉ ΡΡΠ΅Π΄Ρ. Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΠΎΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π½Π° Π²ΠΎΠ΄Π½ΡΠ΅ ΠΎΠ±ΡΠ΅ΠΊΡΡ, Π³ΡΡΠ½ΡΡ, ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΈ Ρ.Π΄. ΠΠ΄Π½Π°ΠΊΠΎ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΡΠ΅Ρ
Π½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅ΡΠ΅Π½ΠΈΠΉ, Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΡΡ
Π½Π° ΠΎΡΠΈΡΡΠΊΡ ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½ΡΡ
Π²ΠΎΠ΄ ΠΎΡ Π½Π΅ΡΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ², ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°Π΅ΡΡΡ. Π‘ΡΡΠ΅ΡΡΠ²ΡΡΡ ΠΌΠ΅Ρ
Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠ΅, ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ Π±ΠΎΡΡΠ±Ρ Ρ Π½Π΅ΡΡΡΠ½ΡΠΌ Π·Π°Π³ΡΡΠ·Π½Π΅Π½ΠΈΠ΅ΠΌ. ΠΠ°ΠΆΠ΄ΡΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΈΠΌΠ΅Π΅Ρ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π° ΠΈ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½ΠΈΡ, ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ Π² ΡΠ°Π·Π½ΡΡ
ΡΠΈΡΡΠ°ΡΠΈΡΡ
. ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π° ΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡ ΠΎΡΠΈΡΡΠΊΠΈ ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½ΡΡ
Π²ΠΎΠ΄ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π±ΠΈΠΎΡΠ΅Ρ
Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΈ Π΄ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΏΠΎΠ΄Π°ΡΠΈ ΠΊΠΈΡΠ»ΠΎΡΠΎΠ΄Π°. Π Π΅ΠΊΠΎΠΌΠ΅Π½Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΎ ΠΊΠ°ΠΊ ΡΠ°ΠΌΠΎΡΡΠΎΡΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΏΡΠΈΡΠΎΠ΄ΠΎΠΎΡ
ΡΠ°Π½Π½ΠΎΠ΅ ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΠ΅, ΡΠ°ΠΊ ΠΈ Π² Π΄ΠΎΠΏΠΎΠ»Π½Π΅Π½ΠΈΠ΅ ΠΊ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΌ
FRUIT AND BERRY CROPS IN THE ENVIRONMENTS OF THE BUZULUKSKY BOR NATIONAL PARK
Buzuluksky Bor is the name of the largest woodland in the steppe zone (86,600 ha) of Northern Eurasia, and the only one in the Transvolga steppe. Woody vegetation of this forest consists of conifers (70%) and broadleaf trees (30%). Many of the latter produce edible fruits and berries. In addition to indigenous species, a significant part is formed by the introduced ones which have adapted to the specific conditions of this woodland. In 2007, a large area of the pine forest became part of the Buzuluksky Bor National Park
Primary Terminal Haemochromatosis in a 50 Year-Old Patient
Aim. A clinical description of end-stage hereditary haemochromatosis manifested with chronic alcohol abuse.Key points. A 50-yo patient referred with marked general weakness as a major complaint. The patient had a history of long-term alcohol consumption at toxic doses, putative cirrhosis, paroxysmal atrial fibrillation, type 2 diabetes mellitus. The patient's severity on admission was conditioned by marked hypotension. Further examination aimed at excluding occult gastrointestinal bleeding, adrenal insufficiency, decompensated heart failure. Bronze skin and icteric sclerae were positive. Blood tests revealed severe macrocytic hyperchromic anaemia, thrombocytopae-nia, hyperbilirubinaemia, hypoalbuminaemia, hypocoagulation, elevated transaminases, hyponatraemia, elevated creatinine (CKD DPI 63 mL/min), severe hyperferritinaemia. Faecal occult blood test and EGDS for bleeding were negative. Abdominal ultrasound exposed signs of liver cirrhosis and portal hypertension (ascites, splenomegaly). Echocardiographic evidence of dilated cardiomyopathy of all chambers, a reduced 24% ejection fraction at absent acute myocardial infarction. Primary haemochromatosis was suspected upon high ferritin, transferrin iron saturation and multiple organ dysfunction. Genotyping revealed the HFE 845G > A variant diagnostic of haemochromatosis type 1. Clinical diagnosis: Primary disease: haemochromatosis (homozygous variant HFE 845G > A (A/A)): liver cirrhosis, Child-Pugh class C. Portal hypertension: splenomegaly, ascites. Dilated cardiomyopathy. Diabetes mellitus. Complications: multiple organ dysfunction (SOFA 16). Liver failure: jaundice, hypoalbuminaemia, hypocoagulation. Cardiac rhythm and conduction disorder: paroxysmal atrial fibrillation. Acute cardiac failure with underlying CHF IIb, NYHA class 3. Acute renal failure (anuria) with underlying CKD stage 3 (CKD DPI 63 mL/min). Moderate macrocytic hyperchromic anaemia. Acute and chronic adrenal failure. Despite a cardiovascular and renal failure compensation therapy and albumin transfusion, the patient died. Autopsy revealed a marked organ infiltration with haemosiderin (heart, stomach, liver, pancreas, lungs, kidneys, adrenal glands).Conclusion. The case describes a classical clinical manifestation of haemochromatosis: bronze skin hyperpigmentation, liver cirrhosis, diabetes mellitus, cardiomyopathy, adrenal insufficiency. Terminal haemochromatosis, severe cardiac and renal failure decompensation precluded phlebotomy and chelation therapy. A lethal outcome was conditioned by multiple organ dysfunction with underlying massive haemosiderin deposition in most organs
ΠΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π³Π΅ΠΌΠΎΠ±Π»Π°ΡΡΠΎΠ·Π°Ρ
The purpose of the study was to present up-to-date data on the frequency and significance of a number of p53-responsive oncosuppressive micrornas genes methylation in malignant neoplasms of the blood system.Material and methods. The search for available literary sources published in the Pubmed and RISC databases was carried out. A total of 399 articles were found, of which 62 were included in this review.Results. The p53 protein regulates a whole class of microRNAs β highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. ΠicroRNAs play an important role in all cellular processes and can have both oncosuppressive and pro-oncogenic properties. Impaired expression of p53-activated oncosuppressive micrornas in various tumors may be associated with specific epigenetic mechanisms (DNA methylation and histone deacetylation). The review examines the molecular and genetic characteristics of oncosuppressive micrornas functioning in normal hematopoiesis, the violation of expression of which is shown in the development of hemoblastoses, namely: miR-34a, miR-34b/c, miR-145, miR-143 and miR-203. It is known that the transcription of the genes of these microRNAs is carried out and regulated from their own promoters. The latest published research results on the diagnostic, prognostic and clinical significance of gene methylation of the microRNAs under consideration in malignant neoplasms of the blood system are presented. According to literature data, common targets for mir-34a, mir-34b/c, mir-145, mir-143 and miR-203 microRNAs are mRNAs of a number of pro-oncogenes, namely: transcription factor C-MYC, positive cell cycle regulators at the G1/S transition point of CDK4, CDK6 and CYCLIN-D1 phases, anti-apoptotic proteins MDM2, MDM4, BCL2 and MCL1, as well as DNMT3A and DNMT3B methyltransferases and other molecules. In this regard, it should be noted that there are positive feedbacks between p53 and microRNAs activated by it, as well as negative feedbacks between p53-responsive micrornas and C-MYC and DNA methyltransferases.Conclusion. Thus, the data presented in the review clarify the current understanding of the work of the regulatory network of the p53 protein and the micrornas activated by it, and also emphasize the functional association of p53-responsive microRNAs.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΏΡΠ΅Π΄ΡΡΠ°Π²ΠΈΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠ°ΡΡΠΎΡΠ΅ ΠΈ Π·Π½Π°ΡΠ΅Π½ΠΈΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΡΠ΄Π° Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ
ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ
ΡΠΈΡΡΠ΅ΠΌΡ ΠΊΡΠΎΠ²ΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΏΠΎΠΈΡΠΊ Π΄ΠΎΡΡΡΠΏΠ½ΡΡ
Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΡ
Π² Π±Π°Π·Π°Ρ
Π΄Π°Π½Π½ΡΡ
Pubmed ΠΈ Π ΠΠΠ¦. ΠΠ°ΠΉΠ΄Π΅Π½ΠΎ 399 ΡΡΠ°ΡΠ΅ΠΉ, ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
62 Π±ΡΠ»ΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ Π² Π΄Π°Π½Π½ΡΠΉ ΠΎΠ±Π·ΠΎΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ΅Π»ΠΎΠΊ Ρ53 ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅Ρ ΡΠ΅Π»ΡΠΉ ΠΊΠ»Π°ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ β Π²ΡΡΠΎΠΊΠΎΠΊΠΎΠ½ΡΠ΅ΡΠ²Π°ΡΠΈΠ²Π½ΡΡ
ΠΌΠ°Π»ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ» Π ΠΠ, ΠΊΠΎΡΠΎΡΡΠ΅ Π²Π»ΠΈΡΡΡ Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Π³Π΅Π½ΠΎΠ² Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΠΏΡΡΠ΅ΠΌ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ ΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ. ΠΠΈΠΊΡΠΎΠ ΠΠ ΠΈΠ³ΡΠ°ΡΡ Π²Π°ΠΆΠ½ΡΡ ΡΠΎΠ»Ρ Π²ΠΎ Π²ΡΠ΅Ρ
ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ
ΠΈ ΠΌΠΎΠ³ΡΡ ΠΈΠΌΠ΅ΡΡ ΠΊΠ°ΠΊ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΠ΅, ΡΠ°ΠΊ ΠΈ ΠΏΡΠΎΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π½ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΡ
Ρ53 ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»ΡΡ
ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΡΠ²ΡΠ·Π°Π½Ρ ΡΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ (ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΠΠ ΠΈ Π΄Π΅Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π³ΠΈΡΡΠΎΠ½ΠΎΠ²). Π ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ, ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΡΡΡΠΈΡ
ΠΏΡΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΌ ΠΊΡΠΎΠ²Π΅ΡΠ²ΠΎΡΠ΅Π½ΠΈΠΈ, Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΊΠΎΡΠΎΡΡΡ
ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π³Π΅ΠΌΠΎΠ±Π»Π°ΡΡΠΎΠ·ΠΎΠ², Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: miR-34a, miR-34b/Ρ, miR-145, miR-143 ΠΈ miR-203. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΡΠΈΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈ ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅ΡΡΡ Ρ ΡΠΎΠ±ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠΎΠΌΠΎΡΠΎΡΠΎΠ². ΠΡΠΈΠ²Π΅Π΄Π΅Π½Ρ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ, ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌΡ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°Π΅ΠΌΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡΡ
ΡΠΈΡΡΠ΅ΠΌΡ ΠΊΡΠΎΠ²ΠΈ. Π‘ΠΎΠ³Π»Π°ΡΠ½ΠΎ Π΄Π°Π½Π½ΡΠΌ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΡΠ°ΡΡΡΠΌΠΈ ΠΎΠ±ΡΠΈΠΌΠΈ ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ Π΄Π»Ρ ΠΌΠΈΠΊΡΠΎΠ ΠΠ miR-34a, miR-34b/Ρ, miR-145, miR-143 ΠΈ miR-203 ΡΠ²Π»ΡΡΡΡΡ ΠΌ-Π ΠΠ ΡΡΠ΄Π° ΠΏΡΠΎΠΎΠ½ΠΎΠΊΠΎΠ³Π΅Π½ΠΎΠ², Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° C-MYC, ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π° Π² ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΠΎΠΉ ΡΠΎΡΠΊΠ΅ ΠΏΠ΅ΡΠ΅Ρ
ΠΎΠ΄Π° G1/S ΡΠ°Π· CDK4, CDK6 ΠΈ CYCLIN-D1, Π°Π½ΡΠΈΠ°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ² MDM2, MDM4, ΠCL2 ΠΈ MCL1, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΠΠ-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π· DNMT3A ΠΈ DNMT3B ΠΈ Π΄ΡΡΠ³ΠΈΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ». ΠΠΏΠΈΡΠ°Π½ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΎΠ±ΡΠ°ΡΠ½ΡΡ
ΡΠ²ΡΠ·Π΅ΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Ρ53 ΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠΌΠΈ ΠΈΠΌ ΠΌΠΈΠΊΡΠΎΠ ΠΠ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΎΡΡΠΈΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ
ΠΎΠ±ΡΠ°ΡΠ½ΡΡ
ΡΠ²ΡΠ·Π΅ΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΠΌΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ c-MYC ΠΈ ΠΠΠ-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·Π°ΠΌΠΈ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°Π½Π½ΡΠ΅, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠ΅ Π² ΠΎΠ±Π·ΠΎΡΠ΅, ΡΡΠΎΡΠ½ΡΡΡ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΡ ΠΎ ΡΠ°Π±ΠΎΡΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠΉ ΡΠ΅ΡΠΈ Π±Π΅Π»ΠΊΠ° Ρ53 ΠΈ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΡ
ΠΈΠΌ ΠΌΠΈΠΊΡΠΎΠ ΠΠ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ΄ΡΠ΅ΡΠΊΠΈΠ²Π°ΡΡ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΡ Ρ53-ΡΠ΅ΡΠΏΠΎΠ½Π·ΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ
ΠΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΏΡΠΈ Π΄ΠΈΡΡΡΠ·Π½ΠΎΠΉ Π-ΠΊΡΡΠΏΠ½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΌΠ΅
Introduction. A more in-depth description of molecular events that disrupt the functioning of the p53 signaling pathway is important for understanding the mechanisms of formation and progression of diffuse B-large cell lymphoma (DCCL), as well as its sensitivity to treatment. The p53 protein exhibits its oncosuppressive function and mediates the antitumor effects of drugs by regulating transcription and/or maturation of a wide range of target genes, including MIR-34A, MIR34B/C, MIR-129-2 and MIR-203. In the tumor tissue of lymphomas, in comparison with normal lymphoid tissue, a decrease in the level of microRNAs encoded by these genes is shown.Aim. The aim of this study was to conduct a comprehensive analysis of the methylation of the genes of the p53-responsive microRNAs MIR-34A, MIR-34B/C, MIR-203 and MIR-129-2, as well as mutations in the DNA-binding domain and destruction of the polyadenylation signal of the TP53 gene in DLBCL.Materials and methods. 136 DNA samples isolated from tumor tissue of patients with DLBCL and 11 DNA samples obtained from lymph nodes with reactive B-cell follicular hyperplasia were analyzed. The methylation status of MIR-203 and MIR-129-2 genes was determined by the method of methyl-specific polymerase chain reaction, MIR-34A and MIR-34B/C genes by the method of methyl-sensitive analysis of high-resolution melting curves. In tumor samples, rs78378222 genotyping was performed by polymerase chain reaction with restriction fragment length polymorphism, resulting in the destruction of the polyadenylation signal, and the nucleotide sequence of the region of the TP53 gene encoding the DNA-binding domain was determined by capillary direct sequencing by Sanger.Results. The methylation detected in lymphoma tissue was tumor-specific. The frequency of analyzed aberrations in the TP53 gene and methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 was 21, 23, 55, 65 and 66 %, respectively. At the same time, methylation of the analyzed genes of p53-responsive microRNAs and aberrations in the TP53 gene in the tumor tissue of patients with DLBCL were independent events with a tendency to mutual exclusion. At the same time, it was shown that in the vast majority of lymphoma samples, the methylation of the MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes was combined.Conclusion. Along with aberrations in TP53, methylation of MIR-34A, MIR-34B/C, MIR-129-2 and MIR-203 genes may be an important cause of decreased expression of miR-34a, miR-34b, miR-34c, miR-129 and miR-203 in DLBCL. The combined methylation of the MIR-203, MIR-129-2 and MIR-34B/C genes, as well as the MIR-34B/C and MIR-34A pairs, potentially has a more pronounced pro-tumor effect due to the presence of common targets in the microRNAs encoded by them.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄Π»Ρ ΠΏΠΎΠ½ΠΈΠΌΠ°Π½ΠΈΡ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΠΈ Π΄ΠΈΡΡΡΠ·Π½ΠΎΠΉ Π-ΠΊΡΡΠΏΠ½ΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΌΡ (ΠΠΠΠΠ), Π° ΡΠ°ΠΊΠΆΠ΅ Π΅Π΅ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΊ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΈΠΌΠ΅Π΅Ρ Π±ΠΎΠ»Π΅Π΅ Π³Π»ΡΠ±ΠΎΠΊΠΎΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΠΎ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΡΠΎΠ±ΡΡΠΈΡΡ
, Π½Π°ΡΡΡΠ°ΡΡΠΈΡ
ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΈ Ρ53. ΠΠ΅Π»ΠΎΠΊ Ρ53 ΠΏΡΠΎΡΠ²Π»ΡΠ΅Ρ ΡΠ²ΠΎΡ ΠΎΠ½ΠΊΠΎΡΡΠΏΡΠ΅ΡΡΠΎΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΡ ΠΈ ΠΎΠΏΠΎΡΡΠ΅Π΄ΡΠ΅Ρ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΠΈ/ΠΈΠ»ΠΈ ΡΠΎΠ·ΡΠ΅Π²Π°Π½ΠΈΡ ΡΠΈΡΠΎΠΊΠΎΠ³ΠΎ ΡΠΏΠ΅ΠΊΡΡΠ° Π³Π΅Π½ΠΎΠ²-ΠΌΠΈΡΠ΅Π½Π΅ΠΉ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ MIR-34A, MIR-34B/C, MIR-129-2 ΠΈ MIR-203. Π ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ Π»ΠΈΠΌΡΠΎΠΌ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π»ΠΈΠΌΡΠΎΠΈΠ΄Π½ΠΎΠΉ ΡΠΊΠ°Π½ΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ
Π΄Π°Π½Π½ΡΠΌΠΈ Π³Π΅Π½Π°ΠΌΠΈ ΠΌΠΈΠΊΡΠΎΠ ΠΠ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ MIR-34Π, MIR-34Π/Π‘, MIR-203 ΠΈ MIR-129-2, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΌΡΡΠ°ΡΠΈΠΉ Π² ΠΠΠ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠ΅ΠΌ Π΄ΠΎΠΌΠ΅Π½Π΅ ΠΈ ΡΠ°Π·ΡΡΡΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠΈΠ³Π½Π°Π»Π° ΠΊ ΠΏΠΎΠ»ΠΈΠ°Π΄Π΅Π½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π° Π’Π 53 ΠΏΡΠΈ ΠΠΠΠΠ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Ρ 136 ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΠΠ, Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΈΠ· ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠΠΠ, ΠΈ 11 ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΠΠ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΈΠ· Π»ΠΈΠΌΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ·Π»ΠΎΠ² Ρ ΡΠ΅Π°ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π-ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ ΡΠΎΠ»Π»ΠΈΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π³ΠΈΠΏΠ΅ΡΠΏΠ»Π°Π·ΠΈΠ΅ΠΉ. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΡΠ°ΡΡΡΠ° ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½ΠΎΠ² MIR-203 ΠΈ MIR-129-2 ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ, Π³Π΅Π½ΠΎΠ² MIR-34Π ΠΈ MIR-34Π/Π‘ β ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»-ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΊΡΠΈΠ²ΡΡ
ΠΏΠ»Π°Π²Π»Π΅Π½ΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½ΠΈΡ. Π ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ ΡΠ΅ΠΏΠ½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ Ρ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠΎΠΌ Π΄Π»ΠΈΠ½ ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΎΠ½Π½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΎ Π³Π΅Π½ΠΎΡΠΈΠΏΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π°ΡΠΈΠ°Π½ΡΠ° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ rs78378222, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΊ ΡΠ°Π·ΡΡΡΠ΅Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»Π° ΠΏΠΎΠ»ΠΈΠ°Π΄Π΅Π½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ, Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΊΠ°ΠΏΠΈΠ»Π»ΡΡΠ½ΠΎΠ³ΠΎ ΠΏΡΡΠΌΠΎΠ³ΠΎ ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ Π‘ΡΠ½Π³Π΅ΡΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠ°ΠΉΠΎΠ½Π° Π³Π΅Π½Π° Π’Π 53, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΠΠ-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠΉ Π΄ΠΎΠΌΠ΅Π½.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ²Π»ΡΠ΅ΠΌΠΎΠ΅ Π² Π»ΠΈΠΌΡΠΎΠΌΠ½ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½ΠΎΡΠΈΠ»ΠΎ ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅p. Π§Π°ΡΡΠΎΡΠ° Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ
Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 ΠΈ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 21, 23, 55, 65 ΠΈ 66 % ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. ΠΡΠΈ ΡΡΠΎΠΌ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ
Π³Π΅Π½ΠΎΠ² Ρ53-ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ Π°Π±Π΅ΡΡΠ°ΡΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠΊΠ°Π½ΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠΠΠ ΡΠ²Π»ΡΠ»ΠΈΡΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΌΠΈ ΡΠΎΠ±ΡΡΠΈΡΠΌΠΈ Ρ ΡΠ΅Π½Π΄Π΅Π½ΡΠΈΠ΅ΠΉ ΠΊ Π²Π·Π°ΠΈΠΌΠ½ΠΎΠΌΡ ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΈΡ. ΠΠΌΠ΅ΡΡΠ΅ Ρ ΡΠ΅ΠΌ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π² ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡΠ΅ΠΌ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²Π΅ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π»ΠΈΠΌΡΠΎΠΌΡ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 Π½ΠΎΡΠΈΠ»ΠΎ ΡΠΎΡΠ΅ΡΠ°Π½Π½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°ΡΡΠ΄Ρ Ρ Π°Π±Π΅ΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π’Π 53, ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34Π, MIR-34Π/Π‘, MIR-129-2 ΠΈ MIR-203 ΠΌΠΎΠΆΠ΅Ρ ΡΠ²Π»ΡΡΡΡΡ ΡΠ°ΡΡΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ miR-34a, miR-34b, miR-34c, miR-129 ΠΈ miR-203 ΠΏΡΠΈ ΠΠΠΠΠ. Π‘ΠΎΡΠ΅ΡΠ°Π½Π½ΠΎΠ΅ ΠΌΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-203, MIR-129-2 ΠΈ MIR-34B/C, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΠ°ΡΡ MIR-34B/C ΠΈ MIR-34A ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΠΈΠΌΠ΅Π΅Ρ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΉ ΠΏΡΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π·Π° ΡΡΠ΅Ρ Π½Π°Π»ΠΈΡΠΈΡ Ρ ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ
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