Papers by Miroslaw Kornek
Frontiers in Immunology, Nov 14, 2023
Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to sup... more Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma. Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging. Methods: To this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model. Results: We found that small EVs derived from monocytes CD14 + and CD14 + CD61 + were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9 + CD14 + and CD14 + CD61 + small EVs exhibited superior performance compared to CD9 + CD61 + small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and Frontiers in Immunology frontiersin.org 01
Journal of Hepatology, 2018
Frontiers in Immunology, Apr 20, 2015
In recent years, it has been an explosion of information regarding the role of various myeloid ce... more In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.
Frontiers in Immunology, Sep 1, 2014
Cell-derived vesicles in particular extracellular vesicles (EVs) such as microparticles (MPs) and... more Cell-derived vesicles in particular extracellular vesicles (EVs) such as microparticles (MPs) and microvesicles besides exosomes are raising more and more attention as a novel and unique approach to detect diseases. It has recently become apparent that disease specific MP signatures or profiles might be beneficial to differentiate chronic liver diseases such as non-alcoholic fatty liver disease and chronic hepatitis C, to monitor their progression or possibly to assess treatment outcome. Therefore EVs might serve as a novel inexpensive and minimally invasive method to screen risk patients for the outbreak of a disease even before the initial symptoms, to follow up treatment complications and disease relapse. The purpose of the current review is to summarize already published EVs signatures for a limited number of exemplary diseases and to discuss their possible impact. Additionally, it will be discussed if the combination of EV profiling and miRNA profiling could be a future joint tool for the purpose of detecting cancer and from far larger interest to ultimately distinguish among various tumor entities. EVs might increase the chance of early detection of chronic diseases or cancers especially if applied as part of yearly health screenings in the future.
Zeitschrift Fur Gastroenterologie, Jan 16, 2006
Zeitschrift Fur Gastroenterologie, Aug 1, 2007
Oncology Letters, Jun 23, 2021
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 Intern... more This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
Hepatology communications, Jan 2, 2019
Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by ce... more Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses. Alteration in the concentration and composition of EVs in biological fluids is a typical hallmark of pathologies in different liver diseases. Circulating EVs can serve as biomarkers or as messengers following uptake by other cells. This review is a meeting report from the International Liver Congress 2018 (European Association for the Study of the Liver) celebrated in Paris (Symposium: Extracellular vesicles and signal transmission) that discusses the role of EVs in several liver diseases, highlighting their potential value as disease biomarkers and therapeutic opportunities. (Hepatology Communications 2019;3:305-315). E xtracellular vesicles (EVs) are small cellderived structures enveloped by a double-layer membrane that are shed by cells as a mechanism of horizontal communication. First described as an outgrowth of platelet activity or sample contamination, the role of EVs remained largely unexplored (1,2) until the early 2000s when growing enthusiasm for the field of EV biology and pathobiology resulted in increasing numbers of new publications each year. The potential of EVs as diagnostic and prognostic tools is being increasingly recognized by the scientific community and awaits translation into human medicine. Currently, three major types of EVs are recognized: exosomes, microvesicles (MVs), and apoptotic bodies. Despite some disagreements over their exact
Liver International, May 1, 2019
The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non-invasive ... more The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non-invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/ biochemical features, imaging techniques and analysis of non-specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non-invasive biomarkers, by using innovative techniques and high-throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research.
Journal of Hepatology, 2017
Cells, Sep 17, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Hepatology, 2017
The CB1-involved M1 polarization was apparently impaired by PTX (G(α) i/o protein inhibitor), Y27... more The CB1-involved M1 polarization was apparently impaired by PTX (G(α) i/o protein inhibitor), Y27632 (ROCK inhibitor) and PD98059 (ERK inhibitor), while SB203580 (p38 inhibitor) and compound C (AMPK inhibitor) had no such effects. We found the mechanism of activated CB1 promoting M1 polarization of BMMs was depended on G(α) i/o /RhoA/NF-κB p65 signaling pathway and G(α) i/o /ERK1/2 signaling pathway, respectively. Conclusions: CB1 plays a crucial role in regulating M1 polarization of BMMs in liver fibrosis via RhoA/NF-κB p65 and ERK1/2 signaling pathways, respectively. FRI-059 Beneficial effects of octrotide on intrahepatic angiogenesis via somatostatin receptor 2 in portal hypertensive and cirrhotic rats
Journal of Hepatology, 2008
Background and Aims: VEGF is known as one of the most potent promotors of tumor angiogenesis and ... more Background and Aims: VEGF is known as one of the most potent promotors of tumor angiogenesis and growth. The direct inhibition of VEGF-expression via RNA interference, in connection with decreased translation and secretion of VEGF is of special interest in the treatment of Hepatocellular Carcinoma (HCC). Here, we analysed the effects of direct VEGF inhibition via RNA interference on endothelial cells in vitro and in vivo. Methods: Functional effects of siRNA-VEGF were analysed in vitro using SVEC4−10 murine endothelial cells. For treatment of subcutanous and orthotopic HCC in mice, siRNA-CONT (control) or siRNA-VEGF were intraperitoneally injected every two days after tumor cell implantation. Apart from the tumor phenotype, effects of siRNA-VEGF on VEGF expression were analysed by semiquantitative PCR and ELISA technique. Inhibition of blood vessel formation was analysed by CD31 staining. Results: First, expression of VEGF and VEGF receptors was verified by RT-PCR, showing VEGF, VEGFR1 and Nrp1 expression in SVEC4−10. Transfection of SVEC4−10 with siRNA-VEGF reduced VEGF expression by 47% compared to the control. Proliferation was reduced by 23% in siRNA-VEGF treated SVEC4−10 compared to controls, whereas apoptosis was not influenced by siRNA-VEGF treatment. Tube formation was decreased by 38% compared to siRNA-CONT treated cells. Intraperitoneal treatment with siRNA-VEGF led to reduced subcutaneous (−34%) and orthotopic (−64%) tumor growth compared to controls. mRNA levels of VEGF, VEGF-receptors and neuropilin were decreased compared to the control. VEGF, VEGFR1, VEGFR2 and HIF1-alpha was also reduced after intraperitoneal treatment of subcutaneous liver tumors. CD31 staining showed reduced blood vessel formation (−66%) in siRNA-VEGF treated animals compared to siRNA-CONT treated animals. Conclusions: These data demonstrate that post-transcriptional inhibition of VEGF-expression leads to the inhibition of functional effects of endothelial cells in vitro and in vivo. Therefore, siRNA-VEGF might be a potent therapeutic tool in future treatment of HCC.
Zeitschrift Fur Gastroenterologie, 2007
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Journal of Hepatology, Apr 1, 2007
Mononuclear liver cells, harvested after lobectomy (left lobe) (n = 5) and collagenase-dissociati... more Mononuclear liver cells, harvested after lobectomy (left lobe) (n = 5) and collagenase-dissociation, were plated on a semi-solid medium designed for the assessment of colony-forming potential of hematopoietic progenitors. Liver cells were characterized using flow cytometry and cell populations were sorted in order to evaluate their hematopoietic potential in vitro. The expression of mRNAs coding for hematopoietic and endodermic markers was studied for each cell population to determine if these cells were of hepatic or hematopoietic origin. Finally, liver cells were co-cultured with mesenchymal stem cells in an attempt to amplify the colony-forming unit (CFU) number. We showed that a clonogenic potential [ie CFU-Granulocyte Erythrocyte Macrophage Megakaryocyte (CFU-GEMM), CFU-Granulocyte Monocyte (CFU-GM) and Burst Forming Unit Erythrocyte (BFUe)] could be observed within mononuclear liver cells plated in presence of Bone Morphogenic Protein-4. Two main cell populations were identified by flow cytometry: CD45+ cells with a lymphocyte-like morphology and CD34+/CD45-cells. Cell sorting experiments demonstrated that the clonogenic activity previously observed is restricted to the CD34+/CD45cell population. Further characterization experiments showed that: (i) this liver cell population expressed the CD90 and CD105 antigens but was negative for CD45, CDI 84 and CDI 17 antigens, (ii) the CD34+/CD45
Biology, Aug 4, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Methods in molecular biology, 2017
Larger extracellular vesicles, microparticles (MPs) or microvesicles (MVs), especially their acqu... more Larger extracellular vesicles, microparticles (MPs) or microvesicles (MVs), especially their acquisition and characterization by flow cytometry (FACS), is increasingly in focus of clinical/translational research efforts. Several laboratories have shown that MPs/MVs might be suitable for the diagnosis and predicting prognosis in various diseases including cancer. However, FACS staining of larger extracellular vesicles (EVs) can be difficult and results potentially in false positive and inconsistent data interpretation. Despite that FACS equipment is well maintained and the operators have ample experience, a reliable and for larger EVs optimized staining protocol is missing. Here, we aim to close that gap and provide a working multi-antibody staining protocol for larger EVs isolated from human serum samples. We describe in detail the needed steps as currently done in our laboratory. Staining is demonstrated exemplarily for multi-antibody mix including CD147 , a potential cancer marker if applied in combination with other MP/MV surface markers.
Frontiers in Immunology, Mar 28, 2018
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical loc... more The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses. How the various antigen-presenting cell (APC) populations contribute to this process and how they handle danger signals determine the outcome of the generated immune responses. Importantly, liver mounted responses convey consequences not only for the local but also to systemic immunity. Here, we discuss various aspects of antigen presentation and its consequences by the non-professional APCs in the liver microenvironment.
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Papers by Miroslaw Kornek