Browsing by Author "Vucevic, Danijela (55881342600)"

Periportal hepatocytes (PPHs) and perivenous hepatocytes (PVHs) in standard optical microscopy appear to be morphologically identical. However, the functional properties of these two cell populations and their roles in liver lobules are not the same. Despite significant differences in gene expression between these two hepatocyte populations, it is still unclear whether the differences are present at the higher levels of chromatin organization. In this study, we present results, indicating that periportal and perivenous hepatocytes, when stained using toluidine blue histological dye, have different chromatin textural patterns quantified with gray-level co-occurrence matrix (GLCM) method. Hepatic tissue was obtained from ten male, healthy mice. Chromatin structures were analyzed using GLCM. For each structure, we measured the values of angular second moment, inverse difference moment, GLCM Contrast, GLCM Variance, and GLCM Sum Variance. The results indicate that there is a statistically significant difference in all GLCM mathematical parameters except the contrast. In addition, some chromatin GLCM features were in correlation with serum aminotransferase levels in perivenous, but not in periportal hepatocytes. To the best of our knowledge, this is the first study to test the nuclear morphological differences between hepatocytes using GLCM and to investigate the respective relation with serum liver enzymes. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Periportal hepatocytes (PPHs) and perivenous hepatocytes (PVHs) in standard optical microscopy appear to be morphologically identical. However, the functional properties of these two cell populations and their roles in liver lobules are not the same. Despite significant differences in gene expression between these two hepatocyte populations, it is still unclear whether the differences are present at the higher levels of chromatin organization. In this study, we present results, indicating that periportal and perivenous hepatocytes, when stained using toluidine blue histological dye, have different chromatin textural patterns quantified with gray-level co-occurrence matrix (GLCM) method. Hepatic tissue was obtained from ten male, healthy mice. Chromatin structures were analyzed using GLCM. For each structure, we measured the values of angular second moment, inverse difference moment, GLCM Contrast, GLCM Variance, and GLCM Sum Variance. The results indicate that there is a statistically significant difference in all GLCM mathematical parameters except the contrast. In addition, some chromatin GLCM features were in correlation with serum aminotransferase levels in perivenous, but not in periportal hepatocytes. To the best of our knowledge, this is the first study to test the nuclear morphological differences between hepatocytes using GLCM and to investigate the respective relation with serum liver enzymes. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Uveitis is a group of inflammatory ocular diseases, primarily affecting uveal tract. Although the pathogenesis of endogenous uveitis is not completely understood, it is well established that immune mechanisms are involved. Cytokines are soluble proteins that function as mediators of immune responses and understanding their role in the development of endogenous uveitis could contribute to elucidation of the etiopathogenesis of this disease. In this review article the role of the most important cytokines is analyzed based on data from the studies with experimental animal models or patients with endogenous uveitis. Cytokines, such as interleukin-1, interleukin-2, interleukin-6 or tumor necrosis factor-alpha, have clear pro-inflammatory role in endogenous uveitis, while protective, anti-inflammatory role is ascribed to interleukin-10 and transforming growth factor-beta. Due to scarce and often contradictory results, the roles of interleukin-4, interleukin-5, interleukin-12, interleukin-17, interleukin-23, interferon-gamma and other cytokines in the pathogenesis of endogenous uveitis have not been unambiguously defined. Further studies are needed to delineate the precise role of these cytokines in endogenous veitis, which would open new possibilities in the treatment of this disease and prevention of its complications that can lead to vision loss.

Having in mind the influence of lipid profile in initiation and development of atherosclerosis, we examined the concentration of total cholesterol, triglycerides, low density lipoproteins and high density lipoproteins in the serum from rabbits with experimental atherosclerosis induced by a hypercholesterolemic diet (4% solution of crystalline cholesterol in edible oil). For this study three groups of rabbits were used: a control group fed on the standard diet for this species (n=7), control group fed on an oil-containing diet (n=7) and experimental group fed on a hypercholesterolemic diet (n=7). After two months of treatment we examined the serum concentration of lipids by using enzymatic colorimetric method. Experimental atherosclerosis was confirmed pathohistologically. The levels of concentration of total cholesterol and low density lipoproteins were highly significantly increased (p<0.01) in the sera of the investigated groups compared to the control group. In comparison with the control group the concentration of triglycerides was highly significantly decreased (p<0.01) in the serum of investigated groups. The level of high density lipoproteins was significantly decreased in the serum of the investigated groups compared to the control group, as well as in the serum of experimental group fed on a hypercholesterolemic diet compared to the control group fed on an oil-containing diet (p<0.05 respectively). Our findings indicate that lipid profile has an important role in the pathogenesis of experimental atherosclerosis.

Bronchial asthma is defined as a chronic inflammatory disease of the airways. Nowadays, it is believed that asthma is not a single entity, but a spectrum of diseases (syndrome rather than a disease), that have more or less common pathophysiologic outcomes. In all forms of asthma fibroblasts and other effector cells of the inflammatory response secrete a wide range of preformed and newly generated mediators, which damage the bronchial epithelium, contract smooth muscle and increase mucous secretion. Besides, fibroblasts are of great importance in development of subepithelial fibrosis, smooth muscle hypertrophy and new vessel formation, which lead to the remodelling of airway wall. They also stimulate and modulate inflammation by increasing synthesis of interleukin-8 and monocyte chemotactic proteins. There is ample evidence that oxidants generation is increased during an asthma exacerbation. Fibroblast-derived oxygen metabolites can directly damage a variety of extracellular membrane proteins and/or impair function of antiproteases and/or inactivate enzymes that are involved in elastin synthesis and pulmonary tissue regeneration. However, scientists are still far from the complete understanding of bronchial asthma pathogenesis. Since fibroblasts have been recognized as effector cells capable of inducing pathophysiological features of asthma, there is a hope that further investigations of their role in bronchial asthma pathogenesis will improve treatment of this disease.

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver. © 2024 by the authors.

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF−/− C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF−/−; MIF−/−+Bet; TAA group, which received TAA; TAA+Bet; MIF−/−+TAA; and MIF−/−+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver. © 2024 by the authors.