Pathophysiological and clinical point of view on Kawasaki disease and MIS-C.

This article compares two important pathophysiological states, Kawasaki disease, and multisystem inflammatory syndrome, in children associated with COVID-19 (MIS-C). Both occur predominantly in children, have a temporal association with an infectious agent, and are associated with immune-system alteration and systemic inflammation under certain circumstances. The two share common pathophysiology, including enhancement of interleukin-1 neutrophils, activation of the inflammasome, pyroptosis, or NETosis. Moreover, the clinical presentation of the diseases overlaps. However, they are indeed two separate diseases, proven by the differences in the epidemiological and etiological aspects and the pathophysiological processes involved in the development and frequency of some clinical signs. This article highlights potentially exciting areas that have not yet been studied in detail, which could help better understand the development of these diseases.

MUC13-miRNA-4647 axis in colorectal cancer: Prospects to identifications of risk factors and clinical outcomes.

MUC13, a transmembrane mucin glycoprotein, is overexpressed in colorectal cancer (CRC), however, its regulation and functions are not fully understood. It has been shown that MUC13 protects colonic epithelial cells from apoptosis. Therefore, studying MUC13 and MUC13-regulated pathways may reveal promising therapeutic approaches for CRC treatment. Growing evidence suggests that microRNAs (miRs) are involved in the development and progression of CRC. In the present study, the MUC13-miR-4647 axis was addressed in association with survival of patients. miR-4647 is predicted in silico to bind to the MUC13 gene and was analyzed by RT-qPCR in 187 tumors and their adjacent non-malignant mucosa of patients with CRC. The impact of previously mentioned genes on survival and migration abilities of cancer cells was validated in vitro. Significantly upregulated MUC13 (P=0.02) in was observed tumor tissues compared with non-malignant adjacent mucosa, while miR-4647 (P=0.05) showed an opposite trend. Higher expression levels of MUC13 (log-rank P=0.05) were associated with worse patient's survival. The ectopic overexpression of studied miR resulted in decreased migratory abilities and worse survival of cells. Attenuated MUC13 expression levels confirmed the suppression of colony forming of CRC cells. In summary, the present data suggested the essential role of MUC13-miR-4647 in patients' survival, and this axis may serve as a novel therapeutic target. It is anticipated MUC13 may hold significant potential in the screening, diagnosis and treatment of CRC.

Expression of classical mediators in hearts of rats with hepatic dysfunction.

Liver cirrhosis is associated with impairment of cardiovascular function including alterations of the heart innervation, humoral and nervous dysregulation, changes in systemic circulation and electrophysiological abnormalities. Choline acetyltransferase (ChAT), enzyme forming acetylcholine, tyrosine hydroxylase (TH), and dopamine-ß-hydroxylase (DBH), enzymes participating in noradrenaline synthesis, are responsible for the production of classical neurotransmitters, and atrial natriuretic peptide (ANP) is produced by cardiomyocytes. The aim of this study was to evaluate the influence of experimentally induced hepatic dysfunction on the expression of proANP, ChAT, TH, and DBH in the heart. Hepatic dysfunction was induced by application of thioacetamide (TAA) or by ligation of bile duct. Biochemical parameters of hepatic injury and levels of peroxidation in the liver and heart were measured. Liver enzymes measured in the plasma were significantly elevated. Cardiac level of peroxidation was increased in operated but not TAA group animals. In the left atrium of operated rats, the expression of TH and DBH was lower, while expression of ChAT remained unchanged. In TAA group, no significant differences in the expression of the genes compared to controls were observed. Liver injury induced by ligation leads to an imbalance in the intracardiac innervation, which might impair nervous control of the heart.

Asymptomatic abdominal aortic aneurysms show histological signs of progression: a quantitative histochemical analysis.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a serious disease due to its covert nature, relatively high prevalence and fatal prognosis in the case of rupture. To obtain new insights into AAA pathogenesis, we examined the relationships between histopathology, multiplex in vitro immunoassay data, diameter and symptomatology. METHODS: In a prospective, non-randomised study, we evaluated samples from 6 normal infrarenal aortae and 65 AAA patients (65 walls, 55 thrombi). The AAA patients were either asymptomatic (n = 44), symptomatic (n = 7) or with ruptured AAA (n = 14). The AAA diameter was classified as small (<5 cm, n = 18), medium (5-7 cm, n = 26) and large (>7 cm, n = 21). We quantified the histopathology of the AAA wall and the adjacent thrombus. We assessed the expression of proteins in the same samples. RESULTS: Asymptomatic AAAs had walls with more abundant inflammatory infiltrates, lower amounts of PAI-1, a higher number of tPA-positive elements, a tendency towards decreased collagen content, whereas the adjacent thrombi had a greater concentration of VCAM-1 and MMP-2 when compared with symptomatic AAAs. Compared with the aneurysmatic aorta, the normal aorta contained less collagen and more elastin, actin, desmin and PAI-1-positive elements; in addition, it was more vascular. Medium-sized AAAs were the most actin and vimentin rich, and large AAAs were the most vascular. CONCLUSION: Our results show that asymptomatic AAA walls often have more potentially deleterious histopathological alterations than symptomatic AAA walls. This result indicates that a progression from an asymptomatic AAA to rupture can be expected and screening patients who are at risk of rupture could be beneficial.

[Morphology and etiopathogenesis of the abdominal aortic aneurysm]. / Morfologie a etiopatogeneze aneuryzmatu brisní aorty.

The paper summarizes the latest research on the abdominal aorta aneurysm etiopathogenesis and compares normal aorta morphology with changes in the aortic aneurysm wall. The role of risk factors, especially hemodynamic and genetic, is discussed in detail. Special attention is paid to inflammatory processes including cytokines and matrix degrading proteases that contribute to the development of aneurysm. The role of thrombus and the current results of research into biomarkers indicating the risks and progression of the disease are analysed. Finally, a review of pharmacomodulation of the aortic aneurysm using statins, antibiotics, antihypertensive and nonsteroidal antiinflammatory drugs is presented.

Optimization of the model of abdominal aortic aneurysm--experiment in an animal model.

BACKGROUND: Many studies have been performed in order to model abdominal aortic aneurysm (AAA) in an experimental animal, most commonly in small laboratory animals. In our study, we tried to find the best AAA model in a pig by using various mechanical and enzymatic mechanisms. METHODS: Twenty-two pigs were operated on. We combined 3 mechanisms of creating an AAA, using an intraluminal infusion of porcine pancreatic elastase into the abdominal aortic segment, application of plastic cuff below the renal arteries causing turbulent blood flow, and inserting a patch into the longitudinal aortotomy. RESULTS: We found different results in different groups according to the mechanisms used. In group A, with a combination of the intraluminal elastase infusion and application of a stenosing cuff, AAA developed in all 7 animals (100%). In this group, we also found the largest histological changes in the abdominal aorta samples. CONCLUSION: The use of intraluminal pancreatic elastase infusion, together with increased turbulent flow caused by the stenosing cuff, seems to be the best model of AAA in pigs. This model is suitable for further research in the etiopathology of AAA. In fact, it is the first successful approach to a large-caliber native aneurysm model.