One of the factors contributing to colorectal cancer (CRC) development is inflammation, which is mostly hypoxia-associated. This study aimed to characterize the morphological and molecular biological features of colon tumors in mice that were tolerant and susceptible to hypoxia based on colitis-associated CRC (CAC). Hypoxia tolerance was assessed through a gasping time evaluation in a decompression chamber. One month later, the animals were experimentally modeled for colitis-associated CRC by intraperitoneal azoxymethane administration and three dextran sulfate sodium consumption cycles. The incidence of tumor development in the distal colon in the susceptible to hypoxia mice was two times higher and all tumors (100%) were represented by adenocarcinomas, while in the tolerant mice, only 14% were adenocarcinomas and 86% were glandular intraepithelial neoplasia. The tumor area assessed on serially stepped sections was statistically significantly higher in the susceptible animals. The number of macrophages, CD3−CD19+, CD3+CD4+, and NK cells in tumors did not differ between animals; however, the number of CD3+CD8+ and vimentin+ cells was higher in the susceptible mice. Changes in the expression of genes regulating the response to hypoxia, inflammation, cell cycle, apoptosis, and epithelial barrier functioning in tumors and the peritumoral area depended on the initial mouse’s hypoxia tolerance, which should be taken into account for new CAC diagnostics and treatment approaches development.
Environmental pollution with microplastics (MPs) can have a negative impact on human health. Certain findings point to the relationship between MP and the development of inflammatory bowel diseases (IBD). We investigated the effect of MP consumption on the severity of chronic colitis in male C57BL/6 mice. The MP effect was modeled by drinking water consumption with a suspension of 5 μm PS particles at a concentration of 10 mg/L replacement for 12 weeks. Chronic colitis was induced by three seven-day cycles of 1% DSS consumption (starting from the 8th, 29th and 50th days of the experiment). We investigated inflammatory infiltration, the goblet cell volume fraction and the highly sulfated and neutral mucins content in them, the endocrine cell number, the ulcerative-inflammatory process prevalence, changes in the gene’s expression encoding tight junction proteins, glycocalyx components proapoptotic factor Bax and proliferation marker Mki67 in the colon, and TNFα, IL-1β, IL-6 and IL-10 cytokines content in the serum. In healthy mice, MP did not cause pathological changes in the colon; however, indirect data indicate an increase in colon permeability. In chronic colitis, MP leads to higher prevalence of all pathological changes in general, and ulcers in particular, in a greater number of crypt abscesses and enteroendocrine cells. MP consumption leads to a more severe chronic colitis course.
Recently, evidence indicating that microplastics (MPs) have a hazardous effect on human health is accumulating. The potential of MPs having a role in carcinogenesis was suggested. Therefore, the aim of this study was to evaluate MPs’ effect on colitis-associated colorectal cancer (CAC) development. The AOM/DSS-induced CAC model was reproduced in two groups of adult male C56BL/6 mice. One of these groups received MPs (5 μm polystyrene microbeads) with drinking water at a dose of 1.48 mg/kg/day throughout the experiment (12 weeks), and the other received water untreated with MPs. In the colons of mice that consumed MPs, there was a higher number of tumor nodules at the macroscopic level, a greater tumor prevalence on histological sections, more pronounced inflammatory infiltration, a higher goblet cell volume fraction, the content of highly sulfated mucins was found in them, and there were more tumors with increased enteroendocrine cell content. We did not find any MP effects on the claudins, mucins, proapoptotic factor Bax, or on the proliferation marker Mki67 gene expression in the medial colon, nor on the serum level of TNFα, IL-1β, IL-6, and IL-10 cytokines. Thus, MPs promote the CAC development in mice by exacerbating intestinal local inflammation and damaging the epithelial barrier, and MPs may represent a potential environmental cofactor contributing to CAC risk.
Thrombotherapy is an important approach in treatment of various diseases associated with pathologies of the cardiovascular and human hemostasis systems. Screening for producers of modern, specific, and safe thrombolytic substances is an important task for medicine and biotechnology. The aim of this study was to characterize thrombolytic potential of seven strains of micromycete belonging to the genus Tolypocladium, which was obtained from White Sea soils. The Tolypocladium inflatum 62a strain was considered the most promising producer of thrombolytic agent activities suitable for possible use in thrombotherapy or diagnostics of hemostasis pathologies. It demonstrated a high radial growth rate and was characterized not only by a sufficiently high value of enzymatic index in media with fibrin and fibrinogen but also by the highest specificity for fibrillar proteins among all strains. The preparation obtained from it demonstrated pronounced thrombolytic effectiveness and substrate specificity.
Background/Objectives: The most commonly used method for determining tolerance to oxygen deficiency is applying a sublethal hypoxic load (SHL) in a decompression chamber at an altitude of 11,500 m. The aim of this study was to identify the morphofunctional characteristics of the immune system’s response to SHL in animals with different tolerances to oxygen deficiency. Methods: This study was conducted on male Wistar rats. Resistance to SHL was determined at a critical altitude (11,500 m) once in a decompression chamber. To study the features of the reaction to SHL, morphological and morphometric methods, flow cytometry, and real-time PCR were used. Results: One month after SHL, rats susceptible to hypoxia, in comparison with tolerant ones, demonstrated higher numbers of cytotoxic T-lymphocytes and NK cells in the peripheral blood, thymic bodies in the cyst-like cavities formed in the thymus, and wide germinal centers of lymphoid nodules in the spleen. At the same time, rats tolerant to hypoxia demonstrated higher numbers of B-lymphocytes in the peripheral blood and a narrow marginal zone of lymphoid nodules in the spleen. In addition, animals susceptible to hypoxia demonstrated higher expression levels of proinflammatory cytokines Il1b and Tnfa in peripheral blood leukocytes in comparison with tolerant animals. Conclusions: This indicates that the immune systems of tolerant and susceptible animals respond differently to oxygen deprivation during SHL, and that the manifestations of this effect persist for at least a month afterward. The obtained data should be taken into account when conducting experiments with reference to organisms’ initial hypoxia tolerance.
Existing diagnostic markers of sepsis indicate already developed inflammatory complications, whereas predictors enable preoperative identification of high-risk patients for preventive measures. This study aimed to evaluate the prognostic value of preoperative inflammatory biomarkers for postoperative complications in cardiac surgery patients. Preoperatively, we assessed age, body mass index, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), complete blood count with hematological indices including neutrophil-to-lymphocyte ratio (NLR), serum cytokines, HIF1A (hypoxia-inducible factor 1-alpha), and EPAS1 (endothelial PAS domain protein 1) expression in peripheral blood leukocytes. During surgery, cardiopulmonary bypass time, myocardial ischemia time, and blood loss were recorded. Postoperatively, complications, intensive care unit (ICU) stay, and total hospitalization were documented. No differences were found in non-modifiable risk factors or perioperative parameters between groups, except for longer ICU stay in the complications group. Preoperatively, absolute neutrophil count and NLR were higher in patients without complications, while eosinophil count, HIF1A expression, and HIF1A/EPAS1 ratio were higher in those with it. The HIF1A/EPAS1 ratio demonstrated the best diagnostic characteristics. Thus, preoperative predictors of postoperative inflammatory complications include low neutrophil count and NLR, as well as high HIF1A expression and HIF1A/EPAS1 ratio. These markers may facilitate early risk stratification and preventive strategies before surgery.