LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 55

Search options

  1. Article ; Online: Advances and transgressions of nuclear transport checkpoint inhibitors.

    Hawiger, Jacek

    Molecular therapy : the journal of the American Society of Gene Therapy

    2024  

    Language English
    Publishing date 2024-04-04
    Publishing country United States
    Document type Letter
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2024.03.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Heartfelt sepsis: microvascular injury due to genomic storm.

    Hawiger, Jacek

    Kardiologia polska

    2018  Volume 76, Issue 8, Page(s) 1203–1216

    Abstract: Sepsis is one of the ten leading causes of death in developed and developing countries. In the United States, sepsis mortality approaches that of acute myocardial infarction and exceeds deaths from stroke. Neonates and the elderly are the most vulner- ... ...

    Abstract Sepsis is one of the ten leading causes of death in developed and developing countries. In the United States, sepsis mortality approaches that of acute myocardial infarction and exceeds deaths from stroke. Neonates and the elderly are the most vulner-able patients, with these groups suffering from the highest sepsis mortality. In both groups, many survivors respectively display serious developmental disabilities and cognitive decline. The National Institute of Health/National Heart, Lung, and Blood Institute Panel redefined sepsis as a "severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure." Microvas-cular endothelial injury in sepsis due to microbial inflammation encompasses small blood vessels (< 100 μm in diameter). While the lungs remain the principal organ of interest due to sepsis-associated acute respiratory distress syndrome, "septic heart" or "septic cardiomyopathy" accelerates sepsis' transition to potentially lethal septic shock. This review analyses both new advances in understanding the septic mechanism and possible resolutions of sepsis. The concept of a "genomic storm," caused by microbes triggering florid production of inflammatory mediators, is based on septic reprogramming of the human genome. This genomic storm leads to microvascular endothelial injury, persistent hypotension, and organ failure. While very early control of sepsis-causing bacterial, fungal and viral infections remains crucial for the treatment of sepsis, supportive measures are likewise necessary to maintain blood pressure, respiration, and kidney function. New evidence indicates that preadmission b-blockers may reduce sepsis-associated mortality. The fundamental role of nuclear signalling in the progres-sion and resolution of sepsis was established with a new class of cell-penetrating nuclear transport modifiers (NTMs). NTMs target the translocation of proinflammatory and metabolic transcription factors to the cell's nucleus while also enhancing bacterial clearance in experimental polymicrobial sepsis models. The result is a 700-fold reduction in the bacterial burden of the lungs and improvement of sepsis-associated thrombocytopaenia and blood markers of endothelial injury. When added to anti-microbial therapy, NTM has increased survival from 30% to 55%, when compared to antimicrobial therapy alone. Yet, the prevention of sepsis remains the most rational and beneficial path. Anti-pneumococcal vaccination has reduced the incidence of pneumonia and sepsis caused by increasingly antibiotic-resistant Streptococcus pneumoniae in all age groups. Similarly, the incidence of meningococcal sepsis known as "purpura fulminans" has been reduced by a recently approved vaccine thereby preventing hearing loss, neurologic damage, and limb amputations in young survivors of septic outbreaks. We urgently need further preventive, diagnostic, and therapeutic measures as the tide of sepsis rises in the United States and around the world.
    MeSH term(s) Endothelium, Vascular ; Humans ; Microvessels ; Multiple Organ Failure ; Sepsis/microbiology ; Sepsis/physiopathology
    Language English
    Publishing date 2018-07-05
    Publishing country Poland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 411492-9
    ISSN 1897-4279 ; 0022-9032
    ISSN (online) 1897-4279
    ISSN 0022-9032
    DOI 10.5603/KP.a2018.0146
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.B 598: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 474: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Activation of thousands of genes in the lungs and kidneys by sepsis is countered by the selective nuclear blockade.

    Qiao, Huan / Zienkiewicz, Jozef / Liu, Yan / Hawiger, Jacek

    Frontiers in immunology

    2023  Volume 14, Page(s) 1221102

    Abstract: The steady rise of sepsis globally has reached almost 49 million cases in 2017, and 11 million sepsis-related deaths. The genomic response to sepsis comprising multi-system stage of raging microbial inflammation has been reported in the whole blood, ... ...

    Abstract The steady rise of sepsis globally has reached almost 49 million cases in 2017, and 11 million sepsis-related deaths. The genomic response to sepsis comprising multi-system stage of raging microbial inflammation has been reported in the whole blood, while effective treatment is lacking besides anti-microbial therapy and supportive measures. Here we show that, astoundingly, 6,237 significantly expressed genes in sepsis are increased or decreased in the lungs, the site of acute respiratory distress syndrome (ARDS). Moreover, 5,483 significantly expressed genes in sepsis are increased or decreased in the kidneys, the site of acute injury (AKI). This massive genomic response to polymicrobial sepsis is countered by the selective nuclear blockade with the cell-penetrating Nuclear Transport Checkpoint Inhibitor (NTCI). It controlled 3,735 sepsis-induced genes in the lungs and 1,951 sepsis-induced genes in the kidneys. The NTCI also reduced without antimicrobial therapy the bacterial dissemination: 18-fold in the blood, 11-fold in the lungs, and 9-fold in the spleen. This enhancement of bacterial clearance was not significant in the kidneys. Cumulatively, identification of the sepsis-responsive host's genes and their control by the selective nuclear blockade advances a better understanding of the multi-system mechanism of sepsis. Moreover, it spurs much-needed new diagnostic, therapeutic, and preventive approaches.
    MeSH term(s) Humans ; Sepsis/genetics ; Kidney ; Respiratory Distress Syndrome/genetics ; Genomics ; Lung
    Language English
    Publishing date 2023-08-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1221102
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Book: Platelets / B

    Hawiger, Jacek

    receptors, adhesion, secretion

    (Methods in enzymology ; 215)

    1992  

    Author's details ed. by Jacek Hawiger
    Series title Methods in enzymology ; 215
    Platelets
    Collection Platelets
    Language English
    Size XXVII, 526 S. : Ill., graph. Darst.
    Edition 1. [Dr.]
    Publisher Acad. Pr
    Publishing place San Diego u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT004354462
    ISBN 0-12-182116-1 ; 978-0-12-182116-6
    Database Catalogue ZB MED Medicine, Health

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Se 222 -215- verfügbar in Königswinter Königswinter

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Book: Platelets / B

    Hawiger, Jacek

    receptors, adhesion, secretion

    (Methods in enzymology ; 215)

    1992  

    Author's details ed. by Jacek Hawiger
    Series title Methods in enzymology ; 215
    Platelets
    Collection Platelets
    Language English
    Size XXVII, 526 S. : Ill., graph. Darst.
    Edition 1. [Dr.]
    Publisher Acad. Pr
    Publishing place San Diego u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT004354462
    ISBN 0-12-182116-1 ; 978-0-12-182116-6
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Shelf markLoan statusLocation
    928/2030 available for loan (reading room) Freihandmagazin (U1)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Book: Platelets / A

    Hawiger, Jacek

    receptors, adhesion, secretion

    (Methods in enzymology ; 169)

    1989  

    Author's details ed. by Jacek Hawiger
    Series title Methods in enzymology ; 169
    Platelets
    Collection Platelets
    Language English
    Size XXVIII, 512 S. : Ill., graph. Darst.
    Edition 1. [Dr.]
    Publisher Acad. Pr
    Publishing place San Diego u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT003290151
    ISBN 0-12-182070-X ; 978-0-12-182070-1
    Database Catalogue ZB MED Medicine, Health

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    Se 222 -169- verfügbar in Königswinter Königswinter

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Book: Platelets / A

    Hawiger, Jacek

    receptors, adhesion, secretion

    (Methods in enzymology ; 169)

    1989  

    Author's details ed. by Jacek Hawiger
    Series title Methods in enzymology ; 169
    Platelets
    Collection Platelets
    Language English
    Size XXVIII, 512 S. : Ill., graph. Darst.
    Edition 1. [Dr.]
    Publisher Acad. Pr
    Publishing place San Diego u.a.
    Publishing country United States
    Document type Book
    HBZ-ID HT003290151
    ISBN 0-12-182070-X ; 978-0-12-182070-1
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Shelf markLoan statusLocation
    908/554 order for loan Geschlossenes Magazin (U2)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: Decoding inflammation, its causes, genomic responses, and emerging countermeasures.

    Hawiger, Jacek / Zienkiewicz, Jozef

    Scandinavian journal of immunology

    2019  Volume 90, Issue 6, Page(s) e12812

    Abstract: Inflammation is the mechanism of diseases caused by microbial, autoimmune, allergic, metabolic and physical insults that produce distinct types of inflammatory responses. This aetiologic view of inflammation informs its classification based on a cause- ... ...

    Abstract Inflammation is the mechanism of diseases caused by microbial, autoimmune, allergic, metabolic and physical insults that produce distinct types of inflammatory responses. This aetiologic view of inflammation informs its classification based on a cause-dependent mechanism as well as a cause-directed therapy and prevention. The genomic era ushered in a new understanding of inflammation by highlighting the cell's nucleus as the centre of the inflammatory response. Exogenous or endogenous inflammatory insults evoke genomic responses in immune and non-immune cells. These genomic responses depend on transcription factors, which switch on and off a myriad of inflammatory genes through their regulatory networks. We discuss the transcriptional paradigm of inflammation based on denying transcription factors' access to the nucleus. We present two approaches that control proinflammatory signalling to the nucleus. The first approach constitutes a novel intracellular protein therapy with bioengineered physiologic suppressors of cytokine signalling. The second approach entails control of proinflammatory transcriptional cascades by targeting nuclear transport with a cell-penetrating peptide that inhibits the expression of 23 out of the 26 mediators of inflammation along with the nine genes required for metabolic responses. We compare these emerging anti-inflammatory countermeasures to current therapies. The transcriptional paradigm of inflammation offers nucleocentric strategies for microbial, autoimmune, metabolic, physical and other types of inflammation afflicting millions of people worldwide.
    MeSH term(s) Animals ; Biomarkers ; Disease Management ; Disease Susceptibility ; Gene Expression Regulation ; Genomics/methods ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation/diagnosis ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/therapy ; Metabolic Networks and Pathways/genetics ; Molecular Targeted Therapy ; Signal Transduction
    Chemical Substances Biomarkers
    Language English
    Publishing date 2019-08-28
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 120476-2
    ISSN 1365-3083 ; 0300-9475
    ISSN (online) 1365-3083
    ISSN 0300-9475
    DOI 10.1111/sji.12812
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 806: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice.

    Chiusa, Manuel / Lee, Youngmin A / Zhang, Ming-Zhi / Harris, Raymond C / Sherrill, Taylor / Lindner, Volkhard / Brooks, Craig R / Yu, Gang / Fogo, Agnes B / Flynn, Charles R / Zienkiewicz, Jozef / Hawiger, Jacek / Zent, Roy / Pozzi, Ambra

    The Journal of clinical investigation

    2024  Volume 134, Issue 6

    Abstract: Uncontrolled accumulation of extracellular matrix leads to tissue fibrosis and loss of organ function. We previously demonstrated in vitro that the DNA/RNA-binding protein fused in sarcoma (FUS) promotes fibrotic responses by translocating to the nucleus, ...

    Abstract Uncontrolled accumulation of extracellular matrix leads to tissue fibrosis and loss of organ function. We previously demonstrated in vitro that the DNA/RNA-binding protein fused in sarcoma (FUS) promotes fibrotic responses by translocating to the nucleus, where it initiates collagen gene transcription. However, it is still not known whether FUS is profibrotic in vivo and whether preventing its nuclear translocation might inhibit development of fibrosis following injury. We now demonstrate that levels of nuclear FUS are significantly increased in mouse models of kidney and liver fibrosis. To evaluate the direct role of FUS nuclear translocation in fibrosis, we used mice that carry a mutation in the FUS nuclear localization sequence (FUSR521G) and the cell-penetrating peptide CP-FUS-NLS that we previously showed inhibits FUS nuclear translocation in vitro. We provide evidence that FUSR521G mice or CP-FUS-NLS-treated mice showed reduced nuclear FUS and fibrosis following injury. Finally, differential gene expression analysis and immunohistochemistry of tissues from individuals with focal segmental glomerulosclerosis or nonalcoholic steatohepatitis revealed significant upregulation of FUS and/or collagen genes and FUS protein nuclear localization in diseased organs. These results demonstrate that injury-induced nuclear translocation of FUS contributes to fibrosis and highlight CP-FUS-NLS as a promising therapeutic option for organ fibrosis.
    MeSH term(s) Animals ; Mice ; RNA ; RNA-Binding Protein FUS/genetics ; RNA-Binding Protein FUS/metabolism ; DNA-Binding Proteins/genetics ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Mutation ; DNA ; Fibrosis ; Collagen/metabolism ; Amyotrophic Lateral Sclerosis/genetics
    Chemical Substances RNA (63231-63-0) ; RNA-Binding Protein FUS ; DNA-Binding Proteins ; RNA-Binding Proteins ; DNA (9007-49-2) ; Collagen (9007-34-5)
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI175158
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in Destabilization of Adherens Junctions.

    Wylezinski, Lukasz S / Hawiger, Jacek

    The Journal of biological chemistry

    2016  Volume 291, Issue 44, Page(s) 22913–22923

    Abstract: The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier and alters brain microcirculation, underlying vascular leak syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the ... ...

    Abstract The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier and alters brain microcirculation, underlying vascular leak syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been determined previously. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex. Then we established that signaling through this receptor complex leads to activation of the transcription factor, nuclear factor κB, resulting in expression of proinflammatory interleukin 6 and monocyte chemoattractant protein 1. We also discovered that IL2 induces disruption of adherens junctions, concomitant with cytoskeletal reorganization, ultimately leading to increased endothelial cell permeability. IL2-induced phosphorylation of vascular endothelial cadherin (VE-cadherin), a constituent of adherens junctions, leads to dissociation of its stabilizing adaptor partners, p120-catenin and β-catenin. Increased phosphorylation of VE-cadherin was also accompanied by a reduction of Src homology 2 domain-containing protein-tyrosine phosphatase 2, known to maintain vascular barrier function. These results unravel the mechanism of deleterious effects induced by IL2 on brain microvascular endothelial cells and may inform the development of new measures to improve IL2 cancer immunotherapy, as well as treatments for autoimmune diseases affecting the central nervous system.
    MeSH term(s) Adherens Junctions/metabolism ; Animals ; Blood-Brain Barrier/metabolism ; Brain/blood supply ; Brain/metabolism ; Capillary Permeability ; Cells, Cultured ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism ; Endothelial Cells/metabolism ; Humans ; Interleukin-2/adverse effects ; Interleukin-2/genetics ; Interleukin-2/metabolism ; Mice ; Microvessels/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Signal Transduction ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances Chemokine CCL2 ; Interleukin-2 ; NF-kappa B ; beta Catenin
    Language English
    Publishing date 2016-09-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M116.729038
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top