STRUCTURAL TRANSFORMATIONS IN AXILLARY AND MESENTERIC LYMPH NODES IN CHEMOTHERAPY AND SURGICAL TREATMENT OF EXPERIMENTAL MAMMARY TUMOR

Was conducted histological study axillary and mesenteric lymph nodes in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil), operative removal of breast tumors (6.5 months from the beginning of the experiment). The results of the study. At chemotherapy of breast cancer, compared with the group with breast cancer without treatment, there was a decrease in the number of tumor cells in the axillary lymph nodes in comparison with mesenteric lymph nodes. The decrease in the area of the paracortical zone and the area of secondary lymphoid nodes remain in the axillary lymph nodes, in comparison with breast cancer without treatment. The reduction of the paracortical zone square remains in mesenteric lymph nodes. The area of lymphoid nodules with germinative centers decreases. The number of postcapillary venules with high endothelium and the number of macrophages in structural zones grow down. In the axillary lymph nodes after surgical treatment of breast cancer and chemotherapy in comparison with the treatment of breast cancer only with cytostatics, there is decrease in the area of the paracortical zone (with an increase in the number of small lymphocytes) and medullare cords. The area of lymphoid nodules with germinative and without germinative centers increases. In mesenteric lymph nodes, drainage function is reduced, increased the area of the paracortical zone, reduced the areas of lymphoid nodules with germinative centers and medullare cords (increased proliferative activity of cells), macrophage reaction in the cortical substance was revealed. Conclusion. The severity of structural transformations in cytoarchitectonics of the axillary and mesenteric lymph nodes depends on the treatment method

CORRELATION BETWEEN CYTOKINE CONTENT IN LYMPH OF THORACIC LYMPH DUCT AND MESENTERIC LYMPH NODE STRUCTURAL TRANSFORMATIONS IN EXPERIMENTAL MAMMARY TUMOR AND CHEMOTHERAPY

The aim of the study was to fulfill correlation analysis of morphometry of the mesenteric lymph nodes and the concentration of cytokines in the lymph of the thoracic duct in breast cancer induced by intramammary administration of N-methyl-N-nitrosourea, chemotherapy according to the CMF scheme (cyclophosphamide, methotrexate, 5-fluorouracil). The results of the study. At breast cancer revealed positive correlation: in the germinative centers and medullary cords of cytokine IL-5 with mitotically dividing cells, chemokines MIP-1α with average lymphocytes, in the germinative centers of immunoblasts with cytokine GRO/KC, in the paracortical zone chemokine MCP-1 with macrophages, reticular cells with IL-6 and M-CSF, in the medullary sinuses chemokine GRO/KC with small lymphocytes and mature plasma cells (number which decreases). All this may indicate the activity of the local immune response in the lymph nodes aimed on the antitumor protection. After chemotherapy of breast cancer, compared with breast cancer without treatment, revealed positive relationship, which may indicate increased immunomodulatory and antitumor actions of cytokines: correlation of interferon IFNγ with small lymphocytes (number which increased) and macrophages in the germinative centers and mitotically dividing cells in the medullary cords, correlation in the germinative centers of immunoblasts with MIP-1α and increased of number small lymphocytes in T-dependent zone lymph nodes, correlation in medullary cords of interleukin IL-17 with mature plasma cells (number which increased) , correlation of interleukin IL-18 with mature plasma cells in medullary sinuses. Conclusion. Study of the correlation of the concentration of cytokines in the lymph of the thoracic duct with structural changes in the mesenteric lymph nodes revealed dependencies aimed at increasing the immunomodulating and antitumor effects of cytokines

УРОВНИ ГОРМОНОВ, микроРНК И ЦИТОКИНОВ В ЛИМФЕ В НОРМЕ И ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫ В ЭКСПЕРИМЕНТЕ

The involvement of hormones, microRNAs and cytokines in breast cancer pathogenesis has been well established. Lymph picks up secretory products of breast cancer cells. The purpose of the study was to evaluate the levels of hormones, microRNAs and cytokines in lymph. Wistar rats were injected with N-methyl-N-nitrosourea to induce breast cancer. The rats were subjected to either surgery alone or chemotherapy alone (cyclophosphamide, methotrexate and 5-fluorouracil). In some animals, surgery was followed by chemotherapy. The levels of follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH), estradiol (E2) and thyroglobulin (TG), microRNA-21, microRNA-221, microRNA-222, microRNA-429 and 24 cytokines were determined. Chemotherapy was shown to result in the reduction in the levels of prolactin, thyroglobulin, FSH and estradiol. In rats with breast cancer, the expression levels of microRNA-21, microRNA-221 and microRNA-222 were increased, and the expression levels of microRNA-429 were decreased. In breast cancer rats, the levels of most cytokines were found to be increased. Correlations between the levels of cytokines, hormones, and microRNAs in lymph were identified. Differences in the expression levels of cytokines, hormones, and microRNAs in lymph with respect to treatment option were detected.Цель исследования – оценка уровней гормонов, микроРНК и цитокинов в лимфе.Материал и методы. Экспериментальный рак молочной железы индуцировали введением N-метил-N-нитрозомочевины у крыс Wistar. Часть животных подвергалась только оперативному вмешательству или только химиотерапии (циклофосфан, метотрексат, 5-фторурацил). У части животных сочетали оперативное вмешательство с последующим курсом ХТ. В лимфе исследовали содержание фолликулостимулирующего гормона (ФСГ), пролактина, лютеинизирующего гормона (ЛГ), эстрадиола (Е2) и тириоглобулина (ТГ), микроРНК-21, микроРНК-221, микроРНК-222, микроРНК-429 и 24 цитокинов.Результаты. Показано, что на фоне ХТ снижаются уровни пролактина, тиреоглобулина, ФСГ и эстрадиола. В группе животных с РМЖ увеличены уровни экспрессии микроРНК-21, микроРНК-221, микроРНК-222 и снижены уровни экспрессии микроРНК-429. При РМЖ в лимфе увеличены уровни большинства цитокинов. Между уровнями в лимфе цитокинов, гормонов и микроРНК определены взаимосвязи. В лимфе выявляются различные уровни цитокинов, гормонов и микроРНК с учетом вида проведенного лечения

Опухоль-ассоциированные мезенхимные стволовые клетки при химически-индуцированном раке молочной железы у крыс Wistar

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies.Цель исследования – сравнить морфофункциональные свойства мезенхимных стволовых клеток из тканей молочной железы и ткани химически-индуцированной опухоли молочной железы. материал и методы. У 20 крыс-самок Wistar после синхронизации эструса хорионическим гонадотропином, интрамаммарным введением N-метил-N-нитрозомочевины индуцирована аденокарцинома молочной железы, контрольную группу составили 5 крыс. Верификацию опухоли проводили гистологически и иммуногистохимически. Принадлежность выделенных клеток из ткани молочной железы и опухоли молочной железы к мезенхимным стволовым клеткам верифицировали на основании морфологии и фенотипирования на проточном цитофлуориметре FACS Canto II. Функциональные свойства мезенхимных стволовых клеток оценивали в МТТ-тесте и по уровню продукции оксида азота в норме и при индукции перекисью водорода окислительного стресса. Уровни пролактина, лютеинизирующего гормона и эстрадиола Е2 в моче исследовали твердофазным иммуноферментным анализом. Результаты. Химически индуцированная опухоль молочной железы по данным гистологического и иммуногистохимического исследования соответствовала люминальному В1 типу рака молочной железы у человека. Уровни пролактина в моче после синхронизации эструса у животных с развившейся опухолью были повышены, а у животных с неразвившейся опухолью молочной железы снижены уровни пролактина и лютеинизирующего гормона, но повышены уровни эстрадиола Е2. Из ткани опухоли молочной железы получено большее количество мезенхимных стволовых клеток с фенотипом CD45-/CD90+. Мезенхимные стволовые клетки из ткани опухоли проявляли повышенный пролиферативный потенциал и были более устойчивы к окислительному стрессу. заключение. Из ткани химически индуцированной опухоли молочной железы получены опухоль-ассоциированные мезенхимные стволовые клетки, которые имеют высокий пролиферативный потенциал и устойчивы к окислительному стрессу. Выявленные морфофункциональные различия мезенхимных стволовых клеток из тканей молочных желез и ткани опухоли молочной железы требуют дальнейшего исследования

The effects of material formulation and manufacturing process on mechanical and thermal properties of epoxy/clay nanocomposites

A holistic study was conducted to investigate the combined effect of three different pre-mixing processes, namely mechanical mixing, ultrasonication and centrifugation, on mechanical and thermal properties of epoxy/clay nanocomposites reinforced with different platelet-like montmorillonite (MMT) clays (Cloisite Na+, Cloisite 10A, Cloisite 15 or Cloisite 93A) at clay contents of 3–10 wt%. Furthermore, the effect of combined pre-mixing processes and material formulation on clay dispersion and corresponding material properties of resulting composites was investigated using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), flexural and Charpy impact tests, Rockwell hardness tests and differential scanning calorimetry (DSC). A high level of clay agglomeration and partially intercalated/exfoliated clay structures were observed regardless of clay type and content. Epoxy/clay nanocomposites demonstrate an overall noticeable improvement of up to 10 % in the glass transition temperature (Tg) compared to that of neat epoxy, which is interpreted by the inclusion of MMT clays acting as rigid fillers to restrict the chain mobility of epoxy matrices. The impact strength of epoxy/clay nanocomposites was also found to increase by up to 24 % with the addition of 3 wt% Cloisite Na+ clays. However, their flexural strength and hardness diminished when compared to those of neat epoxy, arising from several effects including clay agglomeration, widely distributed microvoids and microcracks as well as weak interfacial bonding between clay particles and epoxy matrices, as confirmed from TEM and SEM results. Overall, it is suggested that an improved technique should be used for the combination of pre-mixing processes in order to achieve the optimal manufacturing condition of uniform clay dispersion and minimal void contents

Transient Ureteral Obstruction Prevents against Kidney Ischemia/Reperfusion Injury via Hypoxia-Inducible Factor (HIF)-2α Activation

Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure

Recent trends in the use of electrical neuromodulation in Parkinson's disease

Purpose of Review: This review aims to survey recent trends in electrical forms of neuromodulation, with a specific application to Parkinson’s disease (PD). Emerging trends are identified, highlighting synergies in state-of-the-art neuromodulation strategies, with directions for future improvements in stimulation efficacy suggested. Recent Findings: Deep brain stimulation remains the most common and effective form of electrical stimulation for the treatment of PD. Evidence suggests that transcranial direct current stimulation (tDCS) most likely impacts the motor symptoms of the disease, with the most prominent results relating to rehabilitation. However, utility is limited due to its weak effects and high variability, with medication state a key confound for efficacy level. Recent innovations in transcranial alternating current stimulation (tACS) offer new areas for investigation. Summary: Our understanding of the mechanistic foundations of electrical current stimulation is advancing and as it does so, trends emerge which steer future clinical trials towards greater efficacy