Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have be... more Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. We identified 453 proteins across all study groups. Our results indicate that key event...
There is considerable concern about the substances present in the environment and their potential... more There is considerable concern about the substances present in the environment and their potential to interfere with the endocrine system of vertebrates. Among these, the so-called endocrine-disrupting compounds, which can modulate or disrupt developmental and reproductive processes, substances with estrogenic activity have attracted most attention. Concerns about the presence of these compounds in the environment have led to the development of screening and testing assays that are able to detect such substances and evaluate their potential to induce adverse effects. In vitro systems such as mammalian and fish cell lines have become of growing importance in toxicity testing of such compounds. The cytotoxic and apoptotic effects induced by 17α-ethynylestradiol and diethylstilbestrol were studied on CHO-K1 cell line. Trypan blue exclusion method was used to determine the cell viability. Cytotoxicity of 17α-ethynylestradiol (0.34–34 μM) and diethylstilbestrol (0.37–37 μM) was found to b...
Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogene... more Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored (interstitial fibrosis and tubular atrophy (IFTA) for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci > 1 and IFTA > 1) expressed ADAMTS-4 in INT more frequently in both groups (p = 0.005; p = 0.013; respectively). In paired c...
Extracellular matrix proteins are regulated by metzincin proteases, like the disintegrin metallop... more Extracellular matrix proteins are regulated by metzincin proteases, like the disintegrin metalloproteinases with thrombospondin motifs (ADAMTS) family members. This review focuses on the emerging role which ADAMTS-4 might play in vascular pathology, which has implications for atherosclerosis and vessel wall abnormalities, as well as for the resulting diseases, such as cardiovascular and cerebrovascular disease, aortic aneurysms, and dissections. Major substrates of ADAMTS-4 are proteoglycans expressed physiologically in smooth muscle cells of blood vessels. Good examples are versican and aggrecan, principal vessel wall proteoglycans that are targeted by ADAMTS-4, driving blood vessel atrophy, which is why this metzincin protease was implicated in the pathophysiology of vascular diseases with an atherosclerotic background. Despite emerging evidence, it is important not to exaggerate the role of ADAMTS-4 as it is likely only a small piece of the complex atherosclerosis puzzle and one ...
Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable cou... more Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progress...
AimTo assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrI... more AimTo assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrIII), a key regulator in TGFβ signaling, as a biomarker for diagnosis and stratification of patients with acute pancreatitis (AP).MethodsIn this small prospective pilot study, patients’ (N = 22) plasma samples were obtained at three time points: the first and fourth day of hospitalization and the day of hospital discharge. Healthy controls’ plasma (N = 25) was obtained at a single time point. Concentration of sTGFβrIII in plasma was determined by ELISA. Data were analyzed by fitting linear or linear mixed models.ResultsPlasma sTGFβrIII levels at presentation (day 1) were similar in AP patients and healthy participants, irrespectively of the disease severity. sTGFβrIII levels in patients were constant during hospital stay.ConclusionThese observations do not support further evaluation of plasma sTGFβrIII levels in this setting, but do not exclude a potential biological role of TGFβ and membrane-bound TGFβrIII in AP pathophysiology.
Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable cou... more Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progress...
Skripta sadrže opis, protokol i pripadne zadatke za sedam vježbi koje se izvode u okviru praktiku... more Skripta sadrže opis, protokol i pripadne zadatke za sedam vježbi koje se izvode u okviru praktikuma iz kolegija Bioloska kemija, studija Farmacije i studija Medicinske biokemije.
Galectins-1 and -3 modulate many cellular processes, and through regulation of cell migration, ph... more Galectins-1 and -3 modulate many cellular processes, and through regulation of cell migration, phagocytosis, immune cell degranulation and modulation of cytokine and inflammatory mediator production, these lectins are intimately involved in all phases of inflammatory reactions of innate and acquired immunity. Galectin-1 is generally considered a strong anti-inflammatory and galectin-3 a pro-inflammatory signal, but their effects tremendously vary with respect to their localization and the cell type. In this work we address the role of galectin-3 in the physiology of lymphocytes and the role and expression of galectins-1 and -3 in human monocytes and classically or alternatively differentiated and activated macrophages. Human lymphocytes and monocytes were isolated from the blood of healthy donors and differentiated into M1 and M2 subtype of macrophages by cultivation in culture media supplemented with granulocyte-macrophage or macrophage colony-stimulating factor, respectively. M1 m...
Revealing molecular signature in health and disease by modern mass spectrometry Jasna Peter Katal... more Revealing molecular signature in health and disease by modern mass spectrometry Jasna Peter Katalinić University of Rijeka, Department of Biotechnologyy and Croatian Proteomics Society Fundamental research in lifesciences on structure and function of biomolecules stays in a continuous support of modern medicine. The knowledge about molecular structure of complex biomolecules as key players in biological processes was shown to be invaluable for understanding of health and disease, whereas its analytical strategies are undergoing a transformation into an integrated „omics“ discipline. Experimental evidence previously collected by mass spectrometry during last decades is currently being put together with well established workflows using advanced new technology in mass spectrometers of ever increasing mass accuracy and speed of acquisition. In this introductory lecture of the symposium an overview on mass spectrometric strategies to reveal molecular signature in health and disease will ...
Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have be... more Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. We identified 453 proteins across all study groups. Our results indicate that key event...
There is considerable concern about the substances present in the environment and their potential... more There is considerable concern about the substances present in the environment and their potential to interfere with the endocrine system of vertebrates. Among these, the so-called endocrine-disrupting compounds, which can modulate or disrupt developmental and reproductive processes, substances with estrogenic activity have attracted most attention. Concerns about the presence of these compounds in the environment have led to the development of screening and testing assays that are able to detect such substances and evaluate their potential to induce adverse effects. In vitro systems such as mammalian and fish cell lines have become of growing importance in toxicity testing of such compounds. The cytotoxic and apoptotic effects induced by 17α-ethynylestradiol and diethylstilbestrol were studied on CHO-K1 cell line. Trypan blue exclusion method was used to determine the cell viability. Cytotoxicity of 17α-ethynylestradiol (0.34–34 μM) and diethylstilbestrol (0.37–37 μM) was found to b...
Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogene... more Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored (interstitial fibrosis and tubular atrophy (IFTA) for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci > 1 and IFTA > 1) expressed ADAMTS-4 in INT more frequently in both groups (p = 0.005; p = 0.013; respectively). In paired c...
Extracellular matrix proteins are regulated by metzincin proteases, like the disintegrin metallop... more Extracellular matrix proteins are regulated by metzincin proteases, like the disintegrin metalloproteinases with thrombospondin motifs (ADAMTS) family members. This review focuses on the emerging role which ADAMTS-4 might play in vascular pathology, which has implications for atherosclerosis and vessel wall abnormalities, as well as for the resulting diseases, such as cardiovascular and cerebrovascular disease, aortic aneurysms, and dissections. Major substrates of ADAMTS-4 are proteoglycans expressed physiologically in smooth muscle cells of blood vessels. Good examples are versican and aggrecan, principal vessel wall proteoglycans that are targeted by ADAMTS-4, driving blood vessel atrophy, which is why this metzincin protease was implicated in the pathophysiology of vascular diseases with an atherosclerotic background. Despite emerging evidence, it is important not to exaggerate the role of ADAMTS-4 as it is likely only a small piece of the complex atherosclerosis puzzle and one ...
Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable cou... more Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progress...
AimTo assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrI... more AimTo assess the potential of the soluble transforming growth factor β receptor type III (sTGFβrIII), a key regulator in TGFβ signaling, as a biomarker for diagnosis and stratification of patients with acute pancreatitis (AP).MethodsIn this small prospective pilot study, patients’ (N = 22) plasma samples were obtained at three time points: the first and fourth day of hospitalization and the day of hospital discharge. Healthy controls’ plasma (N = 25) was obtained at a single time point. Concentration of sTGFβrIII in plasma was determined by ELISA. Data were analyzed by fitting linear or linear mixed models.ResultsPlasma sTGFβrIII levels at presentation (day 1) were similar in AP patients and healthy participants, irrespectively of the disease severity. sTGFβrIII levels in patients were constant during hospital stay.ConclusionThese observations do not support further evaluation of plasma sTGFβrIII levels in this setting, but do not exclude a potential biological role of TGFβ and membrane-bound TGFβrIII in AP pathophysiology.
Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable cou... more Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progress...
Skripta sadrže opis, protokol i pripadne zadatke za sedam vježbi koje se izvode u okviru praktiku... more Skripta sadrže opis, protokol i pripadne zadatke za sedam vježbi koje se izvode u okviru praktikuma iz kolegija Bioloska kemija, studija Farmacije i studija Medicinske biokemije.
Galectins-1 and -3 modulate many cellular processes, and through regulation of cell migration, ph... more Galectins-1 and -3 modulate many cellular processes, and through regulation of cell migration, phagocytosis, immune cell degranulation and modulation of cytokine and inflammatory mediator production, these lectins are intimately involved in all phases of inflammatory reactions of innate and acquired immunity. Galectin-1 is generally considered a strong anti-inflammatory and galectin-3 a pro-inflammatory signal, but their effects tremendously vary with respect to their localization and the cell type. In this work we address the role of galectin-3 in the physiology of lymphocytes and the role and expression of galectins-1 and -3 in human monocytes and classically or alternatively differentiated and activated macrophages. Human lymphocytes and monocytes were isolated from the blood of healthy donors and differentiated into M1 and M2 subtype of macrophages by cultivation in culture media supplemented with granulocyte-macrophage or macrophage colony-stimulating factor, respectively. M1 m...
Revealing molecular signature in health and disease by modern mass spectrometry Jasna Peter Katal... more Revealing molecular signature in health and disease by modern mass spectrometry Jasna Peter Katalinić University of Rijeka, Department of Biotechnologyy and Croatian Proteomics Society Fundamental research in lifesciences on structure and function of biomolecules stays in a continuous support of modern medicine. The knowledge about molecular structure of complex biomolecules as key players in biological processes was shown to be invaluable for understanding of health and disease, whereas its analytical strategies are undergoing a transformation into an integrated „omics“ discipline. Experimental evidence previously collected by mass spectrometry during last decades is currently being put together with well established workflows using advanced new technology in mass spectrometers of ever increasing mass accuracy and speed of acquisition. In this introductory lecture of the symposium an overview on mass spectrometric strategies to reveal molecular signature in health and disease will ...
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