Pathomorphological, immunohistochemical, and morphometric studies were performed on samples of coronary, common carotid, renal, and common iliac arteries from 32 patients (95 samples) who died at the age of 40-70 years without terminal atherosclerosis (vascular stenosis < 35

A morphological and immunohistochemical analyses of the liver of male WAG rats (n=47) were performed after isolated and combined administration of doxorubicin and rosuvastatin. Doxorubicin (7 mg/kg) was administered intraperitoneally once, while rosuvastatin (10 mg/kg) was given intragastrically daily; the animals were euthanized after 4, 14, and 21 days of experiment. The main morphological changes observed in the liver after both isolated doxorubicin administration and in combination with rosuvastatin included dystrophic and necrobiotic changes in hepatocytes, uneven congestion with the formation of thrombotic masses in the portal vein system, and pronounced perivenous edema. Isolated administration of rosuvastatin led to severe dystrophic changes in hepatocytes and fewer circulatory disturbances in the form of vascular congestion. Immunohistochemical analysis revealed nuclear, cytoplasmic, and mixed (nuclear-cytoplasmic) localization of HSP70 in hepatocytes in all experimental groups. In the liver of control rats, mixed localization of HSP70 significantly prevailed (>62% of hepatocytes; p<0.001); only nuclear localization was found in 9% of cells. When doxorubicin and rosuvastatin were administered alone or in a combination, significant translocation of HSP70 from the cytoplasm to the nucleus occurred (the index of hepatocytes with HSP70 localization in the nuclei increase by 3-4.5 times), which may reflect the cytotoxic nature of these drugs and the activation of cytoprotective mechanisms.

Structural changes in rat hepatocyte nucleoli were studied during deep hypothermia simulated by immersion in water at 5°C for 40 min (ambient air temperature 7°C). In comparison with the control, phenomena of nucleolar stress occurred in rats during hypothermia: the number of fibrillar centers (FC) per nucleus (by 1.7 times) and per nucleolus (by 1.6 times), nucleolonemal nucleoli per nucleus (by 2.8 times), and the relative content of nucleolonemal nucleoli per nucleus (by 2.6 times) significantly decreased (p=0.0000001); the number of FC per nucleolonemal nucleolus also decreased by 1.4 times (p=0.01). In the hepatocyte nuclei, we observed an increase in the relative content of transitional type nucleoli per nucleus (by 1.3 times; p=0.01), the number of FC per transitional type nucleolus (by 1.4 times; p=0.003), the content of free FC per nucleus (by 3 times; p=0.00004), and the percentage of free FC per nucleus (by 3.5 times; p=0.00004). These changes can be considered as compensatory and adaptive reactions, and transitional type nucleoli can be attributed to the "reserve" nucleolar pool.

The association of clinical, pathological, and immunohistochemical characteristics of papillary thyroid cancer with cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center. According to multivariate analysis, the independent predictors of fatal outcome within 10 years after surgery in patients living in Altai region are nuclear pattern of Hsp70 expression, thyroid capsular invasion, Ki-67 expression index >7

A large-scale search for the genetic variants with a bias in the representation of alleles in transcriptome data (AE SNPs) and the binding sites in microRNA 3’-UTRs was performed and their functional significance was assessed using massively parallel reporter assay (MPRA). Of the 629,559 associated “SNP—gene” pairs (eQTLs) discovered in the human liver tissue according to the GTEx Analysis V8 data, 4394 polymorphic positions in the 3’-UTRs of the genes, which represent the eQTLs for these genes were selected. The TargetScanHuman 7.0 algorithm and PolymiRTS database were searched for the potential microRNA-binding sites. Of the predicted microRNA sites affected by eQTL-SNPs, we selected 51 sites with the best evidence of functionality according to Ago2-CLIP-seq, CLEAR-CLIP, and eCLIP-seq for RNA-binding proteins. For MPRA, a library of the plasmids carrying the main and alternative alleles for each AE SNP (in total, 102 constructs) was created. Allele-specific expression for 6 SNPs was detected by transfection of the HepG2 cell line with the constructed plasmid library and sequencing of target DNA and RNA sequences using the Illumina (MiSeq) platform.

This review contains literature data covering the structure and functions of the subfornical organ (SFO). The SFO belongs to the sensory group of formations located around the III and IV ventricles and constituting the circumventricular system of the brain. Despite its small size, the SFO has four departments, which differ from each other in the features of cyto-, myelo-, and angioarchitectonics. The structural features of the blood-brain barrier in the SFO allow many substances to directly contact with its cellular elements. A distinctive feature of the SFO is that circulating substances can stay in the capillaries for an unusually long time. Perivascular spaces, located around type I and III capillaries, penetrate the organ like thin channels and provide the substances in the interstitial fluid with a large surface area for interacting with the receptor field. A characteristic feature of the SFO is tanycytes, whose intertwining processes extend throughout the organ and form multiple contacts with neurons and the vascular bed. SFO is an important link in the regulation of homeostasis. It takes part in the regulation of blood pressure and drinking behavior, controls the water and electrolyte balance and energy metabolism, and also acts as an important link in neuro-immune interactions. Such structural and functional features of the SFO make it a promising object of neurobiological research.

Рязанский государственный медицинский университет имени

The correlation of histological features of papillary thyroid cancer with clinical and morphological prognostic factors and cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center (25 cases with lethal outcome and 64 follow-up controls). Significant variability was revealed in the histological structure of papillary thyroid cancer with the prevalence of classic (62%) and less frequent follicular (19%), tall cell (8%), and solid (7%) variants. In comparison with the classic variant, the solid variant was more often associated with male sex and large tumor size; follicular and tall cell variant was associated with more frequent metastases to regional lymph nodes; follicular and solid variants were associated with an increased proportion of cases with disease stages III-IV. The main differences reflecting the effect of histological factor on the disease outcome were associated with the solid variant of papillary thyroid cancer that was detected in 21% of lethal cases and only in 2% of control subjects. The detection of this variant can be of importance as an additional prognostic factor of the postoperative survival in papillary thyroid cancer.

The state of rat kidneys after injection of bone marrow multipotent stromal cells (MSC) labeled with Vybrant CM-Dil into intact or resected liver was studied by fluorescence microscopy. The main structural changes in the kidneys after MSC injection into intact and partially resected liver manifested as granular dystrophy and necrobiotic/necrotic changes in single epithelial cells of the distal tubules and collecting ducts, thrombosis of some vessels, progression of an ascending urinary tract infection (detection of dust-like fluorescent objects), which can be due to the immunomodulating or even immunosuppressive influence of MSC and their detritus. MSC injected into the intact or resected liver, as well as the products of their degradation were not detected in the kidneys at all terms of observation. After injection of MSC into partially resected liver, manifestations of bacterial contamination of the renal medulla appeared later. The injection of MSC into the liver can be complicated by thrombosis of the renal vessels, which should be taken into account when using this administration route in the cell therapy.

ДИНАМИКА ПЛОИДОМЕТРИЧЕСКИХ И МОРФОМЕТРИЧЕСКИХ ПОКАЗАТЕЛЕЙ ЯДЕР ГЕПАТОЦИТОВ ЧЕЛОВЕКА В ЗАВИСИМОСТИ ОТ ИНТЕНСИВНОСТИ ПЕРЕОХЛАЖДЕНИЯ

We studied ultrastructural reorganization of the myocardium in Wistar rats treated with doxorubicin (single intraperitoneal injection in a dose of 15 mg/kg) and atorvastatin (daily intragastric administration in a dose of 20 mg/kg for 7 days) individually and in combination. It was found that doxorubicin administered alone or in combination with atorvastatin induces disturbances of varying severity in cardiomyocyte ultrastructure indicating the development of regenerative and plastic myocardial insufficiency. In case of isolated administration of atorvastatin, lytic changes in myofibrils, increased autophagic processes, and segregation of the fibrillar and granular components in the nucleoli appeared in the ultrastructure of some cardiomyocytes with increasing the observation period. Ultrastructural stereological analysis revealed a tendency to a decrease in the volume density of myofibrils and mitochondria in all experimental groups in comparison with the control.

The possibility of dissemination of bone marrow multipotent stromal cells stained with Vybrant CM-Dil after injection into an intact and resected liver was studied using luminescence microscopy. Labeled cells were found in the kidneys, spleen, lungs, axillary, mesenteric, and inguinal lymph nodes. We observed dissemination of multipotent stromal cells and their detritus throughout the body that occurred only after filtration in the lungs, where most cells underwent destruction. Perivascularly located macrophages in various organs can phagocytize multipotent stromal cells and their detritus from blood vessels. The content of objects labeled with Vybrant CM-Dil in distant organs was significantly lower after multipotent stromal cell injection into the resected liver, which was associated with the deposition of cells in the damaged area of the organ and their partial entry into the abdominal cavity.

Quantitative and qualitative characteristics of cell infiltrates in male Wistar rats were studied from 14 days to 12 months after implantation of polypropylene and a biodegradable polymer obtained by electrospinning and consisting of 65% polycaprolactone and 35% polytrimethylene carbonate. It was found that a predominantly macrophage-giant cell reaction developed around the biodegradable polymer; it spread into the matrix and the number of cells in the infiltrate decreased, as the degradation progressed. Around polypropylene, mainly lymphocytic and leukocytic reaction was seen; it also decreased with time, but was characterized by a reverse increase in the number of lymphocytes. Immunohistochemical analysis showed that the proportion of CD38+ cells 12 months after implantation increased around polypropylene to a greater extent than around the biodegradable polymer, while the proportion of CD68+ cells decreased. These findings suggest that implantation of a biodegradable polymer caused no prolonged lymphocytic and plasma cell reaction in animals as in the case of polypropylene, which indicates that biodegradable polymer is a promising material for tissue engineering.

ФГБНУ «Институт молекулярной патологии и патоморфологии Федерального исследовательского центра фундаментальной и трансляционной медицины», Новосибирск Холодовая травма развивается вследствие действия на организм холода (низких температур).Патологическое действие низких температур может проявляться в виде общего переохлаждения организма, отморожений, а также их сочетания.Все более широкое внедрение и использование в современной медицине гипотермии как метода лечения в некоторых случаях приводит к развитию ятрогенных поражений холодом, при которых контролируемая гипотермия может перейти в неконтролируемую.Среди механизмов некробиотических изменений и причин гибели тканей в результате отморожений выделяют две концепции: теорию непосредственного повреждающего действия низких температур на ткани и теорию альтерации тканей при их отогревании.На современном этапе развития биомедицинских знаний гипотермия рассматривается как стресс, влияющий на орган и весь организм в целом.Одну из главных ролей в поддержании постоянства температуры тела играет эндокринная система

The purpose of this study was to study the structural and morphological reorganization of the rat myocardium during a single deep hypothermia in the experiment. The experiment was carried out on 20 male rats of the Wistar line. The duration of the experiment was 14 days. Hypothermia was modeled by immersing cells with experimental animals in containers with an average water temperature of + 5.0 °C. The average ambient (air) temperature was + 7.0°C. The immersion time of the animals averaged 40 minutes. When the rectal temperature reached ≤ 20°C, the animals were removed from the containers. Animals were taken out of the experiment on the 1st, 2nd, 7th and 14th days. Animals of the control group (5 individuals) were placed in water with a temperature of +30 degrees for the duration of the stay in the water of the rats of the experimental group. The preparations were stained with hematoxylin and eosin and by the GOFP method (according to Lie). Immediately after hypothermia (day 1), cardiomyocytes showed myolysis, loss of striation, and pycnosis of the nuclei. When stained for GOFP, extensive fields of fuchsinophilic myocardium were observed. On the second day of the experiment, the phenomena of myolysis, loss of striation and pycnosis of the nuclei of muscle cells persisted, but the phenomena of myocardial fuchsinophilia decreased. On the seventh day, the phenomena of myolysis and the number of fixinophilic cardiomyocytes continued to decrease, the nuclei looked enlarged. On the fourteenth day, the phenomena of myolysis disappeared, the nuclei decreased in size, fuchsinophilia was noted in single cardiomyocytes. Thus, hypothermia, as an unfavorable factor in the surrounding section, has a pronounced damaging effect on the cardiomyocytes of the cardiac muscle of experimental animals.

ФГБНУ «Институт молекулярной патологии и патоморфологии Федерального исследовательского центра фундаментальной и трансляционной медицины»

In order to optimize the testosterone model of benign prostatic hyperplasia, we studied the effect of castration and different doses of testosterone on the induction of the proliferative process in the prostate of Wistar rats. It was shown that 4-week subcutaneous administration of testosterone propionate in a dose of 20 mg/kg causes pronounced proliferative and hemodynamic disorders in the dorsolateral gland morphologically similar in castrated and non-castrated males. Administration of testosterone in a dose of 3 mg/kg had no significant effect on the dynamics of the pathological process in non-operated rats and normalized the structure of the gland in castrated animals. Morphological study showed that castration of males provides no visible advantages in reproducing the testosterone model of benign prostatic hyperplasia. The proposed non-traumatic modification of the model with a high dose of testosterone has good reproducibility and sensitivity to therapeutic agents, as shown by the example of finasteride.

We studied the effect of a new targeted drug Pefagtal that represents a conjugate in which the MS2 phage filled with a substance toxic to cells (thallium salts) is covalently linked to peptides containing the RGD motif. The antitumor and pronounced antimetastatic effects of Pefagtal were demonstrated on transplanted mouse tumors differing in histological type and status of metastasis: Krebs-2 ascites adenocarcinoma of the mammary gland, Lewis lung adenocarcinoma, hepatoma-29, and lung adenocarcinoma. It is assumed that the RGD motif mediates primary binding of the construct to αvβ3 and αvβ5 integrins that are predominantly overexpressed in the endothelial cells of tumor blood vessels and in tumor and metastatic cells.