Inflammaging as the basis of age-associated diseases

Aging is one of the most complex biological phenomena that affects all human physiological systems, including the immune system. Immunosenescence is understood as structural and functional changes in both adaptive and innate immunity systems. The so-called inflammaging is among manifestations of immune aging. It is an age-related increase in inflammatory mediators and development of an inflammatory phenotype. An important role in development of inflammaging is assigned to chronic stimulation of immune system by exogenous and endogenous danger signals (pathogen-associated molecular pattern, PAMP and damage-associated molecular pattern, DAMP), which include viruses, microbiota of the gastrointestinal tract, free radicals, etc. PAMP and DAMP are recognized by the innate immunity system cells through the pattern recognition receptors (PRR), e.g., Toll-like receptors (TLR), RIG-I-like receptors (RLR), NODlike receptors (NLR), lectin receptors. Stimulation of PRR leads to activation of intracellular signaling and increased expression of pro-inflammatory factors. PAMPs are the most powerful activators of PRR and inflammation triggers; DAMPs can activate the same receptors and signaling pathways, causing the development of a sterile inflammatory response. The NF-kB signaling pathway is considered as a key signaling pathway for inflammaging. NLR stimulation also leads to formation of inflammasome. Its function is to transform the pro-inflammatory cytokines to a biologically active form, which is an important for the formation of a pro-inflammatory phenotype and development of inflammaging. This process is considered an important risk factor for morbidity and mortality among older people. Chronic inflammation underlies pathogenesis of many age-related diseases, such as osteoporosis, atherosclerosis, Alzheimer’s disease, Parkinson’s disease, type 2 diabetes. Various chronic diseases associated with age are directly related to PAMP and DAMP-induced TLR or NLRP3-mediated inflammatory response. Hence, these ligands and their receptors can be suggested as biomarkers and interventional targets for age-related disorders. Despite numerous studies in age-associated pathology, there are only few works on the contribution of innate immunity in healthy aging. It remains unclear whether the inflammatory phenotype is a manifestation of healthy aging, or it is associated with development of age-related pathology. Further study of the mechanisms of inflammatory aging will reveal biomarkers of healthy aging and potential targets for the treatment of age-associated diseases

Genetic resources of vegetable crops: from breeding non-traditional crops to functional food

In this review, the authors considered the promising species of vegetable crops for introduction and breeding in the Russian Federation. An attempt was made to assess the possibilities of their breeding improvement from the standpoint of the presence of traits that limit large-scale production. Species that could potentially serve as sources of a high content of functional food ingredients (FFI) have been identified and characterized. For the successful introgression of these species in the Russian Federation, we proposed the methodological approaches including the assessment of the potential cold resistance of thermophilic crops in the mature male gametophyte in vitro (e. g., asparagus bean). The increase in the biodiversity of vegetable plants and improving of their nutritional value should be recognized as one of the main tasks, along with the growth of crop productivity. It is proposed to use the ratio of the total number of the registered cultivars of a particular crop to the number of years since the first cultivar of that crop has been included in the State Register of Breeding Achievements Admitted for Use as a measure of demand. It is advisable to formalize the trait“high content of FFI” in crops, taking as a basis, for example, a 2–4-fold excess of the content of any FFI or their complex in a cultivar over the crop’s standard (reference) value. Such varieties should be included in the State Register of Breeding Achievements Approved for Use as a separate list. The purpose of their separation in the State Register is to ensure the potential interest of investors and business structures in the sale of functional food on the market. The paper discusses in detail the most promising species of introduced vegetable crops from five families (Brassicaceae, Amaranthaceae, Solanaceae, Leguminosae, Cucurbitaceae). The following species are proposed as potential sources of high FPI content: Brassica oleracea ssp. oleracea, B. oleraceae var. alboglabra, B. rapa ssp. chinensis, B. rapa ssp. narinosa, B. rapa ssp. nipposinica, B. rapa ssp. rapa, B. uncea, Cochlearia officinalis, Lepidium sativum, Amaranthus caudatus, A. cruentus, A. hypochondriacus, A. dubius, A. tricolor, lividus, species in the genus Physalis L., Momordica charantia, Benincasa hispida, Cucumis metuliferus, Vigna unguiculata

Nail psoriasis: dynamics of the clinical course during anti-IL-17 therapy

Psoriasis is a chronic immune-mediated inflammatory disease in which the pathological process quite often involves the nail apparatus. Psoriatic onychodystrophy is considered a serious psychological and social problem, as nail lesions are not only a cosmetic defect, they can also complicate daily activities, including employment, ability to work and generally impair the quality of life of patients. In addition, numerous studies and clinical practice show that nail lesions in psoriasis are also associated with a more severe course of the skin process, and are rather torpid to therapy. Moreover, psoriatic onychodystrophy is considered as a form of enthesitis, which is in fact an important predictor of the development of psoriatic arthritis. Various topical, systemic and physiotherapeutic options have been recommended in the therapy of psoriasis with nail plate damage, but the effectiveness of these therapeutic methods is in most cases insufficient and the search for highly effective treatment is of great clinical importance at present. Taking into consideration the critical importance of interleukin (IL)-17 in the pathogenesis of psoriasis, its inhibitors allow to achieve a stable remission of cutaneous and joint processes, thus, it is promising in the therapy of psoriatic onychodystrophy. The article presents the literature data on epidemiology, clinical picture of nail changes in psoriasis, the review of effective pathogenetic methods of psoriatic onychodystrophy therapy and personal clinical observations of patients with severe psoriasis with nail plate damage treated with Russian interleukin 17A inhibitor – Netakimab. These observations allow to draw a conclusion about high efficacy of netakimab in the therapy of patients with psoriasis including the presence of such hardtop-treat localizations as nail lesions

Научная специальность «Библиотековедение, библиографоведение и книговедение» и профильные диссертационные исследования (1999–2020)

In the modern world, global changes are taking place in all spheres of society, including economy, science, education and culture. In this regard, a detailed analysis and comprehension of ongoing processes become relevant to develop a specific strategy. In 2021, the Ministry of Science and Higher Education adopted the Order «On the approval of the nomenclature of scientific specialties for which scientific degrees are awarded <….>”; the nomenclature of scientific specialties was published, where specialty 05.25.03 «Library Science, Bibliography science and Bibliology» was not reflected (among pedagogical, historical, philological, technical sciences). This document came next to a draft nomenclature of scientific specialties (2020), which was widely discussed by the scientific community. The library community and representatives of university science carried out a number of activities aimed at changing the situation. The authors recreate the picture of forming and growing the profile scientific specialty, including its presentation in the nomenclature of scientific specialties for which scientific degrees are awarded since 1957; analyze statistic materials on post-graduate training of highly qualified scientific personnel and activity to defense dissertations in 1999–2020; generalize and assess the data, consider the problems and vectors of this specialty development to justify the inclusion of the specialty «Library Science, Bibliography Science and Bibliology» in the new nomenclature of scientific specialties to continue the training of highly qualified scientific personnel in graduate school, and to carry out specialized research. The article argues that the consequences of the ongoing reforms in science have led to transformations, slowing down the rotation of scientific personnel, extinguishing the activities of dissertation councils and scientific schools in library science, bibliography and bibliology in the regions and complicating the development of library and information science in general.В современном мире происходят глобальные изменения во всех сферах общества, в том числе в экономике, науке, образовании и культуре. В связи с этим становятся актуальными детальный анализ и осмысление происходящих процессов с целью выработки определенной стратегии. В 2021 г. Министерством науки и высшего образования был принят Приказ «Об утверждении номенклатуры научных специальностей, по которым присуждаются ученые степени <….>», опубликована номенклатура научных специальностей, в которую специальность 05.25.03 «Библиотековедение, библиографоведение и книговедение» (отрасли: педагогические, исторические, филологические, технические науки) не была включена. Авторы воссоздают картину формирования и становления профильной научной специальности, представления ее в номенклатуре научных специальностей, по которым осуществляется присуждение ученых степеней, начиная с 1957 г., подробно анализируют статистические материалы по подготовке научных кадров высшей квалификации в аспирантуре, проведению защит диссертаций в 1999– 2020 гг., осуществляют обобщение сведений, дают им оценку и рассматривают проблемы и векторы развития специальности с целью обоснования включения специальности «Библиотековедение, библиографоведение и книговедение» в новую номенклатуру научных специальностей, продолжения осуществления подготовки научных кадров высшей квалификации в аспирантуре и проведения профильных исследований. В статье аргументировано, что последствия проводимых реформ в науке привели к трансформациям, замедлившим ротацию научных кадров, угасанию деятельности диссертационных советов и научных школ по библиотековедению, библиографоведению и книговедению в регионах и осложнению развития библиотечно-информационной науки в целом

Опыт применения генозаместительной терапии препаратом Золгенсма® (онасемноген абепарвовек) в реальной клинической практике в России

Objective: to analyze the safety and evaluate the effectiveness of therapy with onasemnogene abeparvovec in patients with spinal muscular atrophy in real clinical practice based on the experience of using the drug in the neuromuscular center of Research Clinical Pediatric Institute of Pirogov Russian National Research Medical University.Materials and methods. Patients with spinal muscular atrophy received therapy with onasemnogene abeparvovec based on the prescription of the drug according to vital indications by a council of physicians of Federal institutions (the availability of the drug was carried out within the framework of the MAP Program (global program of managed access MAP to AVXS-101 for eligible patients in countries, where it is not approved by regulatory authorities (NCT03955679), through funding from the charitable foundations, as well as through funding from the state fund “Circle of Kindness”. The drug tolerance was assessed and the analysis of side effects after drug administration was based on the criteria for adverse events (General criteria Adverse Event Terminology (CTCAE) v. 5.0) Patient motor function was assessed prior to treatment initiation and every 3–6 months after therapy using the Philadelphia Pediatric Hospital’s CHOP INTEND scale, total motor development based on Hammersmith Hospital Neurological Assessment Scale in Young Children, Part 2 (HINE-2), and the acquisition of new motor skills.Results. 41 children aged 5 to 47 months (weighing no more than 21 kg) received therapy with onasemnogene abeparvovec in the period from April 2020 to December 2021. Adverse events (hyperthermia, decreased appetite, nausea, vomiting) were registered in all patients with different degree of severity. Elevated levels of transaminases greater than 2 times the upper limit of the normal range were observed in 32 patients (78 %), thrombocytopenia in 9 patients (22 %). 15 patients (36 %) required a dose adjustment of corticosteroids.17 patients underwent assessment of motor scales after 6 months, 10 children were assessed after a year. The average improvement on the HINE-2 scale was 3.3 / 4.4 points, respectively. The average improvement on the CHOP INTEND Scale was 7.1 / 9.4 points after 6 / 12 months of therapy.Conclusion. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in real clinical practice in the treatment of spinal muscular atrophy for children in different age groups with a body weight of no more than 21 kg.Цель исследования – проанализировать безопасность и оценить эффективность терапии препаратом Золгенсма® (онасемноген абепарвовек) у пациентов со спинальной мышечной атрофией в реальной клинической практике на основании опыта применения препарата в нервно-мышечном центре ОСП «Научно-исследовательский клинический институт педиатрии им. акад. Ю. Е. Вельтищева» ФГБОУ ВО РНИМУ им. Н. И. Пирогова.Материалы и методы. Пациенты со спинальной мышечной атрофией получали терапию препаратом онасемноген абепарвовек на основании назначения препарата по жизненным показаниям консилиумом врачей федеральных учреждений (доступность к препарату осуществлялась в рамках Программы MAP (глобальная программа управляемого доступа MAP к препарату AVXS-101 для пациентов, соответствующих критериям, в странах, где он не был одобрен регулирующими органами (NCT03955679)), за счет финансирования благотворительных фондов, а также за счет финансирования государственным фондом «Круг добра». Проведены оценка переносимости препарата и анализ побочных эффектов после введения препарата на основании критериев нежелательных явлений (Общие критерии терминологии для нежелательных явлений (CTCAE) v. 5.0). Оценивались моторная функция пациентов до начала терапии и каждые 3–6 мес после терапии с помощью шкалы детской больницы Филадельфии для диагностики двигательных функций у новорожденных (CHOP INTEND), общее двигательное развитие по шкале оценки неврологического статуса больницы Хаммерсмит у детей раннего возраста, часть 2 (HINE-2), а также приобретение новых двигательных навыков.Результаты. Терапию препаратом онасемноген абепарвовек получил 41 ребенок в возрасте от 5 до 47 мес (с массой тела не более 21 кг) в период с апреля 2020 г. по декабрь 2021 г. Нежелательные явления (гипертермия, снижение аппетита, тошнота, рвота) зарегистрированы у всех пациентов с разной степенью выраженности. Повышение уровня трансаминаз более чем в 2 раза от верхней границы нормы было отмечено у 32 (78 %) пациентов, тромбоцитопения – у 9 (22 %); 15 (36 %) пациентам потребовалась коррекция дозы кортикостероидов.Семнадцати пациентам проведена оценка по двигательным шкалам через 6 мес, 10 детям – спустя год. Среднее улучшение по шкале HINE-2 составило 3,3 / 4,4 балла соответственно. Среднее улучшение по шкале CHOP INTEND составило 7,1 / 9,4 балла через 6 / 12 мес терапии.Заключение. Продемонстрированы эффективность и безопасность применения препарата онасемноген абепарвовек в условиях реальной клинической практики при терапии спинальной мышечной атрофии для детей в разных возрастных группах с массой тела не более 21 кг

Endometrial expression of FOX proteins (FOXA1 and FOXA2) in women of reproductive age with different endometrial thickness: prospective cohort comparative study

Aim. To evaluate the expression of FOX proteins (FOXA1 and FOXA2) in the endometrium during the implantation window in women with a history of reproductive dysfunctions with different thickness of the endometrium. Materials and methods. The prospective cohort comparative study was conducted. The main group included patients with "thin" endometrium (7 mm according to ultrasound on preovulatory days; n=52), the comparison group consisted of women with normal endometrial thickness (7 mm according to ultrasound; n=62; women of both groups with reproductive dysfunctions of unknown reason), the control group included 16 healthy fertile women. Aspiration biopsy of the endometrium was performed on the 68 days after ovulation, as well as venipuncture to obtain a sample of peripheral blood to determine the levels of sex steroids (estradiol E2 and progesterone P). A combined histological and immunohistochemical study of endometrial biopsies was performed. Results. All women had ovulatory values of progesterone P16.1 nmol/l (68 days after ovulation) and normoestrogenemia (E2, pmol/l) in the blood. E2/P was similar in all groups (p0, 05). A pronounced expression of FOXA1 was noted in women with thin endometrium significantly more often (p0.05) with various hormone-receptor characteristics of the endometrium (42% n=22 out of 52) compared with healthy participants (0%; n=0). Reduced FOXA2 expression in the uterine mucosa was significantly more often detected on 68 days after ovulation in women with "thin" endometrium (56% n=29 of 52) than in women with normal endometrial thickness, both in women from the comparison group and in healthy women from the control group (p0.05). In a generalized analysis of the expression of FOX proteins in the endometrium on days 68 after ovulation, it was generally found that every second (50%; n=57 out of 114) women with a history of reproductive disorders (with a reduced and normal M-echo value) expression of proteomic markers differed from healthy women. In the case of "thin" endometrium, more than two thirds of patients (71%; n=37 out of 52) showed differences in endometrial expression of FOX proteins compared with women without a burdened reproductive history. Conclusion. In the majority of women (71%) with a thin endometrium and a history of reproductive dysfunctions, the expression of FOX proteins in the endometrium differed from the control group. Overall, endometrial expression of FOX proteins, which is likely to be different from healthy women, in patients with reproductive dysfunctions of unknown origin is a significant predictor of reproductive failure. At the same time, such an isolated indicator as M-echo value 7 mm according to ultrasound data is not an absolute prognostic marker of endometrial receptivity disorders

Изучение полиморфизма генов R2R3 Myb транскрипционных факторов культур семейства Solanaceae и гена Myb114 рода Brassica в связи с регуляцией биосинтеза антоцианов

Based on comparison of R2R3 Myb genes in Solanaceae (S. lycopersicum: Ant1, Ant2, S. melongena: Myb1, C. annuum: Myb113-like1 and Myb113-like2) and Brassicaceae crops, a search for orthologous sequences was The sequences encoding Myb114 TF in Brassica oleracea and Brassica rapa was found to be the closest in a nucleotide structure to the previously investigated genes in Solanaceae. Тhе polymorphism in the promoter region of the Capsicum annuum Myb113-like1 gene that regulates anthocyanin biosynthesis: an additional 148 bp repeat and 2(1) bp insertion in the forms with impaired anthocyanin synthesis in fruits was studied. A relationship between the presence of an insert in the promoter (Myb113-like1pr+148) and polymorphisms in the exon regions of Myb113-like1delTand Myb113-like2C/Аgenes associated with impaired anthocyanin synthesis was established. A number of polymorphisms of the Myb114 gene in vegetable crops of the cabbage family (Brassica oleracea, Brassica rapa), which closely correlate with high/low accumulation of anthocyanins in leaves, were identified. In B. oleracea, SNPs that lead to the replacement of two amino acids located in the region of DNAbinding domains were found, which leads to a change in the efficiency of binding of this transcription factor and the promoters of structural biosynthesis genes. A protein sequence encoded by the Myb114 gene in accessions of the leafy turnip (B. rapa) with a high accumulation of anthocyanins in the leaves differed from the accessions without anthocyanin accumulation in the leaves by five amino acids, while the regions of DNA-binding domains were the same in the forms with various anthocyanin accumulation.На основе сравнения генов R2R3 Myb транскрипционных факторов у овощных пасленовых (S. lycopersicum: Ant1, Ant2, S. melongena: Myb1, C. annuum: Myb113-like1 и Myb113-like2) и капустных культур выполнен поиск ортологичных последовательностей. Выявлены наиболее близкие по нуклеотидной структуре к ранее изученным генам у пасленовых последовательности, кодирующие Myb114 ТФ у Brassica oleracea и Brassica rapa. Изучен полиморфизм в промоторной области гена Myb113-like1 Capsicum annuum, регулирующего биосинтез антоцианов: дополнительный повтор размером 148 п. н. и вставка 2 (1) п. н. у форм с нарушенным синтезом антоцианов в плодах. Установлена связь между наличием вставки в промоторе (Myb113-like1pr+148) с полиморфизмами в экзонных областях генов Myb113-like1delT и Myb113-like2C/А, связанными с нарушением синтеза антоцианов. Выявлен ряд полиморфизмов гена Myb114 у овощных культур семейства капустных (Brassica oleracea, Brassica rapa), тесно коррелирующих с высоким/низким накоплением антоцианов в листьях. У B. oleracea выявлены SNP, которые ведут к замене двух аминокислот, расположенных в области ДНК-связывающих доменов, что приводит к изменению эффективности связывания данного транскрипционного фактора с промоторами структурных генов биосинтеза. Белковая последовательность, кодируемая геном Myb114, у образцов B. rapa разновидности репа листовая с высоким накоплением антоцианов в листьях отличалась от таковой у образцов с отсутствием антоцианов в листьях пятью аминокислотами, при этом области ДНК-связывающих доменов были одинаковыми у форм с различным накоплением антоциана

Основополагающее значение понятий «амбулаторность» и «неамбулаторность» в комплексной оценке состояния пациентов с мышечной дистрофией Дюшенна

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease due to a mutation in the gene encoding dystrophin synthesis. In patients, muscle damage and atrophy progresses, the ability to move independently decreases as well as respiratory and cardiac functions. At various stages of the disease, different methods of care and treatment of patients with DMD are used. The clinical effect of new methods of DMD target therapy may depend on the stage of development of the disease (ambulatory or non‑ambulatory). To date, there are no unified criteria for assessing the status of a patient in terms ambulatory. In clinical trials and real clinical practice, different approaches are used to assess the patient’s status. However, the conclusion about the functional capabilities is critical for patients with DMD as approaches in management of patients in ambulatory and non‑ambulatory stages differ significantly. This necessitates expert consensus to achieve consistency and avoid any of discrepancies on that issue.The paper reviews the available published data on the concepts of “ambulatory” and “non‑ambulatory” used in clinical trials, real clinical practice, international standards and recommendations. As a conclusion of this analysis, it is proposed in real clinical practice to interpret “ambulation” in DMD patients as ability to walk without the use of assistive devices and without specifying the distance and time, and “non‑ambulation” as condition in which the patient is forced to constantly use a wheelchair both indoors and outdoors.Мышечная дистрофия Дюшенна (МДД) – фатальное нервно‑мышечное заболевание, обусловленное мутацией гена, кодирующего белок дистрофин. В результате развивающегося и прогрессирующего повреждения и атрофии мышц пациенты теряют способность к самостоятельному передвижению, у них развиваются респираторные и кардиологические нарушения. На разных стадиях МДД используются разные методы ведения. Клинический эффект новых методов таргетной терапии МДД может зависеть от стадии болезни на момент назначения лечения: амбулаторной, когда пациент ходит самостоятельно, или неамбулаторной, когда способность к самостоятельной ходьбе утрачена. Сегодня нет единых критериев статуса пациента с точки зрения амбулаторности, а в клинических исследованиях и реальной практике используются разные подходы к ее оценке. Тем не менее определение понятий «амбулаторность» и «неамбулаторность» критично для пациентов с МДД, так как подходы к ведению пациентов в амбулаторной и неамбулаторной стадии болезни различны. В статье представлены обзор, сравнение и анализ определений «амбулаторность» и «неамбулаторность», использованных в клинических исследованиях, реальной медицинской практике, международных стандартах и рекомендациях.По итогам анализа предлагается в реальной клинической практике трактовать амбулаторность больных МДД как способность ходить без использования вспомогательных средств и без указания дистанции и времени, а потерей амбулаторности считать состояние, при котором пациент вынужден постоянно использовать инвалидное кресло для передвижения как вне дома, так и в домашних условиях