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  1. Article ; Online: Neutrophil Extracellular Traps in Fatal COVID-19-Associated Lung Injury

    Astrid Obermayer / Lisa-Maria Jakob / Jasmin D. Haslbauer / Matthias S. Matter / Alexandar Tzankov / Walter Stoiber

    Disease Markers, Vol

    2021  Volume 2021

    Abstract: An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a ...

    Abstract An excess formation of neutrophil extracellular traps (NETs), previously shown to be strongly associated with cytokine storm and acute respiratory distress syndrome (ARDS) with prevalent endothelial dysfunction and thrombosis, has been postulated to be a central factor influencing the pathophysiology and clinical presentation of severe COVID-19. A growing number of serological and morphological evidence has added to this assumption, also in regard to potential treatment options. In this study, we used immunohistochemistry and histochemistry to trace NETs and their molecular markers in autopsy lung tissue from seven COVID-19 patients. Quantification of key immunomorphological features enabled comparison with non-COVID-19 diffuse alveolar damage. Our results strengthen and extend recent findings, confirming that NETs are abundantly present in seriously damaged COVID-19 lung tissue, especially in association with microthrombi of the alveolar capillaries. In addition, we provide evidence that low-density neutrophils (LDNs), which are especially prone to NETosis, contribute substantially to COVID-19-associated lung damage in general and vascular blockages in particular.
    Keywords Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages

    Charlotte K. Y. Ng / Eva Dazert / Tuyana Boldanova / Mairene Coto-Llerena / Sandro Nuciforo / Caner Ercan / Aleksei Suslov / Marie-Anne Meier / Thomas Bock / Alexander Schmidt / Sylvia Ketterer / Xueya Wang / Stefan Wieland / Matthias S. Matter / Marco Colombi / Salvatore Piscuoglio / Luigi M. Terracciano / Michael N. Hall / Markus H. Heim

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 18

    Abstract: Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in ... ...

    Abstract Proteogenomic analyses of hepatocellular carcinomas (HCC) have focused on early-stage, HBV-associated tumours and lacked information about the phosphoproteome. Here, the authors present a comprehensive HCC proteogenomics and phosphoproteomics study in patient samples from multiple etiologies and stages.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Genomic analysis of focal nodular hyperplasia with associated hepatocellular carcinoma unveils its malignant potential

    Caner Ercan / Mairene Coto-Llerena / John Gallon / Lana Fourie / Mattia Marinucci / Gabriel F. Hess / Jürg Vosbeck / Stephanie Taha-Mehlitz / Tuyana Boldanova / Marie-Anne Meier / Alexandar Tzankov / Matthias S. Matter / Martin H. K. Hoffmann / Luca Di Tommaso / Markus von Flüe / Charlotte K. Y. Ng / Markus H. Heim / Savas D. Soysal / Luigi M. Terracciano /
    Otto Kollmar / Salvatore Piscuoglio

    Communications Medicine, Vol 2, Iss 1, Pp 1-

    a case report

    2022  Volume 8

    Abstract: Plain language summary Focal nodular hyperplasia (FNH) is a lesion resulting from the abnormal growth of liver cells. It is typically considered a benign tumor that does not become malignant. In rare cases, FNH may occur alongside malignant ... ...

    Abstract Plain language summary Focal nodular hyperplasia (FNH) is a lesion resulting from the abnormal growth of liver cells. It is typically considered a benign tumor that does not become malignant. In rare cases, FNH may occur alongside malignant hepatocellular carcinoma (HCC). In these cases, it is not known whether the malignant HCC may derive from the benign FNH. In this study, we reported on the analysis of a 74-year-old female patient with co-occurring FNH and HCC. We found that the FNH and HCC lesions were in fact genetically related, suggesting that the FNH gave rise to the HCC lesions. Furthermore, we found multiple cell populations within the FHN lesion that may be precursors to the HCC lesions suggesting that, in rare cases, FNH may be capable of progressing to malignant HCC. These findings may help to refine the surveillance strategy for these lesions.
    Keywords Medicine ; R
    Subject code 616
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver

    Shefaa AlAsfoor / Theresa V. Rohm / Angela J. T. Bosch / Thomas Dervos / Diego Calabrese / Matthias S. Matter / Achim Weber / Claudia Cavelti-Weder

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: Abstract Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti- ... ...

    Abstract Abstract Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, and how this impacts on NAFLD. We analyzed the pro- and anti-inflammatory gene expression of murine macrophages and human monocytes in vitro in the presence or absence of imatinib. In a time-resolved study, we characterized metabolic disease manifestations such as hepatic steatosis, systemic and adipose tissue inflammation as well as lipid and glucose metabolism in obese mice at one and three months of imatinib treatment. Our results showed that imatinib lowered pro-inflammatory markers in murine macrophages and human monocytes in vitro. In obese mice, imatinib reduced TNFα-gene expression in peritoneal and liver macrophages and systemic lipid levels at one month. This was followed by decreased hepatic steatosis, systemic and adipose tissue inflammation and increased insulin sensitivity after three months. As the transcription factor sterol regulatory element-binding protein (SREBP) links lipid metabolism to the innate immune response, we assessed the gene expression of SREBPs and their target genes, which was indeed downregulated in the liver and partially in peritoneal macrophages. In conclusion, targeting both inflammatory and lipogenic pathways in macrophages and liver as shown by imatinib could represent an attractive novel therapeutic strategy for patients with NAFLD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration

    Manina M. Etter / Tomás A. Martins / Laila Kulsvehagen / Elisabeth Pössnecker / Wandrille Duchemin / Sabrina Hogan / Gretel Sanabria-Diaz / Jannis Müller / Alessio Chiappini / Jonathan Rychen / Noëmi Eberhard / Raphael Guzman / Luigi Mariani / Lester Melie-Garcia / Emanuela Keller / Ilijas Jelcic / Hans Pargger / Martin Siegemund / Jens Kuhle /
    Johanna Oechtering / Caroline Eich / Alexandar Tzankov / Matthias S. Matter / Sarp Uzun / Özgür Yaldizli / Johanna M. Lieb / Marios-Nikos Psychogios / Karoline Leuzinger / Hans H. Hirsch / Cristina Granziera / Anne-Katrin Pröbstel / Gregor Hutter

    Nature Communications, Vol 13, Iss 1, Pp 1-

    a prospective cross-sectional study

    2022  Volume 21

    Abstract: Both acute and chronic COVID-19 disease (also known as long-COVID) may affect the central nervous system. Here authors characterize the immunological profile of peripheral blood and cerebrospinal fluid of COVID-19 patients in order to identify the main ... ...

    Abstract Both acute and chronic COVID-19 disease (also known as long-COVID) may affect the central nervous system. Here authors characterize the immunological profile of peripheral blood and cerebrospinal fluid of COVID-19 patients in order to identify the main factors that contribute to neurological impairment and the severity of neurological symptoms in Sars-CoV-2 infection.
    Keywords Science ; Q
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Vascular endothelial growth factor A amplification in colorectal cancer is associated with reduced M1 and M2 macrophages and diminished PD-1-expressing lymphocytes.

    Katharina Burmeister / Luca Quagliata / Mariacarla Andreozzi / Serenella Eppenberger-Castori / Matthias S Matter / Valeria Perrina / Rainer Grobholz / Wolfram Jochum / Daniel Horber / Peter Moosmann / Frank Lehmann / Dieter Köberle / Charlotte K Y Ng / Salvatore Piscuoglio / Luigi Tornillo / Luigi M Terracciano

    PLoS ONE, Vol 12, Iss 4, p e

    2017  Volume 0175563

    Abstract: VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes ...

    Abstract VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes and PD-L1 tumoral and stromal expression in colorectal cancers harboring VEGFA amplification or chromosome 6 polysomy. 38 CRCs of which 13 harbored VEGFA amplification, 6 with Chr6 polysomy and 19 with neutral VEGFA copy number were assessed by immunohistochemistry for CD68 (marker for M1/M2 macrophages), CD163 (M2 macrophages), programmed death 1(PD-1)- tumor infiltrating and stromal lymphocytes as well as tumoral and stromal PD-1 ligand (PD-L1) expression. CRCs with VEGFA amplification or Chr6 polysomy were associated with decreased M1/M2 macrophages, reduced PD-1-expressing lymphocyte infiltration, as well as reduced stromal expression of PD-L1 at the tumor front. Compared to intermediate-grade CRCs, high-grade CRCs were associated with increased M1/M2 macrophages and increased tumoral expression of PD-L1. Our results suggest that VEGFA amplification or Chr6 polysomy is associated with an altered tumor immune microenvironment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Vascular endothelial growth factor A amplification in colorectal cancer is associated with reduced M1 and M2 macrophages and diminished PD-1-expressing lymphocytes.

    Katharina Burmeister / Luca Quagliata / Mariacarla Andreozzi / Serenella Eppenberger-Castori / Matthias S Matter / Valeria Perrina / Rainer Grobholz / Wolfram Jochum / Daniel Horber / Peter Moosmann / Frank Lehmann / Dieter Köberle / Charlotte K Y Ng / Salvatore Piscuoglio / Luigi Tornillo / Luigi M Terracciano

    PLoS ONE, Vol 12, Iss 4, p e

    2017  Volume 0175563

    Abstract: VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes ...

    Abstract VEGFA is an angiogenic factor secreted by tumors, in particular those with VEGFA amplification, as well as by macrophages and lymphocytes in the tumor microenvironment. Here we sought to define the presence of M1/M2 macrophages, PD-1-positive lymphocytes and PD-L1 tumoral and stromal expression in colorectal cancers harboring VEGFA amplification or chromosome 6 polysomy. 38 CRCs of which 13 harbored VEGFA amplification, 6 with Chr6 polysomy and 19 with neutral VEGFA copy number were assessed by immunohistochemistry for CD68 (marker for M1/M2 macrophages), CD163 (M2 macrophages), programmed death 1(PD-1)- tumor infiltrating and stromal lymphocytes as well as tumoral and stromal PD-1 ligand (PD-L1) expression. CRCs with VEGFA amplification or Chr6 polysomy were associated with decreased M1/M2 macrophages, reduced PD-1-expressing lymphocyte infiltration, as well as reduced stromal expression of PD-L1 at the tumor front. Compared to intermediate-grade CRCs, high-grade CRCs were associated with increased M1/M2 macrophages and increased tumoral expression of PD-L1. Our results suggest that VEGFA amplification or Chr6 polysomy is associated with an altered tumor immune microenvironment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

    Tsuguhisa Nakayama / Ivan T. Lee / Sizun Jiang / Matthias S. Matter / Carol H. Yan / Jonathan B. Overdevest / Chien-Ting Wu / Yury Goltsev / Liang-Chun Shih / Chun-Kang Liao / Bokai Zhu / Yunhao Bai / Peter Lidsky / Yinghong Xiao / David Zarabanda / Angela Yang / Meena Easwaran / Christian M. Schürch / Pauline Chu /
    Han Chen / Anna K. Stalder / David R. McIlwain / Nicole A. Borchard / Phillip A. Gall / Sachi S. Dholakia / Wei Le / Le Xu / Chih-Jaan Tai / Te-Huei Yeh / Elizabeth Erickson-Direnzo / Jason M. Duran / Kirsten D. Mertz / Peter H. Hwang / Jasmin D. Haslbauer / Peter K. Jackson / Thomas Menter / Raul Andino / Peter D. Canoll / Adam S. DeConde / Zara M. Patel / Alexandar Tzankov / Garry P. Nolan / Jayakar V. Nayak

    Cell Reports Medicine, Vol 2, Iss 10, Pp 100421- (2021)

    2021  

    Abstract: Summary: Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant ... ...

    Abstract Summary: Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.
    Keywords SARS-CoV-2 ; COVID-19 ; ACE2 ; TMPRSS2 ; ciliated epithelial cell ; IFN-β1 ; Medicine (General) ; R5-920
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

    Ivan T. Lee / Tsuguhisa Nakayama / Chien-Ting Wu / Yury Goltsev / Sizun Jiang / Phillip A. Gall / Chun-Kang Liao / Liang-Chun Shih / Christian M. Schürch / David R. McIlwain / Pauline Chu / Nicole A. Borchard / David Zarabanda / Sachi S. Dholakia / Angela Yang / Dayoung Kim / Han Chen / Tomoharu Kanie / Chia-Der Lin /
    Ming-Hsui Tsai / Katie M. Phillips / Raymond Kim / Jonathan B. Overdevest / Matthew A. Tyler / Carol H. Yan / Chih-Feng Lin / Yi-Tsen Lin / Da-Tian Bau / Gregory J. Tsay / Zara M. Patel / Yung-An Tsou / Alexandar Tzankov / Matthias S. Matter / Chih-Jaan Tai / Te-Huei Yeh / Peter H. Hwang / Garry P. Nolan / Jayakar V. Nayak / Peter K. Jackson

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile ... ...

    Abstract Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs

    Ivan T. Lee / Tsuguhisa Nakayama / Chien-Ting Wu / Yury Goltsev / Sizun Jiang / Phillip A. Gall / Chun-Kang Liao / Liang-Chun Shih / Christian M. Schürch / David R. McIlwain / Pauline Chu / Nicole A. Borchard / David Zarabanda / Sachi S. Dholakia / Angela Yang / Dayoung Kim / Han Chen / Tomoharu Kanie / Chia-Der Lin /
    Ming-Hsui Tsai / Katie M. Phillips / Raymond Kim / Jonathan B. Overdevest / Matthew A. Tyler / Carol H. Yan / Chih-Feng Lin / Yi-Tsen Lin / Da-Tian Bau / Gregory J. Tsay / Zara M. Patel / Yung-An Tsou / Alexandar Tzankov / Matthias S. Matter / Chih-Jaan Tai / Te-Huei Yeh / Peter H. Hwang / Garry P. Nolan / Jayakar V. Nayak / Peter K. Jackson

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile ... ...

    Abstract Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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