Effect of the host-specific toxin SnTOX3 from Stagonospora nodorum on ethylene signaling pathway regulation and redox-state in common wheat

The fungus Stagonospora nodorum Berk. is the causative agent of Septoria nodorum blotch (SNB) of wheat. The most important factors of Stagonospora nodorum virulence include numerous fungal necrotrophic effectors (NEs) encoded by SnTox genes. They interact with the matching products of host susceptibility genes (Snn). SnTox-Snn interactions are mirror images of classical gene-for-gene interactions and lead to the development of disease. We have studied the SnTox3-Snn3 interaction, resulting in the development of infection on leaves and formation of extensive lesions. The mechanism of SnTox3 action is likely to be linked to the regulation of redox metabolism and the influence on ethylene synthesis in the wheat plants, although the molecular mechanisms are not fully unveiled. To characterize the SnTox3-Snn3 interaction, we used S. nodorum isolates differing in the expression of the NEs genes SnTox3 (SnB (Tox3+), Sn4VD (Tox3–)) and two soft spring wheat (Triticum aestivum L.) cultivars, contrasting in resistance to the SNB agent and differing in the allelic composition of the susceptibility locus Snn3-B1: Kazakhstanskaya 10 (susceptible) and Omskaya 35 (resistant). We carried out a comparative assessment of the transcriptional activity patterns of genes responsible for ethylene biosynthesis (TaACS1, TaACО) and signaling pathway (TaEIL1, TaERF1) by real-time PCR and estimated the redox state of wheat plants infected with different isolates of S. nodorum by spectrometry. The induction of ethylene biosynthesis and signaling has been shown to result from gene-for-gene interaction between Snn3-B1 and SnTox3. The results of plant redox status estimation showed that ethylene inhibited accumulation of hydrogen peroxide in SnTox3-sensitive genotypes by regulating the operation of various pro-/antioxidant enzymes at the transcriptional and posttranslational levels. Our results suggest that NE SnTox3 influences ethylene biosynthesis and signaling, thereby regulating redox metabolism in infected wheat plants as necessary for successful host colonization at the initial phases of infection, which ultimately leads to extensive lesions due to fast pathogen reproduction

The fate of the scientist as a reflection of the epoch: in memory of the first rector of the Kuban State Medical University Nikolai F. Melnikov-Razvedenkov

The paper analyzes the life and professional journey of Nikolai F. Melnikov-Razvedenkov, an outstanding scientist, doctor, and professor, as a reflection of Russian history from the end of the 19th century till the first quarter of the 20th century. The study identifies the role of Nikolai F. Melnikov-Razvedenkov in the development of medical science and the establishment of medical education in the Kuban region. The analysis was conducted with the involvement of archival records, personal correspondence, and scientific works of Nikolai F. Melnikov-Razvedenkov. To solve research problems, the authors used historical descriptive, comparative historical, problem-based chronological, biographical methods, and the method of monographic description. It is shown that the scientist’s fate mirrors the cultural and historical era experienced by the country. The authors define the exclusive role of Nikolai F. Melnikov-Razvedenkov in the establishment of the Kuban Medical Institute. His life path helped reveal the inviolability of medical ethics based on mercy, dedication to the profession, and willingness to serve people. Even in the situation of social upheaval Nikolai F. Melnikov-Razvedenkov found the meaning of his life in scientific work and helping people. His example will allow the modern generation of doctors to gain a greater understanding of the essential purpose of their work

Catechin production in cultured cells of Taxus cuspidata and Taxus baccata

Abstract The main polyphenols in callus and cell suspension cultures of Taxus cuspidata and T. baccata were (?)-catechin and (-)-epicatechin, while lignans, such as (?)-taxiresinol, (?)-isotaxiresinol, (?)-isolariciresinol and (-)-secoisolariciresinol, were present in trace amounts. T. cuspidata cells contained 1.7% (?)-catechin and 2.4% (-)-epicatechin on dry wt basis but when stimulated with methyl jasmonate produced 3.4% catechin and 5.2% epicatechin. These are the highest levels of these metabolites obtained in plant cell cultures

Влияние различных консервантов на состояние роговицы при инстилляции аналогов простагландинов

PURPOSE: Study of the state of the corneal structural components in primary open-angle glaucoma patients on travoprost with the preservative benzalkonium chloride who later switch to the instillation travoprost with preservative polyquad. METHODS: The study included 32 patients (48 eyes) aged 55 to 72 years with primary open-angle glaucoma stage I or II, receiving the drug travoprost containing belzalkonium chloride. This drug has been replaced by travoprost with polyquad, in the same mode of instillation. Along with the standard ophthalmologic examination, patients underwent laser scanning confocal imaging of the cornea. As a result of layer-by-layer confocal laser scanning, we received a series of scans of the cornea with the possibility of observation of each individual layer. Morphology and density of the epithelial and endothelial cells were evaluated, as well as the morphology of the corneal stroma. RESULTS: 8 of the 19 patients presented fewer complaints against foreign body sensation under the eyelids, visual discomfort and idiopathic eye redness after 3 months of instillation travoprost with polyquad, while 11 presented no such complaints at all. After 3 months of using travoprost with polyquad the total number of cells of the corneal epithelium increased from 4723+310 to 6231+415 cells/mm2, in 9 cases corneal epithelial edema decreased, while in 39 of 48 eyes no signs of edema were revealed. The switch to travoprost with polyquad helped reduce the number of keratocytes with bright nuclei and visualized cytoplasmic processes in the surface layers. A statistically non-significant increase in the density of keratocytes in the anterior stroma was observed due to changes in antihypertensive therapy with an average of 634+133 to 987+208 cells/mm2. After applying travoprost with polyquad endothelial cells were well visualized due to epithelium edema reduction and had a hexagonal shape. CONCLUSION: Obtained data showed histomorphological changes in the corneal tissue appearance, associated with long term medicinal therapy with prostaglandin analogue (travoprost with benzalkonium chloride), and the improvement in the state of epithelial front layers and corneal stroma in primary open angle glaucoma patients with a less toxic replacement preservative (travoprost with polyquad).ЦЕЛЬ. Исследовать состояние структурных компонентов роговицы у больных первичной открытоугольной глаукомой на фоне инстилляций травопроста с хлоридом бензалкония и после перевода на травопрост с поликвадом. МЕТОДЫ. Обследованы 32 пациента (48 глаз) в возрасте от 55 до 72 лет с первичной открытоугольной глаукомой I или II стадии, получавших травопрост с хлоридом бензалкония. Этот препарат был заменен на травопрост с поликвадом в том же режиме инстилляций. Наряду со стандартным офтальмологическим обследованием, пациентам проводили исследование роговицы методом лазерной сканирующей конфокальной томографии. В результате послойного конфокального лазерного сканирования мы получали серию сканов роговицы с возможностью наблюдения каждого отдельного слоя. Оценивали морфологию и плотность эпителиальных и эндотелиальных клеток, а также морфологию стромы роговицы. РЕЗУЛЬТАТЫ. У 8 из 19 пациентов выявлено уменьшение жалоб на ощущение инородного тела за веками, дискомфорт при зрительной нагрузке и покраснение глаз без видимой причины после 3 мес. травопроста с поликвадом, у 11 указанные жалобы отсутствовали. После 3 мес. применения травопроста с поликвадом общее количество клеток эпителия роговицы увеличилось с 4723+310 до 6231+415 кл/мм2, в 9 случаях отек эпителия роговицы уменьшился, в 39 из 48 глаз признаков отека не выявляли. Перевод на терапию травопроста с поликвадом способствовал уменьшению количества кератоцитов с яркими ядрами и визуализируемыми цитоплазматическими отростками в поверхностных слоях стромы, наблюдалось статистически незначимое повышение плотности кератоцитов передней стромы в результате изменения гипотензивной терапии в среднем с 634+133 до 987+208 кл/мм2. После применения травопроста с поликвадом клетки эндотелия хорошо визуализировались за счет уменьшения отека эпителия роговицы, имели гексагональную форму. ЗАКЛЮЧЕНИЕ. Полученные данные выявили гистоморфологические изменения ткани роговицы, происходящие на фоне длительной медикаментозной терапии аналогом простагландинов (травопрост с хлоридом бензалкония), и улучшение состояния эпителия и передних слоев стромы роговицы больных первичной открытоугольной глаукомой при замене консерванта на менее токсичный (травопрост с поликвадом)

A relationship between causative agents of infectious diarrhea and fatal outcomes in pre-school children

Infectious diarrhea is one of the leading causes of fatal outcomes in young children. Differential diagnostics of such infections within the first hours of illness poses significant objective obstacles. Data from laboratory studies of autopsy material and pathological studies provide valuable information for understanding the spectrum of differential diagnostics and etiological structure of infectious diarrhea with fatal outcomes in young children. Materials and methods. There were analyzed 100 cases of fatal outcomes in children under the age of six years registered in Russia from November 2011 to December 2019, who was diagnosed with infectious diarrhea at different levels of the healthcare system. The data were assessed based on available medical case reports and the laboratory testing of autopsy samples performed by using nucleic acid amplification methods. Results. The diagnosis of infectious diarrhea was revised in 24 patients, based on the data of a set of intravital and post-mortem studies. In patients with unconfirmed diagnosis of acute intestinal infections, pneumonia was the most often detected — in 45.8% (11/24), sepsis — in 29.2% (7/24), meningitis/meningoencephalitis, acute surgical pathology and asphyxiation associated with vomit aspiration — in 16.7 % (4/24) cases. The causative agents of infectious diarrhea were identified in 71 of 76 patients with confirmed diagnosis of acute intestinal infections. Most prevalent were group A rotaviruses — 52.6% (40/76), group F adenoviruses — 17.1% (13/76), and noroviruses — 13.2% (10/76). Combination of pathogens was detected in 29 cases (38.2%). Prehospital lethal outcomes in patients with infectious diarrhea were observed in 17 cases (22.4%). In total, rate of neonatal deaths due to acute intestinal infections accounted for 62.2% and 2-year-old toddlers — 20.3%. 64 of 76 (84%) children had no unfavorable premorbid background. The most common pathologies associated with infectious diarrhea with developing fatal outcomes were pneumonia (including aspiration pneumonia) in 22.4% (17/76) and aspiration asphyxia in 6.6% (5/76). Hemolytic-uremic syndrome associated with diarrhea was diagnosed in 7.9% (6/76) of children. Conclusions. Within the first years of life children comprise a risk group for developing fatal outcomes during infectious diarrhea. Lack of unfavorable premorbid background should not be considered as a reliable positive prognostic criterion. Diagnostics of pneumonia should be included in the mandatory examination plan for children with severe infectious diar rhea. Based on study of clinical and autopsy material, group A rotaviruses were the lead causative agents among those resulting in infectious diarrhea with fatal outcomes in young children. Special attention should be paid to preventing vomit aspiration within the first days after disease onset

КЛИНИЧЕСКИЙ СЛУЧАЙ СИНДРОМА МИЛЛЕРА - ФИШЕРА В ПРАКТИКЕ ДЕТСКИХ ИНФЕКЦИОННЫХ БОЛЕЗНЕЙ

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КЛИНИЧЕСКИЙ СЛУЧАЙ ГРАНУЛОЦИТАРНОГО АНАПЛАЗМОЗА ЧЕЛОВЕКА НА ТЕРРИТОРИИ АРХАНГЕЛЬСКОЙ ОБЛАСТИ

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Клинико-лабораторные различия у больных с локализованной и генерализованной формами саркомы Капоши

The objective: to evaluate clinical and laboratory parameters in local and generalized forms of Kaposi sarcoma (KS) in HIV infected patients to detect predictors of generalized forms of the disease.Subjects and methods. Case histories of 58 HIV infected patients with KS at the age from 28 to 80 years old were respectively analyzed; they all received treatment in National Medical Research Center of Phthisiopulmonology and Infectious Diseases of the Russian Ministry of Health in 2018-2020. Cases were divided into 2 groups depending on KS manifestations. LF group (local form of KS, n = 28) included the patients with skin lesions; GF group (generalized form of KS, n = 30) included patients with skin lesions and one or several lesions in the other sites: the mucous membrane of gastrointestinal tract, the mucous membrane of tracheobronchial tree, and lung parenchyma.Results. Patients with the generalized form of KS had a higher frequency of skin lesions on the body (pχ2 = 0.036), face (pχ2 = 0.033), and multiple sites (pχ2 = 0.018). Patients from both groups had low CD4+ count, but it was more severe in GF group (pχ2 = 0.027) with a significant increase of the viral load (pχ2 = 0.047). The predictors of the generalized form of KS are the following: the presence of specific lesions on the skin of body, face and multiple localizations, CD4 level below 125 cells/mcL, increase in the viral load above 5.3log10 copies/ml, reduction of erythrocytes level below 3.1 × 1012 cells/L. Among 24 patients with KS who had 4-6 predictors, 19 (79.2%) had the generalized form. Among KS patients with not a single predictor, there were no cases of generalized form, as well as there were no cases of local forms among patients who had 5 and 6 predictors.Цель: оценить клинико-лабораторные параметры при локализованной и генерализованной формах саркомы Капоши (СК) у пациентов с ВИЧ-инфекцией для определения предикторов генерализованных форм заболевания.Материалы и методы. Ретроспективно проанализированы истории болезни 58 пациентов с ВИЧ-инфекцией и СК в возрасте от 28 до 80 лет, получавших лечение в ФГБУ «НМИЦ ФПИ» Минздрава России в 2018-2020 гг. Сформированы две группы в зависимости от проявлений СК. В группу ЛФ (локализованная форма СК, n = 28) включены пациенты с поражением кожи, в группу ГФ (генерализованная форма СК, n = 30) ‒ с сочетанием поражений кожи с одним или несколькими поражениями других локализаций: слизистая оболочка желудочно-кишечного тракта, слизистая оболочка трахеобронхиального дерева, паренхима легких.Результаты. У пациентов с генерализованной формой СК отмечалось увеличение частоты поражения кожи на туловище (pχ2 = 0,036), лице (pχ2 = 0,033), а также множественность локализаций (pχ2 = 0,018). Для пациентов обеих групп было характерно снижение уровня CD4+-лим- фоцитов, но более выраженное в группе ГФ (pχ2 = 0,027) при существенном увеличении вирусной нагрузки (pχ2 = 0,047). Предикторами генерализованной формы СК являются: наличие специфических образований на коже туловища, лица и множественных локализаций, снижение уровня CD4 Т-лимфоцитов ниже 125 кл/мкл, повышение вирусной нагрузки выше 5,3 log10 копий/мл, снижение уровня эритроцитов ниже 3,1 × 1012 кл/л. Среди 24 пациентов с СК, имевших 4-6 предикторов, 19 (79,2%) были с генерализованной формой. Среди пациентов с СК, не имевших ни одного предиктора, случаев генерализованной формы не было, также как не было случаев локализованной формы среди пациентов, имевших 5 и 6 предикторов

Sequelae of COVID-19 at long-term follow-up after hospitalization

Aim. To assess long-term sequelae of COVID-19 in hospitalized patients at 3 to 7 months after discharge.Material and Methods. The whole of 700 patients hospitalized to the temporary COVID-19 treatment center hosted by the FSBI “National Medical Research Center of Cardiology” of the Ministry of Health of Russia from April to June 2020 were invited to participate in a follow-up study. At 3-7 months after the index hospitalization, patients or their proxies were contacted via telephone in order to obtain information on their vital status, cardiovascular and other conditions or their complications, and new hospitalizations. In addition, patients were invited to an outpatient visit under the "COVID-19-follow-up" program, encompassing physical examination and a comprehensive battery of laboratory and instrumental tests, including spirometry, chest computed tomography (CT) and the six minute walk test (6MWT). Further, dyspnea was assessed using the mMRC (Modified Medical Research Council) Dyspnea Scale. Results: We were able to contact 87.4% (612/700) of patients or their proxies. At follow-up, 4.4% (27) patients died, of which 96.3% (26) had cardiovascular diseases (CVD). A total of 213 patients aged 19 to 94 years old (mean age 56.8±12.5, median 57 years [49.0; 64.0]; men, 55.4%) agreed come for an outpatient visit and to participate in the “COVID-19-follow-up” program. Since discharge, 8% (17) of patients required new hospitalizations, and more than a half of these patients (58.8%; 10/17) had CVD-related hospitalizations. A total of 8.4% (18) patients experienced worsening of hypertension, 9 (4.2%) patients had newly diagnosed hypertension, 2 (0.9%) – coronary artery disease patients experienced new/recurrent angina symptoms. 4 (1.9%) patients had newly diagnosed coronary artery disease, and one patient had an ischemic stroke. At the outpatient visit, 114 (53.5%) patients had some symptoms, most frequently, shortness of breath (33%), fatigue (27.4%), chest pain (11.3%), and abnormal heartbeats (8.5%). Based on the mMRC Scale, 59% of patients had dyspnea of varying severity. Most patients had a normal vital capacity (VC), which was moderately reduced in 3.3% and severely reduced in 0.5% of patients. Chest CT scans were obtained in 78 (36.6%) patients, whose worst lung damage scores during hospitalization were CT3 or CT4. One in ten patients (10.8%) with severe lung damage during acute infection had persisting ground glass opacities, 35.9% developed fibrotic changes, 79.6% of patients had linear or fine focal opacities. According to the 6MWT data, 12.3% of patients walked less than 70% of the predicted distance, 67% walked 71 to 99% of the predicted distance, and 20.7% of patients were able to walk 100% of their predicted distance.Conclusion. These data suggest long-term negative sequelae of COVID-19 in more than half of hospitalized patients