Information Condition of Dog’s Liver at Pathologies

In the study the method of assessing adaptive and regenerative opportunities of the liver by assessing of its information state was applied. The research revealed achange in the nature of the information state of the tissue of the liver at hepatoadenoma, liver cancer and non-cancer pathologies. Discovered changes of the information parameters characterizing the liver, indicate various kinds of adaptive processes in the organ. It is shown that at the non-neoplastic diseases of the liver, tissue system uses the existing structural adaptation resources, but it tends tocollapse. Changes of the information parameters were more pronounced at malignant disease than at hepatoadenoma, it is revealed reduction of system reliability to negative value. When tumors of the liver, tissue system is simplified, ordered and directed the growth and increase the reliability, such system complicates the possibility of successful treatment of the organ in such pathologies.

Archiv Euromedica, 2020

Wistar rats in the reproductive period and the period of pronounced senile changes in norm and pathological conditions were studied. The same informational parameters were also determined for some non-oncological pathologies, for hepatocellular adenoma and for hepatocellular carcinoma at both ages. It is established that in ontogenesis there is an increase in the level of real structural diversity (Н) and coefficient of relative entropy of the system (h). At the same time a decrease of level of organization of system (S) and coefficient of relative organization of system (R) are noted. In the studied periods of ontogenesis, at similar pathologies and pathological processes in liver, in reproductive period of ontogenesis the organ is characterized by fewer deviations from the norm and higher level of adaptation and compensative abilities than in the period of pronounced senile changes. Changes in informational condition of liver at hepatitis have the same direction as ontogenetic changes. They lead to an increase in the disorder of the system and a decrease in the level of its integrity, which results in a decrease in the level of adaptive and compensatory resources. In tumors, a decrease in H and h was found with a simultaneous increase in S and R compared to age norms, which are more pronounced in malignant neoplasms. For all the studied pathologies, changes in the information state are more prominent in the liver of rats in the period of pronounced senile changes.

Conducted research shows that the resistance of organ to various influences depends on level of its organization. The tissue systems consisting of actively dividing cells on various stages of differentiation are more subject for various influences, than the organs consisting of highly specialized cells with low degree of proliferative activity. The conducted research shows that the studied organs can conditionally be divided into two groups depending on the value of an existing structural variety. The liver, kidneys, pancreas, stomach, mammary gland, skin, ovaries and endometriya entered the first group. These organs are characterized by H value bigger than 2 bits. All types of muscles and the lungs, which have made the second group, are characterized by the H value less than 2 bits. Level of the greatest possible information capacity and the information morphological organization in tissues of dogs is defined by extent of differentiation of tissue and level of its mitotic activity. Thus, quite essential level of information morphological organization and rather high levels of relative morphological entropy, information morphological redundancy are noted in the tissues consisting of highly specialized, low-active or inactive in proliferative aspect cells. Such biosystems are rather steady against influences as in them sufficient level of reserves which can be involved in adaptation process remains.

We investigated the information state of the skin of dogs with benign and malignant tumors. It was revealed that in all studied types of tumors information system of the skin becomes simpler, and as a result, increases its reliability and ordering, and the system is aimed at growth. It was found that the changes of information parameters are more pronounced in malignant pathologies than in benign tumors.

PLoS ONE, 2014

The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte 'know' when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger.

Cancer research, 1961

To study qualitative and quantitative relations between proliferation of bile ductules and hepatic fibrogenesis, experimental hepatic fibrosis was produced in rats by subacute ethionine intoxication, bile duct ligation, administration of a-naphthylisothiocyanate, and by a high fat-low protein diet. Regression of fibrosis was produced in ethionine-intoxicated animals by treatment with methionine, and the lesion was modified by cortisone treatment and simultaneous methionine administration. Hepaticprotein, RNA, DNA, and hydroxyproline as a measure of collagen were correlated with the histologie changes in cell population determined by differential cell counts. After 7 weeks of ethionine administration, collagen and DNA content increased 4-5 times. The liver weight and protein almost doubled. In the same period the total number of ductular cells increased about 50-fold, and mesenchymal cells doubled. After substitu tion of methionine for ethionine after 7 weeks, the liver catabolized about 3 times the collagen content of the control liver, and the number of ductular cells decreased pre cipitously. The hydroxyproline/DNA ratio, i.e., the ratio of collagen to total cell number, remained constant in all stages of fibrogenesis induced by ethionine, modi fications of ethionine intoxication, a-naphthylisothiocyanate intoxication, bile duct ligation, and in control animals. During recovery from ethionine intoxication, DNA content decreased more rapidly than did hydroxyproline content. It is suggested that the increase in total hepatic protein during ethionine intoxication is a reflection of the proliferation of ductules rather than the formation of an abnormal protein. This cellular proliferation seems to act as a stimulus for fibrogenesis, the ductular cells apparently forming a framework around which fibers are laid down by mesenchymal cells. The disappearance of this framework results in the removal of collagen with mesenchymal cells possibly playing a role in the rapid fibroclasia.

Liver Transplantation, 2011

Liver resection and liver transplantation are the treatment modalities with the greatest potential for curing hepatocellular carcinoma (HCC). Tumor recurrence after resection for HCC is, however, a major problem, and an increased rate of recurrence after living donor transplantation versus cadaveric whole liver transplantation has been suggested. Factors involved in liver regeneration may stimulate the growth of occult tumors. The aim of this project was to test the hypothesis that a microscopic HCC tumor in the setting of partial hepatectomy would show enhanced growth and signs of increased invasiveness corresponding to the size of the liver resection. Hepatectomy was performed to various degrees in groups of Buffalo rats with the concomitant implantation of a fixed number of hepatoma cells in the remnant liver; a control group underwent only resection. After 21 days, the sizes and numbers of the tumors and the expression of alpha-fetoprotein (AFP), cyclin D1, calpain small subunit 1 (CAPNS1), CD34 (a microvessel density marker), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2) were evaluated and compared between the groups. The tumor volume and number increased significantly with the size of the partial hepatectomy (P < 0.05). The largest resections were also associated with increased hepatoma cell infiltration in the lungs and significant up-regulation of cyclin D1, AFP, CAPNS1, CD34, VEGF, and VEGFR2. The results suggest that liver regeneration after partial hepatectomy facilitates the growth and malignant transformation of microscopic HCC, and this could be significant for liver resection and partial liver transplantation strategies for HCC. Liver Transpl 17:866-874,

IIAS, 2016

In this paper we are thinking, in a free way, about possible applications of the Information-Thermodynamics point of view in biology. We can consider a principle loss of information (structure) within the process of generation of cells by their duplication (dividing). Within any duplication of a cell the predecessor its follower is generated and the distortion of the duplicated (copied) structure (information) of the parent cell in the follower arises. This loss is measurable by the quantity of (average) information amount. It is a loss of part of message being copied (transferred), it is a loss of information within this process of such an information transfer. (The whole structure of the cell is a message, also including 'a program' for its functionality in a texture.) This mechanism of aging by a 'tooth of time' can be described in a functional way by the 'carnotized' model of information transfer - direct Carnot Cycle viewed informationally. The growth of thermodynamic entropy in its environment is similar to the mentioned loss of the cell structure, measured, in biology, by the shortenning the length of the cell telomere. The telomere is, approximatelly, a box of chromozomes and its length codes the age of the cell, or, the number of the cell's predecessors in the normal situation. Within the pathological proliferation of cells the opposite situation arises. In this case the cells with a precise structure} (but, of an \textit{another type} in comparison with the normal structure of its own original and 'normal' type) are generated. But, this grow of structure in a certain locality in the whole organism is paid by a pumping off energy from an environment of this locality. This situation is describable again by our Information-Thermodynamic model, but by a reverse this time. The decreasing value of thermodynamic entropy or increasing value of information entropy is now evidenced locally with the higher growth of the thermodynamic entropy in the environment. This process is similar to the growth of the cell structure in the pathological case which growth is now measured by the lengthening of the cell telomeres.

PLOS Computational Biology, 2023

We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.

Revista española de enfermedades digestivas : organo oficial de la Sociedad Española de Patología Digestiva, 2014

Liver regeneration (LR) is one of the most amazing tissue injury response. Given its therapeutic significance has been deeply studied in the last decades.LR is an extraordinary complex process, strictly regulated, which accomplishes the characteristics of the most evolutionary biologic systems (robustness) and explains the difficulties of reshaping it with therapeutic goals.TH reproduces the physiological tissue damage response pattern, with a first phase of priming of the hepatocytes-cell-cycle transition G0-G1–, and a second phase of proliferation –cell-cycleS/M phases– which ends with the liver mass recovering. This process has been related with the tissue injury response regulators as: complement system, platelets, inflammatory cytokines(TNF-a, IL-1b, IL-6), growth factors (HGF, EGF, VGF) and anti-inflammatory factors (IL-10, TGF-b).Given its complexity and strict regulation, illustrates the unique alternative to liver failure is liver transplantation.The recent induced pluripot...