bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Mushroom Pleurotus tuber-regium (Rumph. ex) Fr. Extract on Lipid Profile and Testosterone of Rat
Authors: Danadapat Sukumar , Kumar Manoj , Ranjan Rakesh , Sinha Manoranjan Prasad
Published: November 2020

Pleurotus tuber-regium has been used as fodder and traditionally used as medicinal supplement. The aim of this study was to screen in vitro proximate biochemical composition and nutritional potentiality of P. tuber-regium extract for further in vivo analysis of impact of the extract on serum lipid and testosterone profile of rats. Total cholesterol, HDL cholesterol, LDL cholesterol were measured photometrically. Testosterone was measured by chemiluminescence immune assay. P. tuber-regium extract contains different biochemicals such as proteins, carbohydrates, tannins, flavonoids, phenols etc. and showed highly quantified calorific value (297.89±1.92 calori/100g). Acute toxicity test showed no mortality and toxic behavioural symptoms. Significant decrease in total cholesterol (75.52±0.39mg/dL), LDL cholesterol (34.58±1.69mg/dL) and triglyceride (81.31±1.25) were observed in rat group treated with 200mg/kg dose of extract. 400mg/kg dose of extract showed higher efficacy than 200mg/kg dose of extract and significantly decreased total cholesterol (72.25±1.11mg/dL), LDL cholesterol (26.37±1.21mg/dL) and triglyceride (69.42±0.72). The extract showed testosterone enhance efficacy. 400mg/kg dose of extract showed high level testosterone (178.96±0.68 ng/dL) enhance efficacy than 200mg/kg dose (174.64±0.64ng/dL). Due to hypocholesterolaemia and testosterone elevating properties of P. tuber-regium extract, it can be said that, mushroom P. tuber-regium can be consumed as healthy diet supplement to maintain cholesterol level and to maintain good male reproductive health.
EU regulation in the area of acceptance and execution of court decisions in civil and business cases rendered in the EU member-states in the Republic of Bulgaria
Authors: Dimitrov Nikolay Svetlozarov
Published: November 2020

The subject of this research is the international legal acts in the area of acceptance and execution of decisions rendered by foreign courts, current procedural legislation of the Republic of Bulgaria, as well as research publications on this topic. The object of this research is the legal foundation and procedural actions in acceptance and execution of foreign court decisions on civil and commercial issues in the Republic of Bulgaria. The author carefully examines the rules directly related to execution and refusal to execute a court decision rendered in a member-state on the territory of Bulgaria. Special attention is given to the multiple issues pertaining to implementation of EU regulations recently passed in the area of EU civil process. Analysis of the positions dedicated to direct execution and refusal to execute a court decision is conducted in the context of the position of Brussels I Bis Regulation. The author makes following conclusions and recommendations: Bulgarian legislator needs to eliminate the difference between obligation to execute a foreign court decision and domestic court decision; it is necessary to amend the Civil Procedure Code of Bulgaria, as well as clarify the process of refusal to execute in accordance with the Article 47 of the Brussels I Bis Regulation. The author’s contribution into the research of this topic consists in the recommendation on improvements to the legal regulation and passing equal conditions for execution of foreign and national court decisions within the framework of the EU.
Goals of the United Nations strategic development and international protection from disaster: correlation and implementation
Authors: Lisauskaite Valentina Vlado
Published: November 2020

The subject of this research is the international relations on accomplishment of sustainable development goals, taking into account the risks of disasters and remedy against them. The object of this research is several documents: United Nations General Assembly Resolutions “Our Changing World: Agenda on Sustainable Development until 2030”, Sendai Framework for Disaster Risk Reduction 2015, Paris Agreement on Climate Change 2015. Detailed analysis is conducted on the provisions of the indicated documents in the context of their interrelation for effective implementation. Special attention is dedicated the impact of disaster risk upon sustainable development goals, namely their accomplishment. The following conclusions were formulated: sustainable development goals represents basic trends for development of each country and global community as  a whole; they are directly related to less significant problems that trying to be resolved by joint efforts of the global community (protection from disasters and climate change). These three block represent the equilateral sides of a triangle of international relations, realized for the purpose of harmonious development of modern civilization. The author’s special contribution lies in correlation of the particular provisions of aforementioned documents, and in schematic interpretation of such correlation. The novelty lies in the fact that the science of international law usually reviews these documents separately from each other, just mentioning their interrelation. The author reflect the approach that is being currently implemented by specific practitioners on elaboration of indicators of interrelation between sustainable development goals and disaster risk reduction.
International legal status of the Arctic Region and its role within modern system of international relations
Authors: Klimanov Nikita Viktorovich , Mazlumyan David Eduardovich
Published: November 2020

This article examines the image of the Arctic Region as a large geopolitical actor with clear division of the zone of political influence of modern countries. The article reviews the negative aspects of lobbying for the interests of separate countries, which impact situation in the region, as well as negative consequences substantiated by the absence of standardized international legislative regulation of security regime and presence of external actors in the region. Within the framework of this study, the authors carried out a legal and economic analysis of the current geopolitical situation, as well as existing aspects of normative regulation of this branch in the region, as well as concluded on the possibility of joint development of the bottom of the Arctic shelf and realization of projects in the sphere of natural resource management of the Arctic Region. The scientific novelty consists in a brief, but in-depth substantiation of typical characteristics of the current system of international relations, as well as in the complex analysis of significance of the Arctic region on the agenda of world politics, and determination of “Arctic policy” as a separate vector in strategy of the leading countries of the world. The authors consider legal characteristics and existing approaches towards determination of legal status of the Arctic territories, which vary in different political-legal traditions. United Nations Convention on the Law of the Sea of 1982 is the framework document that serves as the basis of national justification of claims in the Arctic Region. The main conclusion consists in the description of the existing conflict of laws, which can be overcome successfully only in terms of mutual, joint, fruitful cooperation of the key political actors that are involved or have political aspirations in the Arctic Region.
Relationship between well pattern density and variation function of stochastic modelling and database establishment
Authors: Wang Jinkai , Zhao Kai , Yan Zhaoxun , Fu Yuxiang , Xie Jun
Published: November 2020

For 3D geological modelling of oil and gas reservoirs, well pattern density is directly related to the number of samples involved in the calculation, which determines the variation function of stochastic modelling and has great impacts on the results of reservoir modelling. This paper focuses on the relationship between well pattern density and the variogram of stochastic modelling, selects the large Sulige gas field with many well pattern types as the research object, and establishes a variogram database of stochastic models for different well pattern densities. First, the well pattern in the study area is divided into three different types (well patterns A, B, and C) according to well and row space. Several different small blocks (model samples) are selected from each type of well pattern to establish the model, and their reasonable variogram values (major range, minor range and vertical range) are obtained. Then, the variogram values of all model samples with similar well pattern densities are analysed and counted, and the variogram database corresponding to each type of well pattern is established. Finally, the statistical results are applied to the modelling process of other blocks with similar well pattern density to test their accuracy. The results show that the reservoir model established by using the variation function provided in this paper agrees well with the actual geological conditions and that the random model has a high degree of convergence. This database has high adaptability, and the model established is reliable.
Anti-nuclear antibodies: A practical approach to testing and interpretation
Authors: Santhosh Parvathy , Ajithkumar Kidangazhiathmana
Published: November 2020

Anti-nuclear antibodies (ANAs) are a group of antibodies that are characteristically associated with connective tissue diseases (CTDs). Indirect immunofluorescence antibody technique, having a high sensitivity, is the most common technique used for detection, results of which are expressed in terms of the pattern of fluorescence, substrate used, and the titer of a positive test. Other methods include solid-phase assays. ANA test must be performed only when there is a clinical suspicion of an autoimmune CTD. ANA should not be used as a screening tool for asymptomatic individuals. It is essential in clinical practice to be aware of when to order ANA testing, and how to correctly interpret the test results.
Successful treatment of superior sagittal sinus thrombosis after translabyrinthine resection of metastatic neuroendocrine tumor: A case report and review of literature
Authors: Wong Andrew K. , Wong Ricky H.
Published: November 2020

Background:

Postoperative cerebral venous sinus thrombosis (pCVST) after resection of cerebellopontine angle and posterior fossa tumor resections occur almost exclusively in the lateral venous sinuses and are generally asymptomatic. Thrombus extension and involvement of the superior sagittal sinus (SSS) – a serious and potentially devastating complication – are rarely described and, as such, successful treatment for which is still poorly understood. We report a case of pCVST involving the SSS after translabyrinthine approach for resection of a metastatic neuroendocrine tumor (NET), and the first that was successfully treated with anticoagulation therapy.

Case Description:

A 40-year-old man presented with headaches, diminished right-sided hearing, and ataxia was found to have a large right-sided cerebellopontine angle (CPA) lesion with extra-axial and possible intraparenchymal invasion. A retrosigmoid craniotomy for debulking and diagnosis was undertaken. Postoperative imaging revealed patent venous sinuses. Pathology confirmed NET. Further imaging revealed a likely pancreatic primary lesion. The patient then underwent subsequent translabyrinthine approach for definitive surgical resection. Postoperative imaging again revealed patent venous sinuses. The patient subsequently developed headaches on postoperative day 10 and was found to have pCVST involving the ipsilateral internal jugular to the SSS. The patient was started on therapeutic heparin with significant improvement in pCVST and symptoms.

Conclusion:

Extensive pCVST involving the SSS after CPA and posterior fossa tumor resections is extremely rare. Initial management with anticoagulation can yield promising results and should be initiated early in the clinical course unless otherwise contraindicated.
Prolonged length of stay and discharge disposition to rehabilitation facilities following single-level posterior lumbar interbody fusion for acquired spondylolisthesis
Authors: Benton Joshua Alexander , Ramos Rafael De La Garza , Gelfand Yaroslav , Krystal Jonathan D. , Yanamadala Vijay , Yassari Reza , Kinon Merritt D.
Published: November 2020

Background:

Acquired lumbar spondylolisthesis is often treated with interbody fusion. However, few studies have evaluated predictors for prolonged length of stay (LOS) and disposition to rehabilitation facilities after posterior single-level lumbar interbody fusion for acquired spondylolisthesis.

Methods:

The American College of Surgeons National Quality Improvement Program database was queried for adults with acquired spondylolisthesis who underwent single-level lumbar interbody fusion through a posterior approach (posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion [TLIF]). We utilized multivariate logistic regression analysis to identify predictors of prolonged LOS and disposition in this patient population.

Results:

Among 2080 patients identified, 700 (33.7%) had a prolonged LOS (≥4 days), and 306 (14.7%) were discharged postoperatively to rehabilitation facilities. Predictors for prolonged LOS included: American Society of Anesthesiologist (ASA) class ≥3, anemia, prolonged operative time, perioperative blood transfusion, pneumonia, urinary tract infections, and return to the operating room. The following risk factors predicted discharge to postoperative rehabilitation facilities: age ≥65 years, male sex, ASA class ≥3, modified frailty score ≥2, perioperative blood transfusion, and prolonged LOS.

Conclusion:

Multiple partial-overlapping risk factors predicted prolonged LOS and discharge to rehabilitation facilities after single-level TLIF/PLIF performed for acquired spondylolisthesis.
BIOAKTIVITAS ASAM JAWA (Tamarindus indica) DAN PEMANFAATANNYA
Authors: Silalahi Marina
Published: November 2020

Tamarindus indica is one of the species in the Fabaceae which is widely used as food and traditional medicine. T. indica has naturalized in Indonesia, especially in Java Island and mostly only used as food, while its use as medicine is still limited. This study aims to explain the relationship between the use of T. indica as a traditional medicine and its bioactivity. The method used in this study is based on literature studies obtained online using the key word Tamarindus indica, uses of T. indica and bioactivities of T. indica. The use of T. indica as a traditional medicine is related to its bioactivity. Bioactivity of T. indica as antimicrobial, antidiabetic mellitus, anti-cholesterol, analgesic, antiobesity and antioxidant. Bioactivity of T. indica as anti-microbial and anti-cancer has the potential to be developed as a food preservative as well as providing healthy effects
Expression of alpha-synuclein gene and genes of lysosomal membrane proteins and enzymes in Parkinson’s disease associated with mutation in the GBA gene
Authors: Усенко Т.С. , Безрукова А.И. , Богданова Д.А. , Сенкевич К.А. , Кудреватых А.В. , Милюхина И.В. , Пчелина С.Н.
Published: November 2020

Мутации в гене, кодирующем лизосомный фермент глюкоцереброзидазу (GBA), являются фактором высокого риска болезни Паркинсона (БП). Остается неясным, почему не у всех носителей мутаций в данном гене в течение жизни развивается БП. Предполагается, что дисфункция мембранных белков и ферментов лизосом может способствовать развитию БП у носителей мутаций в гене GBA. В данном исследовании была оценена экспрессия генов альфа-синуклеина и LAMP2, GLA, GALNS, SCARB2 в CD45+ клетках периферической крови у пациентов с GBA-БП, бессимптомных носителей мутаций в гене GBA (GBA-носителей), а также в у пациентов с БП и в контроле. Выявлена повышенная экспрессия гена альфа-синуклеина на фоне снижения уровня экспрессии генов мембранных белков лизосом (LAMP2, SCARB2) у пациентов с GBA-БП и GBA-носителей, что может свидетельствовать о вовлеченности этих генов в патогенез GBA-БП. Пониженная экспрессия гена LAMP2 может рассматриваться в качестве одного из триггеров развития БП у носителей мутаций в гене GBA.

Mutations in the gene GBA that are encoding the lysosomal enzyme glucocerebrosidase are the most common genetic risk factor for PD. Not every carrier of GBA mutations will develop PD. Probably the dysfunction of lysosomal enzymes and membrane proteins may contribute or protect to the development of PD among carriers of GBA mutations. In the current study LAMP2, GLA, GALNS, SCARB2 and alpha-synuclein mRNA levels in CD45+ blood cells were estimated in patients with GBA-associated PD (GBA-PD), non-manifesting GBA carriers(GBA-Carriers), PD patients and controls. This is the first report estimating LAMP2, GLA, GALNS, SCARB2 and alpha-synuclein expressions in CD45+ blood cells in GBA-PD patients and GBA-Carriers. We revealed increased SNCA expression and changing expression of lysosomal genes (LAMP2, GALNS, SCARB2) that may contribute role these genes in pathogenesis of GBA-PD. Decreased of LAMP2 may be considered as trigger of GBA-PD.
Myotonic dystrophy Rossolimo-Churchman-Steinert-Batten (clinical case)
Authors: Синельникова И.А. , Сопрунова И.В. , Николаева О.П.
Published: November 2020

В статье представлено описание семейного случая миотонической дистрофии Россолимо-Штейнерта-Куршмана-Баттена. Диагноз подтвержден в результате ДНК-диагностики: выявлено увеличенное число копий CTG-повтора гена DMPK, ответственного за развитие миотонической дистрофии.

A family case report of Rossolimo-Steinert-Curschmann myotonic dystrophy is presented. An increased number of copies of CTG-repeats of the DMPK gene responsible for the development of MD, i.e., the diagnosis was confirmed by molecular genetic method.
Using high-throughput sequencing to diagnose causes of cerebral palsy
Authors: Удалова В.Ю. , Канивец И.В. , Пьянков Д.В. , Комарьков И.Ф. , Коростелев С.А.
Published: November 2020

Детский церебральный паралич (ДЦП) - распространенная, клинически гетерогенная группа заболеваний, нарушающих двигательную функцию и поддержание позы. Предполагалось, что генетическую этиологию ДЦП имеют не более чем 2% пациентов. Целью данной работы является определение эффективности высокопроизводительного секвенирования для диагностики причин ДЦП. В нашем исследовании, генетическая этиология установлена у 31,8 % пациентов с ДЦП, возможная причина ДЦП выявлена у 17,5 % пациентов.

Cerebral palsy (CP) is a common, clinically heterogeneous group of disorders affecting movement and posture. It was assumed that the genetic etiology of CP does not exceed 2%. The aim of this work is to determine the effectiveness of high-throughput sequencing for diagnosing the causes of CP. In our study, a genetic etiology was found in 31.8% of patients with CP, a possible cause was identified in 17.5% of patients with CP.
Genetic testing for autistic spectrum disorders
Authors: Померанцева Е.А. , Исаев А.А. , Есакова А.П. , Поволоцкая И.В. , Денисенкова Е.В. , Ветрова Н.В. , Григорьева Ю.О. , Мусатова Е.В.
Published: November 2020

Согласно рекомендациям Американской академии педиатрии при постановке диагноза аутизм, следует направить семью на консультацию генетика и генетическое обследование. Однако оптимальный подход к алгоритму генетического обследования при выявлении расстройства аутистического спектра еще предстоит разработать. В рамках исследования было проведено сравнение выявляемости генетических факторов аутизма различными молекулярно-генетическими тестами.

According to American Academy of Pediatrics recent guidelines, each family with a child diagnosed with autistic spectrum disorder should be reffered to a medical geneticist and offered genetic tests. However, an optimal genetic testing algorithm has yet to be developed. This study was conducted to compare abilities of different molecular-genetic methods to detect genetic factors of autistic spectrum disorders.
Molecular genetic analysis of multiple sclerosis
Authors: Тимашева Я.Р. , Насибуллин Т.Р. , Туктарова И.А. , Эрдман В.В. , Галиуллин Т.Р. , Заплахова О.В. , Бахтиярова К.З. , Мустафина О.Е.
Published: November 2020

Рассеянный склероз - это хроническое воспалительное демиелинизирующее заболевание центральной нервной системы многофакторной природы. Цель настоящего исследования состояла в проведении анализа ассоциаций с заболеванием полиморфных маркеров в генах, продукты которых предположительно участвуют в патогенезе заболевания, а также идентифицированных в результате проведения полногеномных исследований, в популяциях башкир, русских и татар, проживающих в Республике Башкортостан. В результате проведенного исследования нами получены данные, подтверждающие ассоциацию с рассеянным склерозом генов, продукты которых участвуют в развитии аутоиммунного воспаления центральной нервной системы.

Multiple sclerosis is a chronic inflammatory demyelinating disorder of central nervous system of multifactorial origin. Genome-wide association studies identified 700 polymorphic genetic variants associated with multiple sclerosis. The aim of the current study was to analyse associations of the polymorphic markers in genes involved in the pathogenesis of the disease and those identified by genome-wide association studies in the populations of Bashkirs, Russians, and Tatars from the Republic of Bashkortostan (Russian Federation). The study group was comprised of 644 patients with multiple sclerosis and 1408 control group individuals. Genotyping of 35 polymorphic genetic markers was performed using allele-specific PCR and PCR followed by restriction fragment length polymorphism analysis. The data obtained in our study confirm the association with multiple sclerosis of the genes involved in the development of autoimmune inflammation in central nervous system.
New mutations in the integrin-linked kinase gene (ILK) in patients with arrhythmogenic cardiomyopathy
Authors: Сивицкая Л.Н. , Вайханская Т.Г. , Даниленко Н.Г. , Курушко Т.В. , Левданский О.Д. , Ермакович Д.П. , Давыденко О.Г.
Published: November 2020

Представлены два случая аритмогенной правожелудочковой кардиомиопатии (АПЖК) с вовлечением левого желудочка и кожными проявлениями у неродственных пациентов. Методом NGS в обоих случаях выявлены новые варианты в консервативных позициях гена интегрин-связанной киназы (ILK) - p.T181A и p.I188T. Изменения в работе ILK нарушают контакты клеток c матриксом и проведение сигналов, вызывая развитие кардиомиопатий, блистеринг и гиперплазию эпидермиса. С большой вероятностью замены p.T181A и p.I188T являются причиной развития АПЖК и неспецифических кожных проявлений у представленных в статье пациентов, однако требуют дополнительных исследований.

Two cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) with the left ventricle involvement and skin manifestations in unrelated patients are presented in the article. In both cases, new variants in the conserved positions of the integrin-linked kinase gene (ILK), p.T181A and p.I188T, were found using the NGS method. Changes of ILK functioning disrupt cell contact with the matrix and signalling, causing cardiomyopathies development in the heart; blistering and hyperplasia of the epidermis. With a high probability, the substitutions p.T181A and p.I188T result in the ARVC and nonspecific skin manifestations in the patients described in the article. However additional investigations are required.
Mutations in genes associated with inherited arrhythmias in patients with Brugada syndrome
Authors: Чакова Н.Н. , Ниязова С.С. , Комиссарова С.М. , Плащинская Л.И. , Савченко А.А. , Долматович Т.В.
Published: November 2020

Методом высокопроизводительного секвенирования у пациентов с синдромом Бругада проведен поиск мутаций в генах, ассоциированных с наследственными аритмиями. Половина нуклеотидных замен локализована в генах, кодирующих белки натриевых и калиевых ионных каналов (SCN5A, KCNJ2, KCNJ8, HCN4, KCNQ1). Выявлены мутации в генах, ассоциированных преимущественно с другими каналопатиями и аритмогенными кардиомиопатиями.

Mutation detection in the coding sequences of genes associated with inherited arrhythmias was performed by next generation sequencing (NGS) in patients with Brugada syndrome. Half of the mutations are located in the genes encoding the sodium and potassium ion channel proteins (SCN5A, KCNJ2, KCNJ8, HCN4, KCNQ1). In the genes associated predominantly with other canalopathies and arrhythmogenic cardiomyopathies the mutations were found.
Mitochondrial genome variability in sudden cardiac death
Authors: Голубенко М.В. , Салахов Р.Р. , Цепокина А.В. , Афанасьев С.А. , Муслимова Э.Ф. , Реброва Т.Ю. , Арчаков Е.А. , Борисова Е.В. , Баталов Р.Е. , Максимов В.Н. , Иванова А.А. , Гуражева А.А. , Орлов П.С. , Бабушкина Н.П. , Зарубин А.А. , Понасенко А.В. , Назаренко М.С. , Пузырев В.П.
Published: November 2020

Проведено исследование полиморфизма митохондриального генома и числа копий мтДНК в клетке при внезапной сердечной смерти (ВСС). Выявлено более низкое значение числа копий мтДНК в миокарде умерших ВСС. Анализ полиморфизма мтДНК показал более высокую частоту гаплогруппы Н1 в выборке ВСС, по сравнению с популяцией, а также более высокую частоту миссенс-варианта Ala177Thr в гене ATP6 у лиц, переживших остановку сердца. Результаты исследования указывают на связь полиморфизма мтДНК и числа копий мтДНК в клетке с риском внезапной сердечной смерти.

We studied mitochondrial DNA polymorphism and mtDNA copy number in sudden cardiac death (SCD). In the SCD group, a lower mtDNA copy number was found in the myocardium. Analysis of mtDNA polymorphism revealed a higher frequency of H1 haplogroup in the SCD samples, compared with the population, as well as higher frequency of missense variant Ala177Thr in ATP6 gene in the group of cardiac arrest survivors. The results of the study suggest association of mtDNA polymorphism and mtDNA copy number with the risk of sudden cardiac death.
Features of CpG site methylation within miRNA gene MIR10B and transcription factor gene TWIST1 in atherosclerosis
Authors: Марков А.В. , Бабушкина Н.П. , Голубенко М.В. , Салахов Р.Р. , Зарубин А.А. , Слепцов А.А. , Королёва Ю.А. , Шарыш Д.В. , Муслимова Э.Ф. , Афанасьев С.А. , Кузнецов М.С. , Козлов Б.Н. , Назаренко М.С.
Published: November 2020

В работе проведен анализ профилей метилирования гена miR-10b и гена транскрипционного фактора TWIST1, регулирующего экспрессию данной микроРНК, в кровеносных сосудах и лейкоцитах крови пациентов с клинически выраженным атеросклерозом и у относительно здоровых лиц. Обнаружено гипометилирование MIR10B в поражённых атеросклерозом артериях относительно непораженных артерий и вен. Профиль метилирования гена TWIST1 был тканеспецифичен и постоянен вне зависимости от наличия заболевания.

We analyzed DNA methylation profiles within genes of miR-10b and TWIST1 regulating the expression of this microRNA in blood vessels and blood leukocytes of patients with advanced atherosclerosis and in relatively healthy individuals. MIR10B hypomethylation was detected in arteries affected by atherosclerosis in comparison with unaffected arteries and veins. Methylation profile of TWIST1 gene was tissue-specific and consistent regardless of atherosclerosis.
Genetic predictors of early coronary in-stent restenosis
Authors: Богатырева К.Б. , Азова М.М. , Шугушев З.Х. , Аит Аисса А. , Агаджанян А.В. , Цховребова Л.В.
Published: November 2020

В настоящее время рестеноз является основной проблемой, возникающей после чрескожных коронарных вмешательств. К причинам повторного сужения артерии после стентирования относятся клинические, ангиографические и генетические факторы. В представленной работе изучены некоторые полиморфные локусы генов ренин-ангиотензин-альдостероновой системы, фолатного цикла и эндотелиальной синтазы оксида азота. Выявлены генетические варианты, ассоциированные с рестенозом, развивающимся в различные сроки после стентирования (до 6 месяцев или позже).

Currently, restenosis is a major challenge arising after percutaneous coronary interventions. Causes of re-narrowing of the artery after stenting include clinical, angiographic, and genetic factors. Some polymorphic loci of the renin-angiotensin-aldosterone system, folate cycle, and endothelial nitric oxide synthase genes have been studied. Genetic variants associated with the restenosis developing at different time periods after stent implantation (within the first 6 months or later) have been identified.
Epigenetic effects of polymorphism of candidate genes associated with the development of hypertension, according to full-genomic studies
Authors: Абрамова М.Ю.
Published: November 2020

Представлены результаты анализа функциональной значимости полиморфных локусов, ассоциированных с артериальной гипертензией (АГ), по данным каталога GWAS. Функциональные эффекты полиморфных локусов были изучены с использованием онлайн программного обеспечения HaploReg (v4.1), PolyPhen-2, GTEx portal. Для исследования было отобрано 10 SNPs (rs167479, rs8068318, rs7302981, rs4387287, rs932764, rs633185, rs2681472, rs1173771, rs1799945, rs805303), ассоциированных с развитием АГ, по данным не менее чем 3 полногеномных исследований. Установлено, что все полиморфные локусы играют важную функциональную роль: 3 из них являются nsSNPs, 9 имеют связь с экспрессией 74 генов, 5 ассоциированы с уровнем альтернативного сплайсинга транскрипта 69 генов.

This paper presents the results of an analysis of the functional significance of polymorphic loci associated with arterial hypertension, according to the GWAS catalog. Functional effects of polymorphic loci were studied using the online software HaploReg (v4.1), PolyPhen-2, and GTEx portal. The following was selected for the study 10 SNPs (rs167479, rs8068318, rs7302981, rs4387287, rs932764, rs633185, rs2681472, rs1173771, rs1799945, rs805303) associated with the development of arterial hypertension, according to at least 3 full-scale studies. It was found that all polymorphic loci have an important functional role in the body: 3 SNPs are nsSNPs, 9 SNPs are associated with the expression of 74 genes, 5 SNPs are associated with the level of alternative splicing of the transcript of 69 genes.
SNP rs4538 CYP11B2: g.142913286G> T study in essential hypertension
Authors: Тхоренко Б.А. , Цепокина А.В.
Published: November 2020

Обсуждаются результаты анализа последовательности 6 экзона гена CYP11B2 в 40 образцах ДНК пациентов с диагнозом артериальная гипертензия. Выявлена высокая частота мутации в сайте rs4538 (NC_000008.11:g.142913286G>T). Частота носителей аллелей G и Т составила 0,556 и 0,444 соответственно. Уровень содержания альдостерона в сыворотке крови у обследованных в среднем составил 206,1 пг/мл; обнаружена высокая вариация в концентрациях - от 18,18 пг/мл до 933,8 пг/мл. Предварительная оценка ассоциации полиморфизма показала, что при носительстве аллельного варианта Т уровень альдостерона выше (224,0 пг/мл), чем при G (191,7 пг/мл).

The paper presents results of processing sequences of 6th exon CYP11B2 taken from 40 DNA samples of patients diagnosed with arterial hypertension. Site rs4538 (NC_000008.11:g.142913286G>T, NM_000498.3:c.1120C>A) revealed a high mutation frequency. The carrier frequencies of allelic variants G and T were 0.556 and 0.444 respectively. The aldosterone content in the blood serum samples averaged 206.1 pg/ml, with high variation in concentrations ranging from 18.18 pg/ml to 933.8 pg/ml. Preliminary evaluation of polymorphism association showed that aldosterone levels were higher for allele T variant (224.0 pg/ml) than for G (191.7 pg/ml).
Genetic variants of the ITGB3 gene encoding the GP IIIa subunit, and their relationship with quantitative and qualitative characteristics of the platelet receptor for fibrinogen GP IIb-IIIa
Authors: Сироткина О.В. , Масленников А.Б. , Цикаленко Е.А. , Вавилова Т.В. , Пчелина С.Н.
Published: November 2020

В работе представлены результаты исследования генетических вариантов ключевого тромбоцитарного рецептора для фибриногена GPIIb-IIIa, а также взаимосвязь генетических вариантов с количественными характеристиками рецептора и функциональной активностью тромбоцитов.

The results of the study of genetic variants of the key platelet receptor for fibrinogen GPIIb-IIIa, as well as the relationship of genetic variants with quantitative characteristics of the receptor and the functional activity of platelets, were presented.
Application of NGS to improve the effectiveness of molecular genetic diagnostics of monogenic forms of diabetes in children
Authors: Глотов О.С. , Серебрякова Е.А. , Туркунова М.Е. , Башнина Е.Б. , Глотов А.С. , Барбитов Ю.А. , Полев Д.Е. , Иващенко Т.Э. , Федяков М.А. , Сарана А.М. , Щербак С.Г. , Баранов В.С.
Published: November 2020

Исследованы образцы ДНК 60 пациентов с подозрением на наличие моногенного сахарного диабета (МСД-MODY) путем секвенирования NGS панели 13 генов MODY и 22 гена «неонатального» диабета и синдромальных форм диабета. МСД был подтвержден у 55% (n=33). Из 33 пациентов 27 (81,8%) имели мутации (варианты) в MODY генах. Наиболее часто встречались варианты в гене GCK-31,6% (n=19). Спектр вариантов в гене GCK включал 13 миссенс мутаций, 3 нонсенс, 4 со сдвигом рамки считывания и 1 в промоторной области. Были также выявлены варианты в других генах: HNF1A (n=3), WFS1(n=4), PAX4 (n=1), EIF2AK3 (n=1, гомозигота), GATA6 (n=1), KCNJ11(n=1), ABCC8 (n=1), SLC19A2 (n=2), BLK (n=2). Из 38 детектированных вариантов 15 оказались новыми. Высокая выявляемость может быть связана как с особенностями нашей группы, так и с использованным биоинформатическим подходом. Молекулярно-генетическая верификация диагноза при помощи NGS секвенирования позволяет повысить эффективность диагностики, прогнозировать течение заболевания и вносить коррективы в лечение СД.

The present study included 60 unrelated Russian children with non-type 1 diabetes mellitus diagnosed before the age of 18 years. Genetic variants were analyzed using whole-exome sequencing (WES) in a panel of 35 genes causative of maturity onset diabetes of the young (MODY) and transient or permanent neonatal diabetes. Verification of the WES results was performed using PCR-direct sequencing. A total of 38 genetic variants were identified in 33 out of 60 patients (55%). The majority of patients (27/33, 81.8%) had variants in MODY-related genes: GCK (n=19), HNF1A (n=2), PAX4 (n=1), ABCC8 (n=1), KCNJ11 (n=1), GCK+HNF1A (n=1), GCK+BLK (n=1) and GCK+BLK+WFS1 (n=1). A total of 6 patients (6/33, 18.2%) had variants in MODY-unrelated genes: GATA6 (n=1), WFS1 (n=3), EIF2AK3 (n=1) and SLC19A2 (n=1). A total of 15 out of 38 variants were novel, including GCK, HNF1A, BLK, WFS1, EIF2AK3 and SLC19A2. To summarize, the present study demonstrates a high frequency and a wide spectrum of genetic variants causative of monogenic diabetes in Russian children with non-type 1 diabetes mellitus. The spectrum includes previously known and novel variants in MODY-related and unrelated genes, with multiple variants in a number of patients. The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in Russian children may begin with testing for MODY2. However, the remaining variants are present at low frequencies in 9 different genes, altogether amounting to ~50% of the cases and highlighting the efficiency of using WES in non-GCK-MODY cases.
Genes of different molecular classes and their relationship with type 1 diabetes an age of manifestation
Authors: Тарасенко Н.В. , Гончарова И.А. , Марков А.В. , Кондратьева Е.И. , Спирина Л.В. , Саприна Т.В. , Трубченко К.В. , Милованова Т.А. , Пилипенко В.Е. , Назаренко М.С.
Published: November 2020

В работе изучена генетическая составляющая возраста манифестации сахарного диабета 1-го типа (СД1). В общей группе больных СД1 (n=330), а также в подгруппах с разным возрастом манифестации СД1 (до 30 лет, n=269, с 31 года, n=61) и популяционной выборке (n=289) изучено 58 однонуклеотидных полиморфизмов (SNPs), локализованных в 47 генах, продукты которых участвуют в различных метаболических путях и вовлечены в процессы фиброгенеза, эндотелиальную дисфункцию, иммунный ответ и воспаление. Генотипирование выполнено методом масс-спектрометрии на приборе «Sequenom MassARRAY» (США). В результате выявлена ассоциация с возрастом манифестации СД1 до 30 лет rs1007856 гена ITGB5 (генотип TT, р=0,02), rs3765124 гена ADAMDEC1 (генотип AA, р=0,01). При сравнении подгрупп СД1 с разным возрастом манифестации отличия получены для rs1107946 гена COL1A1 (генотип AA, р=0,03) и rs514921 гена MMP1 (генотип AA, р=0,03). Гены, SNPs которых показали ассоциацию с возрастом манифестации СД1, кодируют белковые продукты, вовлеченные в метаболизм экстрацеллюлярного матрикса и коллагена. Данные варианты могут рассматриваться в качестве маркеров возраста дебюта СД1.

We have studied the genetic component of the age of onset of type 1 diabetes (T1D). We examined a group of patients with T1D (n = 330), which was divided into subgroups with different ages of manifestation of T1D (up to 30 years, n = 269, from 31 years old, n=61). A total of 289 healthy population individuals were enrolled in this study. We studied 58 SNPs of 47 genes whose products are involved in various metabolic pathways as well as fibrogenesis, endothelial dysfunction, the immune response and inflammation. We performed genotyping by mass spectrometry using a Sequenom MassARRAY (USA). As a result, we identified an association with the manifestation age of T1D up to 30 years for rs1007856 of the gene ITGB5 (genotype TT, p=0,02), rs3765124 of the gene ADAMDEC1 (genotype AA, p=0,01). Differences received when comparing subgroups of T1D with different ages of manifestation: for rs1107946 of the gene COL1A1 (genotype AA, p=0,03) and rs514921 of the gene MMP1 (genotype AA, p=0,03). Genes whose SNPs have been associated with an age of manifestation of T1D are involved in the metabolism of extracellular matrix and collagen. Identified genetic variants can be considered as markers of the age of onset of T1D.
The features of the follicular thyroid cancer genetic determination
Authors: Штандель С.А. , Хазиев В.В. , Сазонов М.Е.
Published: November 2020

Комплексный анализ наследственной предрасположенности к фолликулярному раку щитовидной железы (ФРЩЖ) с использованием генеалогического, молекулярно-генетического методов и показателей отбора показал, что ФРЩЖ является генетически самостоятельной формой рака щитовидной железы, описывается параметрами полигенной пороговой модели, в его наследовании существенная роль принадлежит наследственным факторам (88,8%), имеются нелинейные межлокусные взаимодействия, отбор в пользу этой формы заболевания (Δs =0,041) и ассоциация мутаций Р12А и H449H во экзонах 2 и 6 гена PPARγ с фолликулярной структурой неоплазий.

The complex analysis of the follicular thyroid cancer (FTC) hereditary predisposition with using of genealogical, molecular methods and selection indexes is shown the FTC genetic independence; the distribution in the population and families may well be described by means of a variants polygene model with the importance role of genetic factors in determination of disease (88,8 %) and have allowed to assume the presence of interloci interactions in system of its genetic control; positive selection (Δs =0,041) of FTC and association of mutations Р12А and H449H in 2 and 6 exons of gene PPARγ with follicular structure of neoplasias.
Predicting the spread of head and neck cancer tumors to surrounding lymph nodes based on genetic testing
Authors: Угаров И.В. , Черных В.Б. , Иванов Н.В. , Масленников В.В. , Остапенко Д.К.
Published: November 2020

Рак головы и шеи (HNSC) - полигенное заболевание с тяжелыми инвалидизирующими последствиями и высокой смертностью, занимает 6 место среди онкологических заболеваний по распространенности в мире. Рост заболеваемости у людей до 40 лет, частое диагностирование в продвинутой стадии требуют разработки мер профилактики данного заболевания. Одним из способов решения такой задачи является выявление и использование в практике биомаркеров, выявляющих изменения на ранней доклинической стадии, и разработка подхода для оценки суммарного риска многофакторной патологии. Разработан подход и выявлены рисковые паттерны, характерные для пациентов с раком головы и шеи, математическая модель учитывает полиморфизмы в 17 генах и показывает чувствительность более 16% и специфичность более 93%. Валидация на тестовой выборке показала чувствительность 10% и специфичность 82%, что позволяет считать, что модель выявляет пациентов с высоким риском при наличии ключевых маркеров.

Head and neck cancer (HNSC) is a polygenic disease with severe disabling consequences and high mortality.it is the 6th most common cancer in the world. The increase in the incidence in people under 40 years of age, frequent diagnosis at an advanced stage requires the development of prevention measures for this disease. One of the ways to solve this problem is to identify and use in practice biomarkers that detect changes at an early preclinical stage and an approach for assessing the total risk of multifactorial pathology. An approach was developed and risk patterns typical for patients with head and neck cancer were identified. the mathematical model takes into account polymorphisms in 17 genes and shows a sensitivity of more than 16% and a specificity of more than 93%. Validation on a test sample showed 10% sensitivity and 82% specificity, which suggests that the prognosis identifies patients with high risk in the presence of key markers.
Survival of breast cancer patients treated with cyclophosphamide depending on the expression of the LTB4R leukotriene receptor gene in tumor tissue
Authors: Калинкин А.И. , Сигин В.О. , Стрельников В.В. , Танас А.С.
Published: November 2020

По результатам широкогеномного скрининга дифференциального метилирования в образцах рака молочной железы (РМЖ) нами было обнаружено аномальное деметилирование CpG-островка гена лейкотриенового рецептора LTB4R, которое может приводить к его эктопической экспрессии. В настоящей работе мы использовали данные, полученные при анализе 1083 образцов РМЖ в рамках проекта TCGA-BRCA, для определения влияния экспрессии LTB4R на эффективность лечения циклофосфамидом. Анализ кривых выживаемости пациенток с трижды-негативным (ТН) РМЖ с высокой экспрессией LTB4R в опухолях показал увеличение общей выживаемости при лечении циклофосфамидом (p<0,05). Для LumB подтипа РМЖ эффект циклофосфамида не зависел от экспрессии LTB4R. Полученные результаты расширяют возможности персонализации терапии РМЖ.

Based on the results of genome-wide screening of differential methylation in breast cancer samples (BC), we have identified abnormal demethylation of the LTB4R leukotriene receptor gene CpG island, which can lead to its ectopic expression. In this paper, we used the data obtained for 1083 BC samples under the TCGA-BRCA project to determine impact of LTB4R expression on the effectiveness of treatment with cyclophosphamide. Analysis of survival curves for patients with triple-negative (TN) breast cancer and high expression of LTB4R showed an increase in overall survival of patients treated with cyclophosphamide (p <0.05). For LumB BC subtype, the effect of cyclophosphamide was not dependent on LTB4R expression. The results obtained expand the possibilities of personalizing BC therapy.
Analysis of the miRNA-29 family expression in patients with clear cell renal cancer
Authors: Климентова Е.А. , Гилязова И.Р. , Измайлов А.А. , Султанов И.Р. , Искакова Г.М. , Виноградов Я.Г. , Павлов В.Н. , Хуснутдинова Э.К.
Published: November 2020

Почечно-клеточная карцинома (ПКК) является распространенной почечной неоплазией различных морфологических типов, среди которых светлоклеточная ПКК встречается наиболее часто. Считается, что семейство микроРНК-29, включающее микроРНК-29a, микроРНК-29b и микроРНК-29c, связано с агрессивностью и прогнозом течения злокачественных новообразований и может быть перспективным биомаркером для прогнозирования инициации, прогрессирования и патогенеза рака. Уровни экспрессии микроРНК-29a, -29b и -29c были определены в 30 парах образцов нормальной и опухолевой ткани почки пациентов с скПКК с использованием количественной ПЦР в реальном времени. Было обнаружено статистически значимое снижение экспрессии микроРНК-29a (Fold change=0,213; р-value=0,0016) в опухолевой ткани по сравнению с нормальной почечной паренхимой.

Renal cell carcinoma (RCC) is a common renal neoplasia of various morphological types, among which clear cell RCC is most common. It is believed that the miRNA-29 family, including miRNA-29a, miRNA-29b and miRNA-29c, is associated with aggressiveness and prognosis of malignant neoplasms and can be a promising biomarker for predicting the initiation, progression and pathogenesis of cancer. Expression levels of miRNA-29a, -29b, and -29c were determined in 30 pairs of normal and tumor tissue samples from the kidneys of patients with RCC using real-time quantitative PCR. A statistically significant decrease in miRNA-29a expression was found (Fold change = 0.213; p-value = 0.0016) in tumor tissue compared with normal renal parenchyma.
Significance of mutations in FGFR3, PIK3CA, TERT and TP53 genes in assessing the prognosis of non-muscle invasive bladder cancer
Authors: Михайленко Д.С. , Заборский И.Н. , Сергиенко С.А. , Сафиуллин К.Н. , Кузнецова Е.Б. , Алексеев Б.Я. , Залетаев Д.В. , Немцова М.В.
Published: November 2020

Имеющиеся сейчас прогностические классификаторы не всегда могут четко выделить группы низкого и высокого риска прогрессии рака мочевого пузыря (РМП). Нами проведен анализ мутаций FGFR3, PIK3CA, TERT и TP53 у 101 пациента с РМП. Показана обратная корреляция мутаций FGFR3, PIK3CA и/или TERT и прямая - ТР53 с увеличением злокачественности опухоли; до 25% пациентов в группах низкого и промежуточного риска немышечно-инвазивного РМП могут иметь мутации, ассоциированные с прогрессией заболевания.

Сurrently available prognostic classifications cannot clearly identify the cases of low and high risk of bladder cancer (BC) progression. We have analyzed the FGFR3, PIK3CA, TERT, and TP53 mutations in 101 BC patients. The correlation of TP53 mutations and absence of mutations in FGFR3, PIK3CA and/or TERT with tumor grade was observed; up to 25% of non-muscle invasive BC cases in low and intermediate risk groups harbor the mutations associated with the disease progression.
The significance of miR-146a for the regulation of NF-kB in metastatic gastric cancer
Authors: Кипкеева Ф.М. , Музаффарова Т.А. , Никулин М.П. , Апанович П.В. , Карпухин А.В.
Published: November 2020

Были изучены уровни экспрессии miR-146а и гена-мишени этой микроРНК - NF-kB в образцах рака желудка (РЖ) на разных этапах развития метастазов. Экспрессия miR-146а в образцах РЖ понижалась по мере вовлечения регионарных лимфоузлов в метастатический процесс. Была обнаружена отрицательная корреляция уровня экспрессии miR-146а со степенью поражения регионарных лимфоузлов (коэффициент корреляции по Спирмену (R) составил R = - 0,61; p=0,005). Напротив, экспрессия NF-kB повышалась при поражении лимфоузлов метастазами. Обнаружена обратная корреляция между miR-146a и NF-kB (R = -0,76; p=0,03). Впервые обнаруженная отрицательная корреляция экспрессии между miR-146a и NF-kB может указывать на активацию сигнального пути NF-kB в клетках РЖ при снижении экспрессии miR-146a. Видимо, этот сигнальный путь имеет значение при развитии метастазов РЖ.

The expression levels of miR-146a and the target gene of this miRNA, NF-kB, in gastric cancer (GC) samples at different stages of metastasis development were studied. The expression of miR-146a in the samples of the GC decreased with the involvement of regional lymph nodes in the metastatic process. A negative correlation was found between the expression level of miR-146a and the number of regional lymph nodes damage (Spearman’s correlation coefficient (R) was R = - 0.61; p 0.005). On the contrary, NF-κB gene expression increased with lymph node metastases. An inverse correlation was found between miR-146a and NF-κB (R = -0.76; p 0.03). The first detected negative correlation of expression between miR-146a and NF-κB may indicate activation of the NF-κB signaling pathway in GC cells with a decrease in miR-146a expression. Apparently, this signaling pathway is important in the development of metastases of gastric cancer.