Галектины 1 и 3 в механизмах рекрутирования эозинофильных гранулоцитов в опухолевую ткань при раке желудка и толстого кишечника

Background: Gastric and colon tumors are often associated with eosinophilic infiltration of tumor tissue, the significance of which is still not entirely clear. The recruitment of eosinophils into the tissues can be in part regulated by galectins ― galactose-binding proteins which are expressed by a variety of tissues and are capable of exerting a broad range of effects. Aims: To evaluate the expression of galectin-1 and galectin-3 in tumor tissue, and gal-3 gene mRNA expression in blood eosinophils in patients with gastric and colon cancer with or without tissue eosinophilia. Materials and methods: The study included a total of 107 patients (84 males and 23 females, average age 60,9 6,8) with verified gastric cancer (52 persons) and colon cancer (55 persons), who underwent treatment or were registered at the dispensary at the regional medical institution Tomsk Regional Oncology Center (Tomsk, Russia). The control group consisted of 15 men and 11 women of comparable age. The materials of the research included samples of gastric and colon tumors obtained during surgery, and eosinophilic granulocytes isolated from whole blood by immunomagnetic separation. Galectin-1 and galectin-3 expression in tumor tissue was evaluated by immunohistochemistry. The expression of gal-3 gene mRNA in eosinophils was determined by real-time reverse transcription polymerase chain reaction. Statistical analysis of the results was carried out using the non-parametric Mann-Whitney U test for independent samples with Benjamini-Hochberg procedure for multiple comparisons, and the Chi-square Pearson criterion with Yates correction. Results: In patients with gastric cancer and colon cancer, regardless of the presence of tissue eosinophilia, low expression of galectin-3 in the tumor tissue and high expression of gal-3 gene mRNA in peripheral blood eosinophils were found. Gastric and colon cancer patients with eosinophilic infiltration of tumor tissue were characterized by low expression of galectin-1 within tumor cells (in 64.0% cases, 2 = 4.890, р = 0.029; and in 73.9% cases, 2 = 5.981, p = 0.031 respectively). There was a statistically significant connection between the level of galectin-1 expression by tumor cells and the presence of tissue eosinophilia both in gastric ( = 0.307) and colon cancer ( = 0.330). Conclusion: Low expression of galectin 1 and 3 by tumor cells in gastric and colon cancer with tissue eosinophilia indicates the lack of a significant effect of these proteins on the process of recruiting eosinophilic granulocytes into tumor tissue. Increased expression of galectin-3 in blood eosinophils in gastric and colon cancer is not associated with the presence of eosinophilic infiltration of tumor tissue.Обоснование. При раке желудка и толстого кишечника весьма часто обнаруживается эозинофильная инфильтрация опухолевой ткани, значение которой до сих пор неясно. В регуляции рекрутирования эозинофилов в ткань новообразования принимают участие галектины ― белки, экспрессируемые многими клетками и характеризующиеся широким спектром свойств. Цель исследования ― оценить экспрессию галектинов 1 и 3 в опухолевой ткани и м-РНК гена галектина-3 в эозинофилах крови при раке желудка и толстого кишечника с тканевой эозинофилией и без нее. Методы. Обследованы 107 пациентов (84 мужчины и 23 женщины, средний возраст 60,9 6,8 лет) с верифицированным диагнозом рака желудка (52 больных) и рака толстого кишечника (55 больных), которые проходили лечение в ОГАУЗ Томский областной онкологический диспансер (Томск). В группу контроля вошли 15 мужчин и 11 женщин сопоставимого возраста. Материал исследования: эозинофильные гранулоциты, выделенные из цельной крови методом иммуномагнитной сепарации, и образцы опухолевой ткани желудка и толстого кишечника, полученные в ходе оперативного вмешательства. Экспрессию галектинов 1 и 3 в опухолевой ткани оценивали методом иммуногистохимии. Исследование экспрессии м-РНК гена галектина-3 в эозинофильных гранулоцитах осуществляли методом полимеразной цепной реакции в режиме реального времени с использованием обратной транскрипции. Для статистической обработки результатов применяли непараметрический U-критерий МаннаУитни для независимых выборок с поправкой БенджаминиХохберга для множественного сравнения и критерий хи-квадрат Пирсона с поправкой Йейтса. Результаты. У пациентов с раком желудка и раком толстого кишечника вне зависимости от наличия тканевой эозинофилии установлена низкая экспрессия галектина-3 в опухолевой ткани и, напротив, высокий уровень экспрессии м-РНК гена галектина-3 в эозинофильных гранулоцитах периферической крови. У больных раком желудка и раком толстого кишечника с тканевой эозинофилией зарегистрирована низкая экспрессия опухолевыми клетками галектина-1 (в 64,0% случаев, 2 = 4,890, р = 0,029, и в 73,9% случаев, 2 = 5,981, p = 0,031 соответственно). Показана ассоциация гипоэкспрессии галектина-1 с эозинофильной инфильтрацией злокачественных опухолей желудка ( = 0,307) и толстого кишечника ( = 0,330). Заключение. Дефицит экспрессии галектинов 1 и 3 в опухолевой ткани при раке желудка и толстого кишечника, сопровождающийся тканевой эозинофилией, свидетельствует об отсутствии значимого влияния данных белков на процесс рекрутирования эозинофильных гранулоцитов в опухолевую ткань. Повышенный уровень экспрессии галектина-3 эозинофилами крови при злокачественных опухолях желудка и толстого кишечника не зависит от наличия эозинофильной инфильтрации опухолевой ткани

Inferring HIV-1 transmission networks and sources of epidemic spread in Africa with deep-sequence phylogenetic analysis

To prevent new infections with human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa, UNAIDS recommends targeting interventions to populations that are at high risk of acquiring and passing on the virus. Yet it is often unclear who and where these ‘source’ populations are. Here we demonstrate how viral deep-sequencing can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks. We are able to deep-sequence virus from a large population-based sample of infected individuals in Rakai District, Uganda, reconstruct partial transmission networks, and infer the direction of transmission within them at an estimated error rate of 16.3% [8.8–28.3%]. With this error rate, deep-sequence phylogenetics cannot be used against individuals in legal contexts, but is sufficiently low for population-level inferences into the sources of epidemic spread. The technique presents new opportunities for characterizing source populations and for targeting of HIV-1 prevention interventions in Africa

Autoresonance phenomenon in a long mirror

The paper describes an implementation of a long mirror-based variant of cyclotron autoresonance which permits a local temporary change in the mirror`s induction and provides a mode for filling the trap with primary plasma, and for the generation of plasma bunches with an energetic electron component and their accumulation within a single cavity. The approach does not require injection of external particles into the acceleration zone as particles can be generated directly within the mirror using specialized conditions of electron cyclotron resonance (ECR) as part of the operational mode. A detailed study of the spectral-angular distribution of Bremsstrahlung in various operational modes has been undertaken. The results of this study permit the optimal value of the time sequence between the leading edge of the pulsed magnetic field and the microwave pulse to be determined, which ensures the optimal mode of electron trapping in the cyclotron autoresonance mode. Bremsstrahlung radiation recorded in the transverse direction has a significantly higher intensity of photons and energy compared to the longitudinal direction during the acceleration and subsequent confinement mode of plasma bunches. The observed changes in the intensity and spectral distribution of the Bremsstrahlung, which depend on the values of the operating parameters for acceleration, afford the possibility to define the dependence of the number of initial plasma particles trapped by cyclotron autoresonance for the different operating modes. The results will improve our understanding of the processes taking place at various stages of the operational modes. In general, such studies are important for gaining an improved understanding of the mechanisms of generation and confinement of hot electron plasma bunches with an energetic electron component for autoresonant interaction in a long mirror. © 2021 Author(s)

Evolution of energy spectra of the electronic component for plasmoids generated under autoresonance conditions in a long magnetic mirror

We performed a 3D numerical simulation of plasmoid generation with a relativistic electron component under gyromagnetic autoresonance conditions in a long mirror trap. We studied the process of plasmoid formation, the spaciotemporal dynamics and the evolution of the energy spectra of the electron component of the plasma and the efficiency of electron trapping as a function of the experimental parameters. © 2018 Institute of Physics Publishing. All rights reserved

Parameters of plasma bunches generated in a long mirror trap under conditions of gyromagnetic autoresonance

Temporal evolution of the spectrum and intensity of bremsstrahlung generated by the plasma bunches formed in a symmetric long mirror trap under conditions of gyromagnetic autoresonance was studied experimentally in detail. Bremsstrahlung was detected by two identical detectors installed in the axial and radial directions with respect to the stationary magnetic field. The results show that the radiation is spatially inhomogeneous. The parameters of the spectra measured in the radial direction strongly depend on the amplitude of the pulsed magnetic field, while the spectra measured in the longitudinal direction are determined mainly by the ECR conditions in the phase of filling the trap with the primary plasma. The integrated intensities, obtained with allowance for the refined form factors of the generated bunches recorded using the high-speed photochronography, made it possible to determine the number of primary plasma particles trapped in the autoresonance mode. © 2019 Published under licence by IOP Publishing Ltd

Spectral changes of bremsstrahlung plasma bunch generated under autoresonance in a long mirror

In this study, different scenarios of gyromagnetic autoresonance (GA) in a reverse magnetic field of a long mirror trap were realized. A detailed study of the spectral-angular distribution of X-Ray radiation (XR) in various experimental modes was conducted. The experimentally observed temporal behavior of the XR confirmed the modeling results of the dynamics of the generated plasma bunches with an energetic electron component, both in the GA phase and in the confinement mode. © 2018 Institute of Physics Publishing. All rights reserved

Photochronological, radiographic, and modeling studies of dynamics of the development of relativistic plasma formations in the length mirror cells

The work presents experimental results showing the feasibility of autoresonance acceleration in the reverse magnetic field in an extended trapped in the mirror type. It has been shown that electron bunches are formed as a result of the gyromagnetic autoresonance. They have an average energy of several hundred keV and trapped for a long time in the mirror. The results obtained by a computer simulation of the GA reverse mode agree completely with the experimental data

Spatial distribution of a plasma vortex obtained under gyromagnetic resonance in the mirror magnetic trap

The spatial configuration of a plasma vortex with the middle relativistic electron component produced under the gyromagnetic autoresonance and confined in the mirror magnetic trap have been studied experimentally and by numerical modeling using a particle in the cell method. Characteristics of bremsstrahlung generated by the plasma vortex on gas and chamber walls were investigated by the X-ray spectrometry and radiometry methods. Obtained results and their analysis have allowed to define the vortex localization and dynamics. The sizes of the bunch: the radius is 2 cm; the size along the axis is about 0.5 cm. The number of electrons trapped in gyromagnetic autoresonance mode is 50-70 percent of the number of electrons in the initial plasma

Study of the development of relativistic plasma bunches in a long mirror trap by optical and X-ray imaging and numerical simulations

The work presents experimental results demonstrating the feasibility of autoresonance acceleration of electrons in a long mirror trap with a reverse magnetic field. It is shown that gyromagnetic autoresonance results in the formation of a plasma bunch with average electron energy of several hundred keV, which is confined for a long time in the trap. The results of computer simulations of the regime of reverse gyromagnetic autoresonance agree well with the experimental data. © 2017, Pleiades Publishing, Ltd

Properties and parameters of the electron beam injected into the mirror magnetic trap of a plasma accelerator

The parameters of the injector of an axial plasma beam injected into a plasma accelerator operating on the basis of gyroresonance acceleration of electrons in the reverse magnetic field are determined. The trapping of the beam electrons into the regime of gyroresonance acceleration is numerically simulated by the particle- in-cell method. The optimal time of axial injection of the beam into a magnetic mirror trap is determined. The beam parameters satisfying the condition of efficient particle trapping into the gyromagnetic autoresonance regime are found. © 2016, Pleiades Publishing, Ltd