Глюкозамін – перспективний коректор менопаузальних проявів

Genitourinary disorders occupy a significant place in the in the symptomatology of the climacteric syndrome and estrogen deficiency in women. In this regard, the urgent task of modern medicine and pharmacy is the search and creationof new medicines for correction and treatment of these menopausal symptoms.Aim. To study experimentally the efficacy of the genitourinary syndrome treatment with a new vaginal cream-gel containing 5 % glucosamine hydrochloride, in female rats with hypestrogenism.Materials and methods. The hypestrogenism status, which was close to the state of women at menopause, was modelled in rats using bilateral oophorectomy.Results. During the study it was found that after the 28-day intravaginal introduction of the cream-gel to female rats the pH value of the vaginal secretion was restored to 5.8 (p<0.05) compared to the group of animals of the control pathology up to the physiological range. The vaginal microbiocaenosis was also improved. A moderate decrease of the number ofopportunistic pathogens, increase of lactobacillus colonization by 1.3 times (p<0.05) compared to the group of animals of the control pathology and no effect on clostridia were observed. The study of the vaginal histostructure showed that the cream-gel had no “typical” estrogenic effects on the state of the vaginal mucosa compared to the reference drug – suppositories with estriol, but at the same time it reduced the manifestations of the endothelial dysfunction in the vaginal vessels.Conclusions. The test sample examined can be considered as promising for further studies in order to use it for pharmacological correction of the genitourinary menopausal syndrome in women.Значительное место в симптоматике климактерического синдрома и дефицита эстрогенов у женщин занимают генитоуринарные расстройства. В связи с этим актуальной задачей современной медицины и фармации является поиск и создание новых лекарственных препаратов для коррекции и лечения данных менопаузальных проявлений.Целью данной работы является экспериментальное изучение эффективности лечения генитоуринарного синдрома у самок крыс с гипоэстрогенией новым вагинальным крем-гелем, содержащим 5 % глюкозамина гидрохлорида.Материалы и методы. Моделирование у крыс гипоэстрогенового состояния, приближающегося к таковому у женщин в период менопаузы, осуществляли с помощью билатеральной овариоэктомии.Результаты. В ходе исследования было установлено, что после 28-дневного интравагинального введения крем-геля крысам восстанавливался показатель кислотности вагинального секрета до 5,8 (р<0,05) в сравнении сгруппой животных контрольной патологии, что соответствовало физиологическому диапазону. Отмечено также улучшение вагинального микробиоценоза, а именно умеренное уменьшение количества условно-патогенных микроорганизмов, увеличение колонизации лактобактерий в 1,3 раза (р<0,05) по отношению к животным, которым не вводили исследуемый тест-образец. Изучение гистоструктуры влагалища показало, что по сравнению с вагинальными суппозиториями с эстриолом крем-гель не оказывал «типичного» эстрогеноподобного влияния на состояние слизистой оболочки вагины, но при этом уменьшал проявления эндотелиальнойдисфункции в сосудах влагалища.Выводы. Исследуемый тест-образец можно считать перспективным для дальнейшего изучения с целью использования для фармакологической коррекции менопаузального генитоуринарного синдрома у женщин.Значне місце в симптоматиці клімактеричного синдрому і дефіциту естрогенів у жінок посідають генітоуринарні розлади. У зв’язку з цим актуальним завданням сучасної медицини і фармації є пошук і створення нових лікарських препаратів для корекції і лікування даних менопаузальних проявів.Метою роботи є експериментальне вивчення ефективності лікування генітоуринарного синдрому у самиць щурів з гіпоестрогенією новим вагінальним крем-гелем з глюкозаміну гідрохлоридом.Матеріали та методи. Моделювання у щурів гіпоестрогенового стану, близького до такого у жінок у період менопаузи, відтворювали шляхом білатеральної оваріоектомії самиць.Результати. Встановлено, що після 28-денного інтравагінального введення крем-гелю відновлювався показник кислотності вагінального секрету до 5,8 (р<0,05) порівняно з тваринами контрольної патології, що відповідало фізіологічному рівню. Також відмічене покращення вагінального мікробіоценозу, а саме помірне зменшення кількості умовно-патогенних мікроорганізмів, збільшення колонізації лактобактерій в 1,3 рази (р<0,05) повідношенню до тварин, яким не вводили досліджуваний тест-зразок. Вивчення гістоструктури піхви показало, що в порівнянні з вагінальними супозиторіями з естріолом крем-гель не чинив «типового» естрогеноподібно-го впливу на стан слизової оболонки піхви, але зменшував прояви ендотеліальної дисфункції у судинах піхви.Висновки. Отримані дані відкривають перспективи розробки нових вагінальних лікарських форм з глюкозаміну гідрохлоридом для фармакологічної корекції менопаузального генітоуринарного синдрому

Periodically modulated geometric and electronic structure of graphene on Ru(0001)

We report here on a method to fabricate and characterize highly perfect, periodically rippled graphene monolayers and islands, epitaxially grown on single crystal metallic substrates under controlled UHV conditions. The periodicity of the ripples is dictated by the difference in lattice parameters of graphene and substrate, and, thus, it is adjustable. We characterize its perfection at the atomic scale by means of STM and determine its electronic structure in the real space by local tunnelling spectroscopy. There are periodic variations in the geometric and electronic structure of the graphene monolayer. We observe inhomogeneities in the charge distribution, i.e a larger occupied Density Of States at the higher parts of the ripples. Periodically rippled graphene might represent the physical realization of an ordered array of coupled graphene quantum dots. The data show, however, that for rippled graphene on Ru(0001) both the low and the high parts of the ripples are metallic. The fabrication of periodically rippled graphene layers with controllable characteristic length and different bonding interactions with the substrate will allow a systematic experimental test of this fundamental problem.Comment: 12 pages. Contribution to the topical issue on graphene of Semiconductor Science and Technolog

Genetic aspects of potato resistance to phytophthorosis

Phytophthora infestans Mont. de Bary is the main oomycete pathogen of cultivated crops in the family Solanaceae, especially potato (Solanum tuberosum). Because potato is the fourth most cultivated crop worldwide, its annual losses from late blight are tremendous. Studies of the basic mechanisms of interaction between potato and the late blight pathogen not only expand the fundamental knowledge in this area, but also open up new possibilities for regulating these interactions in order to increase resistance to the pathogen. The interaction of potato and the late blight pathogen can be considered from a genetic point of view, and it is interesting to consider both the response of the potato to the colonization process by P. infestans and the change in gene activity in late blight during plant infection. We can also investigate this process by changing the profile of secondary metabolites of the host and the pathogen. In addition to fundamental work in this area, applied work in the form of the development of new preparations for protecting potatoes is of no less importance. This review briefly describes the main stages of studies of potato resistance to late blight, starting almost from the first works. Much attention is paid to key works on changing the profile of secondary metabolites phytoalexins. A separate section is devoted to the description of both qualitative and quantitative characteristics of potato resistance to the late blight pathogen: their contribution to overall resistance, gene mapping, and regulation capabilities. Both types of traits are important for potato breeding: quantitative resistance due to R-genes is quickly overcome by the pathogen, while quantitative trait loci make it possible to create varieties with almost absolute resistance due to the pyramid of effective genes. The latest approaches in molecular biology make it possible to study translatomic profiles, which makes it possible to look at the interaction of potatoes and the late blight pathogen at a different angle. It has been shown that the process of potato colonization affects not only the activity of various genes and the profile of secondary metabolites: proteins­markers of the response to infection from potatoes have also been identified: they are pathogen-bound proteins and plastid carbonic anhydrase. On the part of P. infestans, fungal cellulose synthase proteins and haustorium-specific membrane protein were markers of infection. Thus, the review contains information on the most relevant complex studies of the genetic mechanisms of potato resistance to late blight

Ribosomal profiling as a tool for studying translation in plants: main results, problems and future prospects

The expression of eukaryotic genes can be regulated at several stages, including the translation of mRNA. It is known that the structure of mRNA can affect both the efficiency of interaction with the translation apparatus in general and the choice of translation initiation sites. To study the translated fraction of the transcriptome, experimental methods of analysis were developed, the most informative of which is ribosomal profiling (RP, Ribo-seq). Originally developed for use in yeast systems, this method has been adapted for research in translation mechanisms in many plant species. This technology includes the isolation of the polysomal fraction and high-performance sequencing of a pool of mRNA fragments associated with ribosomes. Comparing the results of transcript coverage with reads obtained using the ribosome profiling with the transcriptional efficiency of genes allows the translation efficiency to be evaluated for each transcript. The exact positions of ribosomes determined on mRNA sequences allow determining the translation of open reading frames and switching between the translation of several reading frames – a phenomenon in which two or more overlapping frames are read from one mRNA and different proteins are synthesized. The advantage of this method is that it provides quantitative estimates of ribosome coverage of mRNA and can detect relatively rare translation events. Using this technology, it was possible to identify and classify plant genes by the type of regulation of their expression at the transcription, translation, or both levels. Features of the mRNA structure that affect translation levels have been revealed: the formation of G2 quadruplexes and the presence of specific motifs in the 5’-UTR region, GC content, the presence of alternative translation starts, and the influence of uORFs on the translation of downstream mORFs. In this review, we briefly reviewed the RP methodology and the prospects for its application to study the structural and functional organization and regulation of plant gene expression

Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats

Human and animal aging is associated with gradual decline of cognitive functions (especially learning ability and memory) and increased risk of development of neurodegenerative diseases 596 Abbreviations: bp, base pairs; mtDNA, mitochondrial DNA; ∆mtDNA, deletion in mitochondrial DNA; ∆mtDNA 4834 , 4834-bp mitochondrial DNA deletion; ROS, reactive oxygen species; SkQ1, antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium. * To whom correspondence should be addressed. Abstract-Reduction of efficiency of oxidative phosphorylation associated with aging and the development of neurodegenerative diseases including Alzheimer's disease is thought to be linked to the accumulation of deletions in mitochondrial DNA (∆mtDNA), which are seen as a marker of oxidative damage. Recently, we have shown that mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium) can slow the development of signs of Alzheimer's disease in senescence-accelerated OXYS rats. The purpose of this study was to explore the relationship between the development of neurodegenerative changes in the brain of OXYS rats and changes in the amount of mtDNA and the 4834-bp mitochondrial DNA deletion (∆mtDNA 4834 ) as well as the effect of SkQ1. We studied the relative amount of mtDNA and ∆mtDNA 4834 in the hippocampus of OXYS and Wistar (control) rats at ages of 1, 2, 6, 10, and 20 days and 3, 6, and 24 months. During the period crucial for manifestation of the signs of accelerated aging of OXYS rats (from 1.5 to 3 months of age), we evaluated the effects of administration of SkQ1 (250 nmol/kg) and vitamin E (670 mmol/kg, reference treatment) on the amount of mtDNA and ∆mtDNA 4834 and on the formation of the behavioral feature of accelerated senescence in OXYS rats -passive type of behavior in the open field test. In OXYS rats, the level of ∆mtDNA 4834 in the hippocampus is increased compared to the Wistar rats, especially at the stage of completion of brain development in the postnatal period. This level remains elevated not only at the stages preceding the manifestation of the signs of accelerated brain aging and the development of pathological changes linked to Alzheimer's disease, but also during their progression. However, at age of 24 months, there were no detectable differences between the two strains. SkQ1 treatment reduced the level of ∆mtDNA 4834 in the hippocampus of Wistar and OXYS rats and slowed the formation of passive behavior in OXYS rats. These results support the possible use of SkQ1 for prophylaxis of brain aging. Influence of Antioxidant SkQ1 o

Methodological approaches for producing doubled haploids in sugar beet and red beet (Beta vulgaris L.)

The in vitro production of doubled haploids is a biotechnological path of an accelerated development of parental lines in F1-hybrid breeding programs. Unlike the traditional inbreeding method requiring 5 to 6 generations to reach a suf­ficient homozygosity of lines, the number of generations to produce pure lines of beet by haploid technologies is reduced to 2. The production of doubled haploids by gynogenesis is the most common biotechnological approach in sugar and red beets. Protocols for the production of doubled haploids for B. vulgaris species are few and have been developed mainly for sugar beets. There are no protocols for the production of doubled haploids for red beet (B. vulgaris convar. esculenta Salisb.), and the protocols developed for sugar beet (B. vulgaris convar. saccharifera Alef.) are ineffective for red beet, even though these two crops belong to the same species. The greatest success has been achieved in the production of doubled haploids by gynogenesis through isolated ovule culture, especially in sugar beet. Studies on the production of doubled haploids by androgenesis were actively carried out in the 1970s and 1980s and did not lead to the production of regenerated plants. However, at present, there is renewed interest among researchers in this approach, and scientists in different countries are conducting studies of Beta vulgaris androgenesis through isolated microspore culture. This article provides an overview of studies devoted to the production of doubled haploids, addressing the main problems of doubled haploid technologies, and methods to increase the frequency of embryogenesis and doubled haploid plant formation in B. vulgaris crops

Orientation-controlled, low-temperature plasma growth and applications of h-BN nanosheets

Dimensionality and orientation of hexagonal boron nitride (h-BN) nanosheets are promising to create and control their unique properties for diverse applications. However, low-temperature deposition of vertically oriented h-BN nanosheets is a significant challenge. Here we report on the low-temperature plasma synthesis of maze-like h-BN nanowalls (BNNWs) from a mixture of triethylamine borane (TEAB) and ammonia at temperatures as low as 400 °C. The maze-like BNNWs contained vertically aligned stacks of h-BN nanosheets. Wavy h-BN nanowalls with randomly oriented nanocrystalline structure are also fabricated. Simple and effective control of morphological type of BNNWs by the deposition temperature is demonstrated. Despite the lower synthesis temperature, thermal stability and oxidation resistivity of the maze-like BNNWs are higher than for the wavy nanowalls. The structure and oxidation of the nanowalls was found to be the critical factor for their thermal stability and controlled luminescence properties. Cytotoxic study demonstrated significant antibacterial effect of both maze-like and wavy h-BN nanowalls against E. coli. The reported results reveal a significant potential of h-BN nanowalls for a broad range of applications from electronics to biomedicine. [Figure not available: see fulltext.]. © 2018, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature

Проблемы проведения биоаналитической части исследований биоэквивалентности лекарственных препаратов в России

In the review of the main problems holding bioanalytical part of bioequivalence studies of medicines in Russia. The analysis of the major causes of failure when performing studies of bioequivalence and pharmacokinetics.В обзоре рассмотрены основные проблемы проведения биоаналитической части исследований биоэквивалентности лекарственных препаратов в России. Проведен анализ основных причин неудач при выполнении исследований по биоэквивалентности и фармакокинетике

Первый опыт суперселективной эмболизации артерий, кровоснабжающих опухоль, с последующей лапароскопической резекцией почки

Background. Patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors are at high risk of functional failure or insufficiency of the kidney after surgery. Joint discussions with specialists in X-ray endovascular surgeries resulted in the development of a treatment algorithm for patients with localized kidney cancer who require organ-sparing surgery without ischemic kidney resection.Objective: to evaluation of the immediate results of two-stage surgical treatment of localized kidney cancer in patients with signs of tumor lesions in a single kidney or in the only one functioning kidney, with bilateral renal tumors, including superselective embolization of the artery supplying the tumor at the first stage, and laparoscopic kidney resection without renal ischemia parenchyma at the second stage.Materials and methods. This study included 5 patients with localized kidney cancer, who underwent two-stage treatment at Moscow Regional Oncology Dispensary between 24.03.2021 and 19.04.2021. The first stage included superselective embolization of the artery supplying the tumor; the second stage implied laparoscopic kidney resection 6-7 days following the first stage.Results. The median age of the patients was 62 years (range: 42-73 years). Four patients (80%) had unilateral kidney lesions, while 1 patient (20 %) had bilateral (synchronous) kidney cancer. The mean RENAL score was 8 (range: 6-10); patients were distributed as follows: score 4-6 in 40 %, score 7-9 in 40 %, and score >10 in 20 % of patients. At the first stage, patients underwent endovascular embolization of the branches of the renal artery. Patients had superselective embolization of either middle (n = 3; 60 %), upper (n = 1; 20 %), or lower (n = 1; 20 %) segmental arteries supplying the tumor. In one of them (20 %), we identified 3 large arterial branches; in another one (20 %), we identified 2 large arterial branches.At the second stage, we performed laparoscopic kidney resection. None of the patients required renal artery clamping, because there was an excellent visualization of the demarcation zone and no significant blood loss. The resection area was sutured in 1 case (20 %). In 2 individuals (40 %), a hemostatic sponge was installed in the removed tumor bed. In the remaining 2 cases (40 %), hemostasis was ensured by coagulation. The median blood loss was 100 mL (range: 50-200 mL). The postoperative period was uneventful in all patients. None of the patients developed symptoms of acute renal failure.Conclusion. Thus, superselective embolization of arteries supplying a kidney tumor has undeniable advantages in organ-sparing surgeries for patients with localized kidney cancer and some additional kidney problems, when organ preservation is crucial for patient's life.Введение. Больные с признаками опухолевого поражения единственной или единственной функционирующей почки, с двухсторонними опухолями почек представляют собой категорию, ассоциированную с высоким риском потери функции почки или функциональной недостаточности почки после оперативного лечения. Совместные обсуждения с рентгенэндоваскулярными хирургами привели к формированию алгоритма действий при лечении больных локализованным раком почки, требующих органосохраняющей тактики в условиях без ишемической резекции почки.Цель исследования - оценка непосредственных результатов двухэтапного хирургического лечения локализованного рака почки у больных с признаками опухолевого поражения единственной, единственной функционирующей почки или с двухсторонними опухолями почек, включающего на 1-м этапе суперселективную эмболизацию артерии, питающей опухоль, на 2-м этапе - лапароскопическую резекцию без ишемии почечной паренхимы.Материалы и методы. В исследование были включены 5 пациентов с локализованным раком почки, которым с 24.03.2021 по 19.04.2021 в Московском областном онкологическом диспансере г. Балашихи выполнено двухэтапное лечение. На 1-м этапе проведена суперселективная эмболизация артерии, питающей опухоль, на 2-м этапе, через 6-7 сут, - лапароскопическая резекция почки.Результаты. Медиана возраста больных составила 62 (42-73) года. У 4 (80 %) пациентов было одностороннее поражение почки, у 1 (20 %) - двухсторонний (синхронный) рак почек. Средняя сумма баллов по шкале RENAL составила 8 (6-10): 4-6 баллов - у 40 %, 7-9 баллов - у 40 % и >10 баллов - у 20 % больных. На 1-м этапе лечения проводили эндоваскулярную эмболизацию ветвей почечной артерии. В 3 (60 %) случаях выполнена суперселективная эмболизация средних сегментарных артерий, по 1 (20 %) случаю - верхней и нижней сегментарных артерий, питающих опухоль, из них в 1 (20 %) случае выявлены 3 крупные артериальные ветви и в 1 (20 %) случае - 2 артериальные ветви.На 2-м этапе выполняли лапароскопическую резекцию почки. В 100 % случаев ввиду отсутствия значительной кровопотери и отличной визуализации демаркационной зоны не потребовалось пережатия почечных артерий. Прошивание области резекции проводили в 1 (20 %) случае. В 2 (40 %) случаях в ложе удаленной опухоли установлена гемостатическая губка. В остальных 2 (40 %) случаях гемостаз осуществляли коагуляционным способом. Медиана объема кровопотери составила 100 (50-200) мл. Послеоперационный период у всех больных протекал без особенностей. Явлений острой почечной недостаточности не наблюдалось ни у одного пациента.Заключение. Выполнение суперселективной эмболизации артерий, питающих опухоль почки, имеет неоспоримые преимущества при планировании органосохраняющих операций при локализованном раке почки у больных с отягощенным «почечным» анамнезом, при котором сохранение органа имеет принципиальное значение

Beta-HPV 5 and 8 E6 Promote p300 Degradation by Blocking AKT/p300 Association

The E6 oncoprotein from high-risk genus alpha human papillomaviruses (α-HPVs), such as HPV 16, has been well characterized with respect to the host-cell proteins it interacts with and corresponding signaling pathways that are disrupted due to these interactions. Less is known regarding the interacting partners of E6 from the genus beta papillomaviruses (β-HPVs); however, it is generally thought that β-HPV E6 proteins do not interact with many of the proteins known to bind to α-HPV E6. Here we identify p300 as a protein that interacts directly with E6 from both α- and β-HPV types. Importantly, this association appears much stronger with β-HPV types 5 and 8-E6 than with α-HPV type 16-E6 or β-HPV type 38-E6. We demonstrate that the enhanced association between 5/8-E6 and p300 leads to p300 degradation in a proteasomal-dependent but E6AP-independent manner. Rather, 5/8-E6 inhibit the association of AKT with p300, an event necessary to ensure p300 stability within the cell. Finally, we demonstrate that the decreased p300 protein levels concomitantly affect downstream signaling events, such as the expression of differentiation markers K1, K10 and Involucrin. Together, these results demonstrate a unique way in which β-HPV E6 proteins are able to affect host-cell signaling in a manner distinct from that of the α-HPVs