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  1. Article ; Online: The Inovirus Pf4 Triggers Antiviral Responses and Disrupts the Proliferation of Airway Basal Epithelial Cells.

    Popescu, Medeea C / Haddock, Naomi L / Burgener, Elizabeth B / Rojas-Hernandez, Laura S / Kaber, Gernot / Hargil, Aviv / Bollyky, Paul L / Milla, Carlos E

    Viruses

    2024  Volume 16, Issue 1

    Abstract: Background: The inovirus Pf4 is a lysogenic bacteriophage of : Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional ...

    Abstract Background: The inovirus Pf4 is a lysogenic bacteriophage of
    Methods: Primary BCs isolated from pwCF and wild-type (WT) donors were cultured in vitro and exposed to Pf4 or bacterial Lipopolysaccharide (LPS) followed by transcriptomic and functional assays.
    Results: We found that BCs internalized Pf4 and this elicits a strong antiviral response as well as neutrophil chemokine production. Further, we found that BCs that take up Pf4 demonstrate defective migration and proliferation.
    Conclusions: Our findings are highly suggestive of Pf4 playing a role in the pathogenicity of
    MeSH term(s) Animals ; Humans ; Respiratory System ; Epithelial Cells ; Epithelium ; Cystic Fibrosis ; Cell Proliferation ; Antiviral Agents ; Pseudomonas aeruginosa/physiology ; Pseudomonas Infections/microbiology ; Mammals
    Chemical Substances Antiviral Agents
    Language English
    Publishing date 2024-01-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v16010165
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bacterial outer membrane vesicles bound to bacteriophages modulate neutrophil responses to bacterial infection.

    Pennetzdorfer, Nina / Popescu, Medeea C / Haddock, Naomi L / Dupuy, Fannie / Kaber, Gernot / Hargil, Aviv / Johansson, Patrik K / Enejder, Annika / Bollyky, Paul L

    Frontiers in cellular and infection microbiology

    2023  Volume 13, Page(s) 1250339

    Abstract: Pseudomonas ... ...

    Abstract Pseudomonas aeruginosa
    MeSH term(s) Humans ; Animals ; Mice ; Neutrophils/metabolism ; Bacteriophages ; Bacterial Outer Membrane/metabolism ; Toll-Like Receptor 3 ; Pseudomonas Infections/microbiology ; Endotoxins ; Mammals
    Chemical Substances Toll-Like Receptor 3 ; Endotoxins
    Language English
    Publishing date 2023-10-26
    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 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2023.1250339
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Recommendations for the Equitable and Widespread Implementation of Liquid Biopsy for Cancer Care.

    Febbo, Phillip G / Allo, Mina / Alme, Emma B / Cuyun Carter, Gebra / Dumanois, Robert / Essig, Alessia / Kiernan, Estevan / Kubler, Caitlin B / Martin, Nikki / Popescu, Medeea C / Leiman, Lauren C

    JCO precision oncology

    2024  Volume 8, Page(s) e2300382

    Abstract: Liquid biopsies-tests that detect circulating tumor cellular components in the bloodstream-have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring. Today, liquid biopsies are being used to guide ... ...

    Abstract Liquid biopsies-tests that detect circulating tumor cellular components in the bloodstream-have the potential to transform cancer by reducing health inequities in screening, diagnostics, and monitoring. Today, liquid biopsies are being used to guide treatment choices for patients and monitor for cancer recurrence, and promising work in multi-cancer early detection is ongoing. However, without awareness of the barriers to adoption of this new technology and a willingness to build mitigation efforts into the implementation of widespread liquid biopsy testing, the communities that could most benefit may be the last to access and use them. In this work, we review the challenges likely to affect the accessibility of liquid biopsies in both the general population and underserved populations, and recommend specific actions to facilitate equitable access for all patients.
    MeSH term(s) Humans ; Liquid Biopsy ; Neoplastic Cells, Circulating
    Language English
    Publishing date 2024-01-24
    Publishing country United States
    Document type Review ; Journal Article
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.23.00382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices.

    Adebowale, Kolade / Ha, Byunghang / Saraswathibhatla, Aashrith / Indana, Dhiraj / Popescu, Medeea C / Demirdjian, Sally / Yang, Jin / Bassik, Michael C / Franck, Christian / Bollyky, Paul L / Chaudhuri, Ovijit

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Circulating monocytes are recruited to the tumor microenvironment, where they can differentiate into macrophages that mediate tumor progression. To reach the tumor microenvironment, monocytes must first extravasate and migrate through the type-1 collagen ...

    Abstract Circulating monocytes are recruited to the tumor microenvironment, where they can differentiate into macrophages that mediate tumor progression. To reach the tumor microenvironment, monocytes must first extravasate and migrate through the type-1 collagen rich stromal matrix. The viscoelastic stromal matrix around tumors not only stiffens relative to normal stromal matrix, but often exhibits enhanced viscous characteristics, as indicated by a higher loss tangent or faster stress relaxation rate. Here, we studied how changes in matrix stiffness and viscoelasticity, impact the three-dimensional migration of monocytes through stromal-like matrices. Interpenetrating networks of type-1 collagen and alginate, which enable independent tunability of stiffness and stress relaxation over physiologically relevant ranges, were used as confining matrices for three-dimensional culture of monocytes. Increased stiffness and faster stress relaxation independently enhanced the 3D migration of monocytes. Migrating monocytes have an ellipsoidal or rounded wedge-like morphology, reminiscent of amoeboid migration, with accumulation of actin at the trailing edge. Matrix adhesions and Rho-mediated contractility were dispensable for monocyte migration in 3D, but migration did require actin polymerization and myosin contractility. Mechanistic studies indicate that actin polymerization at the leading edge generates protrusive forces that open a path for the monocytes to migrate through in the confining viscoelastic matrices. Taken together, our findings implicate matrix stiffness and stress relaxation as key mediators of monocyte migration and reveal how monocytes use pushing forces at the leading edge mediated by actin polymerization to generate migration paths in confining viscoelastic matrices.
    Significance statement: Cell migration is essential for numerous biological processes in health and disease, including for immune cell trafficking. Monocyte immune cells migrate through extracellular matrix to the tumor microenvironment where they can play a role in regulating cancer progression. Increased extracellular matrix (ECM) stiffness and viscoelasticity have been implicated in cancer progression, but the impact of these changes in the ECM on monocyte migration remains unknown. Here, we find that increased ECM stiffness and viscoelasticity promote monocyte migration. Interestingly, we reveal a previously undescribed adhesion-independent mode of migration whereby monocytes generate a path to migrate through pushing forces at the leading edge. These findings help elucidate how changes in the tumor microenvironment impact monocyte trafficking and thereby disease progression.
    Language English
    Publishing date 2023-06-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.09.544394
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The phosphorylation state of both hERG and KvLQT1 mediates protein-protein interactions between these complementary cardiac potassium channel alpha subunits.

    Popescu, Medeea C / Lee, Yeon J / Kim, Stephanie S / Wade, Heidi M / Papakyrikos, Amanda M / Darling, Louise E O

    Biochimica et biophysica acta. Biomembranes

    2021  Volume 1863, Issue 4, Page(s) 183556

    Abstract: KvLQT1 and hERG are the α-subunits of the voltage-gated ... ...

    Abstract KvLQT1 and hERG are the α-subunits of the voltage-gated K
    MeSH term(s) Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/metabolism ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; ERG1 Potassium Channel/genetics ; ERG1 Potassium Channel/metabolism ; HEK293 Cells ; Humans ; KCNQ1 Potassium Channel/genetics ; KCNQ1 Potassium Channel/metabolism ; Phosphorylation/genetics ; Transcriptional Regulator ERG/genetics ; Transcriptional Regulator ERG/metabolism
    Chemical Substances ERG protein, human ; ERG1 Potassium Channel ; KCNH2 protein, human ; KCNQ1 Potassium Channel ; KCNQ1 protein, human ; Transcriptional Regulator ERG ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
    Language English
    Publishing date 2021-01-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamem.2021.183556
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Filamentous bacteriophage delays healing of Pseudomonas-infected wounds.

    Bach, Michelle S / de Vries, Christiaan R / Khosravi, Arya / Sweere, Johanna M / Popescu, Medeea C / Chen, Qingquan / Demirdjian, Sally / Hargil, Aviv / Van Belleghem, Jonas D / Kaber, Gernot / Hajfathalian, Maryam / Burgener, Elizabeth B / Liu, Dan / Tran, Quynh-Lam / Dharmaraj, Tejas / Birukova, Maria / Sunkari, Vivekananda / Balaji, Swathi / Ghosh, Nandini /
    Mathew-Steiner, Shomita S / El Masry, Mohamed S / Keswani, Sundeep G / Banaei, Niaz / Nedelec, Laurence / Sen, Chandan K / Chandra, Venita / Secor, Patrick R / Suh, Gina A / Bollyky, Paul L

    Cell reports. Medicine

    2022  Volume 3, Issue 6, Page(s) 100656

    Abstract: Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models ... ...

    Abstract Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds.
    MeSH term(s) Animals ; Biofilms ; Humans ; Inovirus ; Mammals ; Prospective Studies ; Pseudomonas ; Pseudomonas Infections/therapy ; Pseudomonas aeruginosa ; Wound Healing ; Wound Infection/therapy
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2022.100656
    Database MEDical Literature Analysis and Retrieval System OnLINE

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