Biological rhythms of the liver.

The biological rhythm is a fundamental aspect of an organism, regulating many physiological processes. This study focuses on the analysis of the molecular basis of circadian rhythms and its impact on the functioning of the liver. The regulation of biological rhythms is carried out by the clock system, which consists of the central clock and peripheral clocks. The central clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and is regulated by signals received from the retinal pathway. The SCN regulates the circadian rhythm of the entire body through its indirect influence on the peripheral clocks. In turn, the peripheral clocks can maintain their own rhythm, independent of the SCN, by creating special feedback loops between transcriptional and translational factors. The main protein families involved in these processes are CLOCK, BMAL, PER and CRY. Disorders in the expression of these factors have a significant impact on the functioning of the liver. In such cases lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification can be significantly affected. Clock dysfunctions contribute to the pathogenesis of various disorders, including fatty liver disease, liver cirrhosis and different types of cancer. Therefore understanding circadian rhythm can have significant implications for the therapy of many liver diseases, as well as the development of new preventive and treatment strategies.

The Association of Serum Profile of Transferrin Isoforms with COVID-19 Disease Severity.

Background/Objective: Bearing in mind the relationship of transferrin (TRF) microheterogeneity with the biological activity of its isoforms, we propose, in this study, to determine the association of the profile of TRF isoforms with COVID-19 disease severity and to compare this profile to the profiles of other diseases. Methods: The disease group consisted of 96 patients from whom blood was collected twice, upon admission to the ward and after treatment (on average on the ninth day). TRF isoforms were separated by capillary electrophoresis. The analysis included disease severity, cytokine storm, comorbidities, patient survival, oxygen therapy, and modified early warning scores (MEWSs). Results: The concentration of 5-sialoTRF was higher in patients compared to controls at the beginning and during COVID-19 treatment. The concentration of this isoform varies with the severity of disease and was higher in critical patients than those with a moderate condition. Additionally, the level of 5-sialoTRF was lower and the level of 4-sialoTRF was higher in patients with comorbidities than that in patients without them. The concentration of 5-sialoTRF was lower and the concentration of 4-sialoTRF was higher in surviving patients than in non-surviving patients. There were no statistical changes in TRF isoforms according to presence of cytokine storm, MEWS, and oxygen therapy. Conclusions: We conclude that the profile of TRF isoforms in COVID-19 patients differs from that in other diseases. An increase in the concentration of a sialic acid-rich isoform, 5-sialoTRF, may be a compensatory mechanism, the goal of which is to increase oxygen delivery to tissues and is dependent on the severity of the disease. Additionally, the concentration of 5-sialoTRF may be a prognostic marker of the survival of COVID-19 patients.

The Diagnostic Value of FibroTest and Hepascore as Non-Invasive Markers of Liver Fibrosis in Primary Sclerosing Cholangitis (PSC).

The aim of this study was to evaluate the diagnostic usefulness of two non-invasive, validated, and patented markers of liver fibrosis, the Hepascore and FibroTest, in patients with primary sclerosing cholangitis (PSC). The study group consisted of 74 PSC patients and 38 healthy subjects. All patients had a liver biopsy. The Hepascore and FibroTest were calculated using specific algorithms. The ANOVA rank Kruskal-Wallis test revealed differences in the Hepascore and FibroTest between patients divided according to histological stage (p < 0.001 for both comparisons). The Hepascore and FibroTest had significantly higher results in patients with significant fibrosis (F ≥ 2) in comparison to those with no significant fibrosis (F1) (p < 0.001 for both tests) and higher values in patients with cirrhosis (F4) when compared to those without cirrhosis (F1-F3) (p < 0.001 for both comparisons). The Hepascore test showed a diagnostic sensitivity of 96.8%, a specificity of 100% for fibrosis (at cut-off 0.52) and a diagnostic sensitivity of 95.2%, and a specificity also of 100% for cirrhosis (at 0.80). The FibroTest in point 0.51 for the diagnosis of fibrosis obtained the following values: 58.6%, 90%, 89.5%, and 60%, respectively, and in point 0.73 for the diagnosis of cirrhosis: 42.9%, 100%, 100%, and 45.5, respectively. The Hepascore test reached an excellent diagnostic power in identifying both fibrosis and cirrhosis (AUC = 1.0). The FibroTest and Hepascore are highly valuable for the evaluation of the severity of liver fibrosis and cirrhosis in PSC patients and can be used as a primary screening method, allowing for a significant reduction in the need for liver biopsy. Both markers have the required sensitivity and specificity to detect liver fibrosis and cirrhosis and can be equally used in clinical practice, although the Hepascore seems to be a better test because it is more specific.