154 research outputs found

    Evaluation of indicators of entrepreneurial potential in 2018

    Get PDF
    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

    Get PDF
    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

    Get PDF
    Unified approaches to ensuring the chain of survival can improve the patient’s 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

    ВСхнологичСскиС Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ очистки ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½Ρ‹Ρ… Π²ΠΎΠ΄ ΠΎΡ‚ растворСнных Π½Π΅Ρ„Ρ‚Π΅ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚ΠΎΠ²

    Get PDF
    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.ΠŸΡ€ΠΈΠΎΡ€ΠΈΡ‚Π΅Ρ‚ΠΎΠΌ Π² нСфтяной ΠΏΡ€ΠΎΠΌΡ‹ΡˆΠ»Π΅Π½Π½ΠΎΡΡ‚ΠΈ являСтся сниТСниС Ρ‚Π΅Ρ…Π½ΠΎΠ³Π΅Π½Π½ΠΎΠΉ Π½Π°Π³Ρ€ΡƒΠ·ΠΊΠΈ Π½Π° ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Ρ‹ ΠΎΠΊΡ€ΡƒΠΆΠ°ΡŽΡ‰Π΅ΠΉ срСды. Π‘ΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Ρ‹Π΅ Ρ‚Π΅Ρ…Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡŽΡ‚ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π½Π΅Π³Π°Ρ‚ΠΈΠ²Π½ΠΎΠ΅ воздСйствиС Π½Π° Π²ΠΎΠ΄Π½Ρ‹Π΅ ΠΎΠ±ΡŠΠ΅ΠΊΡ‚Ρ‹, Π³Ρ€ΡƒΠ½Ρ‚Ρ‹, Ρ€Π°ΡΡ‚ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ΠΈ Ρ‚.Π΄. Однако Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠ° эффСктивных тСхничСских Ρ€Π΅ΡˆΠ΅Π½ΠΈΠΉ, Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½Ρ‹Ρ… Π½Π° очистку ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½Ρ‹Ρ… Π²ΠΎΠ΄ ΠΎΡ‚ Π½Π΅Ρ„Ρ‚Π΅ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚ΠΎΠ², продолТаСтся. Π‘ΡƒΡ‰Π΅ΡΡ‚Π²ΡƒΡŽΡ‚ мСханичСскиС, Ρ„ΠΈΠ·ΠΈΠΊΠΎ-химичСскиС ΠΈ биологичСскиС ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹ Π±ΠΎΡ€ΡŒΠ±Ρ‹ с нСфтяным загрязнСниСм. ΠšΠ°ΠΆΠ΄Ρ‹ΠΉ ΠΌΠ΅Ρ‚ΠΎΠ΄ ΠΈΠΌΠ΅Π΅Ρ‚ прСимущСства ΠΈ ограничСния, ΠΌΠΎΠΆΠ΅Ρ‚ Π±Ρ‹Ρ‚ΡŒ использован Π² Ρ€Π°Π·Π½Ρ‹Ρ… ситуациях. ΠŸΡ€Π΅Π΄Π»ΠΎΠΆΠ΅Π½Π° тСхнология очистки ΠΏΠΎΠ΄Π·Π΅ΠΌΠ½Ρ‹Ρ… Π²ΠΎΠ΄ Π½Π° основС биотСхнологичСского ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΈ Π΄ΠΎΠ·ΠΈΡ€ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΏΠΎΠ΄Π°Ρ‡ΠΈ кислорода. Π Π΅ΠΊΠΎΠΌΠ΅Π½Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ΅ Ρ€Π΅ΡˆΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠΆΠ΅Ρ‚ Π±Ρ‹Ρ‚ΡŒ использовано ΠΊΠ°ΠΊ ΡΠ°ΠΌΠΎΡΡ‚ΠΎΡΡ‚Π΅Π»ΡŒΠ½ΠΎΠ΅ ΠΏΡ€ΠΈΡ€ΠΎΠ΄ΠΎΠΎΡ…Ρ€Π°Π½Π½ΠΎΠ΅ мСроприятиС, Ρ‚Π°ΠΊ ΠΈ Π² Π΄ΠΎΠΏΠΎΠ»Π½Π΅Π½ΠΈΠ΅ ΠΊ ΡΡƒΡ‰Π΅ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΌ

    FRUIT AND BERRY CROPS IN THE ENVIRONMENTS OF THE BUZULUKSKY BOR NATIONAL PARK

    Get PDF
    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

    Get PDF
    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

    ΠœΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² Ρ€53-рСспонзивных онкосупрСссорных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΏΡ€ΠΈ гСмобластозах

    Get PDF
    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 – highly conserved small RNA molecules that affect gene expression mainly by suppressing translation. МicroRNAs 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.ЦСль исслСдования – ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²ΠΈΡ‚ΡŒ соврСмСнныС Π΄Π°Π½Π½Ρ‹Π΅ ΠΎ частотС ΠΈ Π·Π½Π°Ρ‡Π΅Π½ΠΈΠΈ мСтилирования Π³Π΅Π½ΠΎΠ² ряда Ρ€53-рСспонзивных онкосупрСссорных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΏΡ€ΠΈ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… заболСваниях систСмы ΠΊΡ€ΠΎΠ²ΠΈ.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π» ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. ΠŸΡ€ΠΎΠ²Π΅Π΄Π΅Π½ поиск доступных Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹Ρ… источников, ΠΎΠΏΡƒΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½Ρ‹Ρ… Π² Π±Π°Π·Π°Ρ… Π΄Π°Π½Π½Ρ‹Ρ… Pubmed ΠΈ РИНЦ. НайдСно 399 статСй, ΠΈΠ· ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… 62 Π±Ρ‹Π»ΠΈ Π²ΠΊΠ»ΡŽΡ‡Π΅Π½Ρ‹ Π² Π΄Π°Π½Π½Ρ‹ΠΉ ΠΎΠ±Π·ΠΎΡ€.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹. Π‘Π΅Π»ΠΎΠΊ Ρ€53 Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΡƒΠ΅Ρ‚ Ρ†Π΅Π»Ρ‹ΠΉ класс ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš – высококонсСрвативных ΠΌΠ°Π»Ρ‹Ρ… ΠΌΠΎΠ»Π΅ΠΊΡƒΠ» РНК, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ Π²Π»ΠΈΡΡŽΡ‚ Π½Π° ΡΠΊΡΠΏΡ€Π΅ΡΡΠΈΡŽ Π³Π΅Π½ΠΎΠ² Π² основном ΠΏΡƒΡ‚Π΅ΠΌ подавлСния трансляции. ΠœΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΈΠ³Ρ€Π°ΡŽΡ‚ Π²Π°ΠΆΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π²ΠΎ всСх ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½Ρ‹Ρ… процСссах ΠΈ ΠΌΠΎΠ³ΡƒΡ‚ ΠΈΠΌΠ΅Ρ‚ΡŒ ΠΊΠ°ΠΊ онкосупрСссорныС, Ρ‚Π°ΠΊ ΠΈ ΠΏΡ€ΠΎΠΎΠ½ΠΊΠΎΠ³Π΅Π½Π½Ρ‹Π΅ свойства. ΠΠ°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ экспрСссии Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… Ρ€53 онкосупрСссорных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš Π² Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… опухолях ΠΌΠΎΠ³ΡƒΡ‚ Π±Ρ‹Ρ‚ΡŒ связаны со спСцифичСскими эпигСнСтичСскими ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ (ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π”ΠΠš ΠΈ Π΄Π΅Π°Ρ†Π΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ гистонов). Π’ ΠΎΠ±Π·ΠΎΡ€Π΅ рассмотрСны молСкулярно-гСнСтичСскиС характСристики онкосупрСссорных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš, Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… ΠΏΡ€ΠΈ Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½ΠΎΠΌ ΠΊΡ€ΠΎΠ²Π΅Ρ‚Π²ΠΎΡ€Π΅Π½ΠΈΠΈ, Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΠ΅ экспрСссии ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΡ€ΠΈ Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠΈ гСмобластозов, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: miR-34a, miR-34b/с, miR-145, miR-143 ΠΈ miR-203. Π˜Π·Π²Π΅ΡΡ‚Π½ΠΎ, Ρ‡Ρ‚ΠΎ транскрипция Π³Π΅Π½ΠΎΠ² этих ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš осущСствляСтся ΠΈ рСгулируСтся с собствСнных ΠΏΡ€ΠΎΠΌΠΎΡ‚ΠΎΡ€ΠΎΠ². ΠŸΡ€ΠΈΠ²Π΅Π΄Π΅Π½Ρ‹ послСдниС ΠΎΠΏΡƒΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Π½Ρ‹Π΅ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ исслСдований ΠΏΠΎ диагностичСскому, прогностичСскому ΠΈ клиничСскому Π·Π½Π°Ρ‡Π΅Π½ΠΈΡŽ мСтилирования Π³Π΅Π½ΠΎΠ² рассматриваСмых ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΏΡ€ΠΈ злокачСствСнных новообразованиях систСмы ΠΊΡ€ΠΎΠ²ΠΈ. Богласно Π΄Π°Π½Π½Ρ‹ΠΌ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹Ρ… источников, частыми ΠΎΠ±Ρ‰ΠΈΠΌΠΈ мишСнями для ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš miR-34a, miR-34b/с, miR-145, miR-143 ΠΈ miR-203 ΡΠ²Π»ΡΡŽΡ‚ΡΡ ΠΌ-РНК ряда ΠΏΡ€ΠΎΠΎΠ½ΠΎΠΊΠΎΠ³Π΅Π½ΠΎΠ², Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: транскрипционного Ρ„Π°ΠΊΡ‚ΠΎΡ€Π° C-MYC, ΠΏΠΎΠ·ΠΈΡ‚ΠΈΠ²Π½Ρ‹Ρ… рСгуляторов ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ³ΠΎ Ρ†ΠΈΠΊΠ»Π° Π² ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½ΠΎΠΉ Ρ‚ΠΎΡ‡ΠΊΠ΅ ΠΏΠ΅Ρ€Π΅Ρ…ΠΎΠ΄Π° G1/S Ρ„Π°Π· CDK4, CDK6 ΠΈ CYCLIN-D1, антиапоптотичСских Π±Π΅Π»ΠΊΠΎΠ² MDM2, MDM4, Π’CL2 ΠΈ MCL1, Π° Ρ‚Π°ΠΊΠΆΠ΅ Π”ΠΠš-мСтилтрансфСраз DNMT3A ΠΈ DNMT3B ΠΈ Π΄Ρ€ΡƒΠ³ΠΈΡ… ΠΌΠΎΠ»Π΅ΠΊΡƒΠ». Описано Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹Ρ… ΠΎΠ±Ρ€Π°Ρ‚Π½Ρ‹Ρ… связСй ΠΌΠ΅ΠΆΠ΄Ρƒ Ρ€53 ΠΈ Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅ΠΌΡ‹ΠΌΠΈ ΠΈΠΌ ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΎΡ‚Ρ€ΠΈΡ†Π°Ρ‚Π΅Π»ΡŒΠ½Ρ‹Ρ… ΠΎΠ±Ρ€Π°Ρ‚Π½Ρ‹Ρ… связСй ΠΌΠ΅ΠΆΠ΄Ρƒ Ρ€53-рСспонзивными ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΈ c-MYC ΠΈ Π”ΠΠš-мСтилтрансфСразами.Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅. Π”Π°Π½Π½Ρ‹Π΅, прСдставлСнныС Π² ΠΎΠ±Π·ΠΎΡ€Π΅, ΡƒΡ‚ΠΎΡ‡Π½ΡΡŽΡ‚ соврСмСнныС прСдставлСния ΠΎ Ρ€Π°Π±ΠΎΡ‚Π΅ рСгуляторной сСти Π±Π΅Π»ΠΊΠ° Ρ€53 ΠΈ Π°ΠΊΡ‚ΠΈΠ²ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… ΠΈΠΌ ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΏΠΎΠ΄Ρ‡Π΅Ρ€ΠΊΠΈΠ²Π°ΡŽΡ‚ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΡƒΡŽ Π°ΡΡΠΎΡ†ΠΈΠ°Ρ†ΠΈΡŽ Ρ€53-рСспонзивных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš

    ΠœΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡ‹ Π½Π°Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ экспрСссии Π³Π΅Π½ΠΎΠ² Ρ€53-рСспонсивных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΏΡ€ΠΈ Π΄ΠΈΡ„Ρ„ΡƒΠ·Π½ΠΎΠΉ Π’-ΠΊΡ€ΡƒΠΏΠ½ΠΎΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π»ΠΈΠΌΡ„ΠΎΠΌΠ΅

    Get PDF
    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.Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅. Π‘ΠΎΠ»ΡŒΡˆΠΎΠ΅ Π·Π½Π°Ρ‡Π΅Π½ΠΈΠ΅ для понимания ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² формирования ΠΈ прогрСссии Π΄ΠΈΡ„Ρ„ΡƒΠ·Π½ΠΎΠΉ Π’-ΠΊΡ€ΡƒΠΏΠ½ΠΎΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π»ΠΈΠΌΡ„ΠΎΠΌΡ‹ (Π”Π’ΠšΠšΠ›), Π° Ρ‚Π°ΠΊΠΆΠ΅ Π΅Π΅ Ρ‡ΡƒΠ²ΡΡ‚Π²ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ ΠΊ Π»Π΅Ρ‡Π΅Π½ΠΈΡŽ ΠΈΠΌΠ΅Π΅Ρ‚ Π±ΠΎΠ»Π΅Π΅ Π³Π»ΡƒΠ±ΠΎΠΊΠΎΠ΅ прСдставлСниС ΠΎ молСкулярных событиях, Π½Π°Ρ€ΡƒΡˆΠ°ΡŽΡ‰ΠΈΡ… Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ сигнального ΠΏΡƒΡ‚ΠΈ Ρ€53. Π‘Π΅Π»ΠΎΠΊ Ρ€53 проявляСт свою ΠΎΠ½ΠΊΠΎΡΡƒΠΏΡ€Π΅ΡΡΠΎΡ€Π½ΡƒΡŽ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΡŽ ΠΈ опосрСдуСт ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Π΅ эффСкты лСкарствСнных ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ΠΎΠ² посрСдством рСгуляции транскрипции ΠΈ/ΠΈΠ»ΠΈ созрСвания ΡˆΠΈΡ€ΠΎΠΊΠΎΠ³ΠΎ спСктра Π³Π΅Π½ΠΎΠ²-мишСнСй, Π² Ρ‚ΠΎΠΌ числС MIR-34A, MIR-34B/C, MIR-129-2 ΠΈ MIR-203. Π’ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠΉ Ρ‚ΠΊΠ°Π½ΠΈ Π»ΠΈΠΌΡ„ΠΎΠΌ ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с Π½ΠΎΡ€ΠΌΠ°Π»ΡŒΠ½ΠΎΠΉ Π»ΠΈΠΌΡ„ΠΎΠΈΠ΄Π½ΠΎΠΉ Ρ‚ΠΊΠ°Π½ΡŒΡŽ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ сниТСниС уровня ΠΊΠΎΠ΄ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… Π΄Π°Π½Π½Ρ‹ΠΌΠΈ Π³Π΅Π½Π°ΠΌΠΈ ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš.ЦСль исслСдования – комплСксный Π°Π½Π°Π»ΠΈΠ· мСтилирования Π³Π΅Π½ΠΎΠ² Ρ€53-рСспонсивных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš MIR-34А, MIR-34Π’/Π‘, MIR-203 ΠΈ MIR-129-2, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΉ Π² Π”ΠΠš-ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰Π΅ΠΌ Π΄ΠΎΠΌΠ΅Π½Π΅ ΠΈ Ρ€Π°Π·Ρ€ΡƒΡˆΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ сигнала ΠΊ ΠΏΠΎΠ»ΠΈΠ°Π΄Π΅Π½ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΡŽ Π³Π΅Π½Π° Π’Π 53 ΠΏΡ€ΠΈ Π”Π’ΠšΠšΠ›.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. ΠŸΡ€ΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Ρ‹ 136 ΠΎΠ±Ρ€Π°Π·Ρ†ΠΎΠ² Π”ΠΠš, Π²Ρ‹Π΄Π΅Π»Π΅Π½Π½ΠΎΠΉ ΠΈΠ· ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠΉ Ρ‚ΠΊΠ°Π½ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π”Π’ΠšΠšΠ›, ΠΈ 11 ΠΎΠ±Ρ€Π°Π·Ρ†ΠΎΠ² Π”ΠΠš, ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½ΠΎΠΉ ΠΈΠ· лимфатичСских ΡƒΠ·Π»ΠΎΠ² с Ρ€Π΅Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΉ Π’-ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ фолликулярной Π³ΠΈΠΏΠ΅Ρ€ΠΏΠ»Π°Π·ΠΈΠ΅ΠΉ. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ статуса мСтилирования Π³Π΅Π½ΠΎΠ² MIR-203 ΠΈ MIR-129-2 осущСствляли ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΌΠ΅Ρ‚ΠΈΠ»-спСцифичной ΠΏΠΎΠ»ΠΈΠΌΠ΅Ρ€Π°Π·Π½ΠΎΠΉ Ρ†Π΅ΠΏΠ½ΠΎΠΉ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ, Π³Π΅Π½ΠΎΠ² MIR-34А ΠΈ MIR-34Π’/Π‘ – ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΌΠ΅Ρ‚ΠΈΠ»-Ρ‡ΡƒΠ²ΡΡ‚Π²ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° ΠΊΡ€ΠΈΠ²Ρ‹Ρ… плавлСния высокого Ρ€Π°Π·Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ. Π’ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹Ρ… ΠΎΠ±Ρ€Π°Π·Ρ†Π°Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»ΠΈΠΌΠ΅Ρ€Π°Π·Π½ΠΎΠΉ Ρ†Π΅ΠΏΠ½ΠΎΠΉ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ с ΠΏΠΎΠ»ΠΈΠΌΠΎΡ€Ρ„ΠΈΠ·ΠΌΠΎΠΌ Π΄Π»ΠΈΠ½ рСстрикционных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π²Ρ‹ΠΏΠΎΠ»Π½Π΅Π½ΠΎ Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Π° Π½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ rs78378222, приводящСго ΠΊ Ρ€Π°Π·Ρ€ΡƒΡˆΠ΅Π½ΠΈΡŽ сигнала полиадСнилирования, с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ капиллярного прямого сСквСнирования ΠΏΠΎ БэнгСру ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π° нуклСотидная ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ Ρ€Π°ΠΉΠΎΠ½Π° Π³Π΅Π½Π° Π’Π 53, ΠΊΠΎΠ΄ΠΈΡ€ΡƒΡŽΡ‰Π΅Π³ΠΎ Π”ΠΠš-ΡΠ²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰ΠΈΠΉ Π΄ΠΎΠΌΠ΅Π½.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹. ВыявляСмоС Π² Π»ΠΈΠΌΡ„ΠΎΠΌΠ½ΠΎΠΉ Ρ‚ΠΊΠ°Π½ΠΈ ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ носило опухолСспСцифичный Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅p. Частота Π°Π½Π°Π»ΠΈΠ·ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… Π°Π±Π΅Ρ€Ρ€Π°Ρ†ΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 ΠΈ мСтилирования MIR-34А, MIR-34Π’/Π‘, MIR-129-2 ΠΈ MIR-203 составила 21, 23, 55, 65 ΠΈ 66 % соотвСтствСнно. ΠŸΡ€ΠΈ этом ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π½Π°Π»ΠΈΠ·ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… Π³Π΅Π½ΠΎΠ² Ρ€53-рСспонсивных ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΈ Π°Π±Π΅Ρ€Ρ€Π°Ρ†ΠΈΠΉ Π² Π³Π΅Π½Π΅ Π’Π 53 Π² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²ΠΎΠΉ Ρ‚ΠΊΠ°Π½ΠΈ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π”Π’ΠšΠšΠ› являлись нСзависимыми событиями с Ρ‚Π΅Π½Π΄Π΅Π½Ρ†ΠΈΠ΅ΠΉ ΠΊ Π²Π·Π°ΠΈΠΌΠ½ΠΎΠΌΡƒ ΠΈΡΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΡŽ. ВмСстС с Ρ‚Π΅ΠΌ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, Ρ‡Ρ‚ΠΎ Π² ΠΏΠΎΠ΄Π°Π²Π»ΡΡŽΡ‰Π΅ΠΌ Π±ΠΎΠ»ΡŒΡˆΠΈΠ½ΡΡ‚Π²Π΅ ΠΎΠ±Ρ€Π°Π·Ρ†ΠΎΠ² Π»ΠΈΠΌΡ„ΠΎΠΌΡ‹ ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34А, MIR-34Π’/Π‘, MIR-129-2 ΠΈ MIR-203 носило сочСтанный Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€.Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅. Наряду с абСррациями Π² Π’Π 53, ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-34А, MIR-34Π’/Π‘, MIR-129-2 ΠΈ MIR-203 ΠΌΠΎΠΆΠ΅Ρ‚ ΡΠ²Π»ΡΡ‚ΡŒΡΡ частой ΠΏΡ€ΠΈΡ‡ΠΈΠ½ΠΎΠΉ сниТСния экспрСссии miR-34a, miR-34b, miR-34c, miR-129 ΠΈ miR-203 ΠΏΡ€ΠΈ Π”Π’ΠšΠšΠ›. Π‘ΠΎΡ‡Π΅Ρ‚Π°Π½Π½ΠΎΠ΅ ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Π³Π΅Π½ΠΎΠ² MIR-203, MIR-129-2 ΠΈ MIR-34B/C, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΏΠ°Ρ€Ρ‹ MIR-34B/C ΠΈ MIR-34A ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½ΠΎ ΠΈΠΌΠ΅Π΅Ρ‚ Π±ΠΎΠ»Π΅Π΅ Π²Ρ‹Ρ€Π°ΠΆΠ΅Π½Π½Ρ‹ΠΉ ΠΏΡ€ΠΎΠΎΠΏΡƒΡ…ΠΎΠ»Π΅Π²Ρ‹ΠΉ эффСкт Π·Π° счСт наличия Ρƒ ΠΊΠΎΠ΄ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… ΠΈΠΌΠΈ ΠΌΠΈΠΊΡ€ΠΎΠ ΠΠš ΠΎΠ±Ρ‰ΠΈΡ… мишСнСй
    • …
    corecore