Comparing the effects of surgical treatment and chemotherapy on the thymus structure in experimental breast cancer

Цель исследования - выявление структурных преобразований тимуса самок крыс Вистар при хирургическом лечении рака молочной железы и при химиотерапии. Методика. Рак молочной железы (РМЖ) индуцировали введением N-метил-N-нитрозомочевины 5 раз с интервалом 7 сут подкожно в область 2-й молочной железы справа. Оперативное лечение РМЖ проводили через 6 мес от момента индукции РМЖ. Курс химиотерапии проводили по схеме CMF. Гистологическое исследование тимуса и опухоли молочной железы проводили по стандартной методике. Методом точечного счёта производили морфометрию срезов и подсчет клеточных элементов в опухоли и структурно-функциональных зонах тимуса. Результаты. При РМЖ без лечения выявлены структурные признаки акцидентальной инволюции тимуса. После оперативного лечения РМЖ акцидентальная инволюция тимуса менее выражена по сравнению с химиотерапией. После оперативного лечения РМЖ, как и в группе РМЖ без лечения, в тимусе сохраняется уменьшение площади коркового вещества. По сравнению с РМЖ без лечения в тимусе уменьшалась площадь железистых эпителиальных образований, увеличилась плотность расположения клеточных элементов в корковом веществе. В структурных зонах тимуса увеличивалось количество макрофагов, снижалось количество клеток с пикнотичными ядрами. После химиотерапии, по сравнению с резекцией опухоли МЖ, в тимусе выявлены структурные признаки прогрессирования процесса инволюции. В тимусе уменьшена площадь соединительно-тканных элементов, снижено количество митозов в субкапсулярной зоне коркового вещества. Во всех исследуемых зонах увеличено количество клеток с пикнотичными ядрами и уменьшено число макрофагов. Заключение. После оперативного лечения РМЖ акцидентальная инволюция тимуса проявляется в менее выраженной форме, чем в группе с РМЖ без лечения. После химиотерапии РМЖ, по сравнению с оперативным лечением РМЖ, морфологические перестройки в тимусе свидетельствуют о снижении активности лимфоидного и эпителиального компонентов и увеличении числа гибнущих клеток. Aim. To identify structural changes in the thymus of female Wistar rats during surgical treatment of breast cancer or with chemotherapy. Methods. Breast cancer (BC) was induced by subcutaneous injection of N-methyl-N-nitrosourea into the second right breast 5 times at 7 day intervals. Resection of BC was performed 6 mos after BC induction, or chemotherapy was administered according to the CMF scheme. Histological examination of the thymus and breast tumor was performed according to a standard method. Morphometric study of sections and counting cell elements in the tumor and in structural and functional areas of the thymus were performed by point counting. Results. In untreated BC, structural signs of accidental thymus involution were evident. There was an increase in the area of connective tissue elements and of glandular epithelial tumors. After surgical treatment of BC, accidental thymus involution was less pronounced than after chemotherapy. Also after surgical treatment, as in the case of untreated BC, the thymus cortical substance remained decreased. Compared with untreated BC, the area of glandular epithelial tumors in the thymus decreased, and the density of cellular elements in the cortical substance increased. In the structural zones of the thymus, the number of macrophages increased, and the number of cells with pyknotic nuclei decreased. After chemotherapy, in comparison with surgical treatment, structural signs of involution of the thymus were evident. In the thymus, the area of connective tissue elements was reduced, and the number of mitotically dividing cells in the subcapsular zone of the cortical substance was reduced. In all the zones of the thymus, the number of cells with pyknotic nuclei increased, and the number of macrophages decreased. Conclusion. After surgical treatment of BC, accidental thymus involution was less pronounced than in the untreated group. After chemotherapy, compared with surgical treatment of BC, morphological changes in the thymus may indicate a decrease in the activity of the lymphoid and epithelial components and an increase in the number of dying cells.

miR-199b-5p enhances the proliferation of medullary thymic epithelial cells via regulating Wnt signaling by targeting Fzd6

Thymic epithelial cells (TECs) are essential regulators of T-cell development and selection. miRNAs play critical roles in regulating TEC proliferation during the process of thymic aging. Our previous studies revealed that miR-199b-5p was upregulated in TECs from 1- to 3-month-old mice. But its function and potential mechanism are not clear. We hypothesized that miR-199b-5p may play an important role in age-related thymus involution via targeting some genes. To confirm it, the murine thymic epithelial cell line 1 (MTEC1) cells were used. Our results showed that overexpression of miR-199b-5p can enhance MTEC1 cell proliferation. On the contrary, repression of miR-199b-5p can inhibit MTEC1 cell proliferation. Meanwhile, it was confirmed that frizzled receptor 6 (Fzd6) is the direct target gene of miR-199b-5p. Furthermore, overexpression of miR-199b-5p can upregulate the expressions of β-catenin, Tcf7, Wnt4, and C-myc to activate Wnt signaling and cell cycle signaling. Silence of Fzd6 and co-transfection with siFzd6 and miR-199b-5p mimic/inhibitor confirmed that the biological function of miR-199b-5p is indeed by targeting Fzd6 in medullary TECs. Overall, miR-199b-5p is an important regulator in medullary TEC proliferation through targeting Fzd6 to activate Wnt signaling and cell cycle signaling. Our data indicate that miR-199b-5p may block the process of thymic aging and be a potential therapeutic target for thymus involution.

INFLUENCE OF BIOLOGICAL STIMULATOR NUCLEOSTIM ON CENTRAL IMMUNITY BODIES IN BROILER CHICKENS

Poultry farming is one of the most important dynamically developing branches of the agro-industrial complex, providing the population with fullfledged food products. It is necessary to search for new useful biological substances to increase the efficiency of the industry. At the same time, biologically active substances must be not only highly effective but also harmless to animals and humans. To date, significant experimental data on the use of biological stimulants in poultry and animal husbandry have been accumulated. The research aimed to study the influence of the biological stimulator Nucleostim on the development of the thymus and its clinical and morphological structure. 100 ROSS 308 cross broiler chickens were used for the research. Experimental and control groups of animals were kept in the same conditions on a unique, balanced diet with free access to water. In the course of the research, it was found that in 3 experimental groups, the mass of internal organs of broiler chickens is greater than in the control group. The most significant increase in organs was observed in chickens receiving Nucleostim at a dose (10 g/kg of feed). The use of the biological stimulator Nucleostim as a top dressing in broiler chickens preserves the structure of the thymus, with clear visualization and differentiation of the cortical layer and brain matter, increases the mitotic activity of thymocytes, improves blood supply to the organ. As a result of research, it was found that Nucleostim has an immunomodulatory effect, which is expressed in hypertrophy and hyperplasia of the thymus, increasing the number of CD 68 macrophages, slowing down the thymus involution processes in broiler chickens.

Mikronährstoffe, Immunüberwachung und Immunseneszenz

ZusammenfassungWie andere Organsysteme ist auch das komplexe und dezentrale Immunsystem dem Alterungsprozess unterworfen. Dies zeigt sich teilweise auf Organebene (z. B. Thymus-Involution) als auch auf zellulärer und molekularer Ebene. Zu den Kennzeichen des Alterns zählt auch die Verringerung an Stammzellen, die sich besonders im Immunsystem bemerkbar macht. Durch die bereits bei der Verlängerung der Lebensspanne erzielten Fortschritte wird das Immunsystem in höherem Alter umso stärker belastet; dies begleitet die Entstehung altersassoziierter Erkrankungen wie etwa Krebs. Allein schon ein Ausgleich von Mikronährstoff-Defiziten kann eine Immunregeneration bewirken. Die Rolle von Mikronährstoffen in der Immunabwehr von Infektionen und der Bekämpfung von Krebserkrankungen wird besprochen und v. a. die Rolle von Vitamin D, Zink und Selen diskutiert. Erste Hinweise zeigen, dass in Zeiten einer Viruspandemie einer solchen Unterstützung des Immunsystems von Patienten erhebliche Bedeutung zukommt.