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

Comparative investigations of structure and properties of micro-arc wollastonite-calcium phosphate coatings on titanium and zirconium-niobium alloy

Investigation results of micro-arc wollastonite–calcium phosphate (W–CaP) biocoatings on the pure titanium (Ti) and Zr–1wt.%Nb (Zr–1Nb) alloy were presented. The voltages of 150–300 V generate the micro-arc oxidation (MAO) process with the initial amplitude current of 150–550 A and 100–350 A for Ti and Zr–1Nb substrates, respectively. The identical dependencies of changes of the coating thickness, surface roughness and adhesion strength on the process voltage were revealed for the both substrates. The W–CaP coatings with the thickness of 10–11 μm were formed on Ti and Zr–1Nb under the low process voltage of 130–150 V. Elongated wollastonite particles with the size in the range of 40–100 μm were observed in such coatings. The structure of the coatings on Ti was presented by the X–ray amorphous and crystalline phases. The X–ray reflexes relating to the crystalline phases of Ti and wollastonite were observed only in XRD patterns of the coatings deposited under 130–200 V on Ti. While, the crystalline structure with phases of CaZr4(PO4)6, β–ZrP2O7, ZrO2, and Zr was detected in the coatings on Zr–1Nb. FT–IRS, XRD, SEM, and TEM data confirmed that the increase of the process voltage to 300 V leads to the dissociation of the wollastonite. No toxic effect of specimens on a viability, morphology and motility of human adipose–derived multipotent mesenchymal stem cells was revealed in vitro

Effect of the deuterium on efficiency and type of adipogenic differentiation of human adipose-derived stem cells in vitro

In this study, we performed an adipogenic differentiation of human adipose-derived stem cells (ADSCs) in vitro with different deuterium content (natural, low and high) in the culture medium during differentiation process with parallel analysis of the gene expression, metabolic activity and cell viability/toxicity. After ADSCs differentiation into adipocytes we have done the analysis of differentiation process efficiency and determined a type of resulting adipocytes (by morphology, gene expression, UCP1 protein detection and adipokine production analysis). We have found that high (5 × 105 ppm) deuterium content significantly inhibit in vitro adipogenic differentiation of human ADSCs compared to the groups with natural (150 ppm) and low (30 ppm) deuterium content. Importantly, protocol of differentiation used in our study leads to white adipocytes development in groups with natural (control) and high deuterium content, whereas deuterium-depleted differentiation medium leads to brown-like (beige) adipocytes formation. We have also remarked the direct impact of deuterium on the cellular survival and metabolic activity. Interesting, in deuterium depleted-medium, the cells had normal survival rate and high metabolic activity, whereas the inhibitory effect of deuterated medium on ADSCs differentiation at least was partly associated with deuterium cytotoxicity and inhibitory effect on metabolic activity. The inhibitory effect of deuterium on metabolic activity and the subsequent decrease in the effectiveness of adipogenic differentiation is probably associated with mitochondrial dysfunction. Thus, deuterium could be considered as an element that affects the substance chirality. These findings may be the basis for the development of new approaches in the treatment of obesity, metabolic syndrome and diabetes through the regulation of adipose-derived stem cell differentiation and adipocyte functions. © 2020, The Author(s)