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  1. Article: Effects of a proprietary mixture of extracts from

    Sens-Albert, Carla / Weisenburger, Sabrina / König, Beatrix C / Melcher, Silas F / Scheyhing, Ulrike A M / Rollet, Karin / Lluel, Philippe / Koch, Egon / Lehner, Martin D / Michel, Martin C

    Frontiers in pharmacology

    2024  Volume 15, Page(s) 1379456

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2024-03-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2024.1379456
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Zyxin protects from hypertension-induced cardiac dysfunction.

    Al-Hasani, Jaafar / Sens-Albert, Carla / Ghosh, Subhajit / Trogisch, Felix A / Nahar, Taslima / Friede, Prisca A P / Reil, Jan-Christian / Hecker, Markus

    Cellular and molecular life sciences : CMLS

    2022  Volume 79, Issue 2, Page(s) 93

    Abstract: Arterial hypertension causes left ventricular hypertrophy leading to dilated cardiomyopathy. Following compensatory cardiomyocyte hypertrophy, cardiac dysfunction develops due to loss of cardiomyocytes preceded or paralleled by cardiac fibrosis. Zyxin ... ...

    Abstract Arterial hypertension causes left ventricular hypertrophy leading to dilated cardiomyopathy. Following compensatory cardiomyocyte hypertrophy, cardiac dysfunction develops due to loss of cardiomyocytes preceded or paralleled by cardiac fibrosis. Zyxin acts as a mechanotransducer in vascular cells that may promote cardiomyocyte survival. Here, we analyzed cardiac function during experimental hypertension in zyxin knockout (KO) mice. In zyxin KO mice, made hypertensive by way of deoxycorticosterone acetate (DOCA)-salt treatment telemetry recording showed an attenuated rise in systolic blood pressure. Echocardiography indicated a systolic dysfunction, and isolated working heart measurements showed a decrease in systolic elastance. Hearts from hypertensive zyxin KO mice revealed increased apoptosis, fibrosis and an upregulation of active focal adhesion kinase as well as of integrins α5 and β1. Both interstitial and perivascular fibrosis were even more pronounced in zyxin KO mice exposed to angiotensin II instead of DOCA-salt. Stretched microvascular endothelial cells may release collagen 1α2 and TGF-β, which is characteristic for the transition to an intermediate mesenchymal phenotype, and thus spur the transformation of cardiac fibroblasts to myofibroblasts resulting in excessive scar tissue formation in the heart of hypertensive zyxin KO mice. While zyxin KO mice per se do not reveal a cardiac phenotype, this is unmasked upon induction of hypertension and owing to enhanced cardiomyocyte apoptosis and excessive fibrosis causes cardiac dysfunction. Zyxin may thus be important for the maintenance of cardiac function in spite of hypertension.
    MeSH term(s) Angiotensin II/toxicity ; Animals ; Apoptosis ; Blood Pressure ; Cardiomegaly/etiology ; Cardiomegaly/pathology ; Cardiomegaly/prevention & control ; Fibrosis/etiology ; Fibrosis/pathology ; Fibrosis/prevention & control ; Hypertension/chemically induced ; Hypertension/complications ; Hypertension/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/metabolism ; Zyxin/physiology
    Chemical Substances Zyxin ; Angiotensin II (11128-99-7)
    Language English
    Publishing date 2022-01-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04133-4
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 195: Show issues Location:
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  3. Article: Zyxin protects from hypertension-induced cardiac dysfunction

    Al-Hasani, Jaafar / Sens-Albert, Carla / Ghosh, Subhajit / Trogisch, Felix A. / Nahar, Taslima / Friede, Prisca A. P. / Reil, Jan-Christian / Hecker, Markus

    Cellular and molecular life sciences. 2022 Feb., v. 79, no. 2

    2022  

    Abstract: Arterial hypertension causes left ventricular hypertrophy leading to dilated cardiomyopathy. Following compensatory cardiomyocyte hypertrophy, cardiac dysfunction develops due to loss of cardiomyocytes preceded or paralleled by cardiac fibrosis. Zyxin ... ...

    Abstract Arterial hypertension causes left ventricular hypertrophy leading to dilated cardiomyopathy. Following compensatory cardiomyocyte hypertrophy, cardiac dysfunction develops due to loss of cardiomyocytes preceded or paralleled by cardiac fibrosis. Zyxin acts as a mechanotransducer in vascular cells that may promote cardiomyocyte survival. Here, we analyzed cardiac function during experimental hypertension in zyxin knockout (KO) mice. In zyxin KO mice, made hypertensive by way of deoxycorticosterone acetate (DOCA)-salt treatment telemetry recording showed an attenuated rise in systolic blood pressure. Echocardiography indicated a systolic dysfunction, and isolated working heart measurements showed a decrease in systolic elastance. Hearts from hypertensive zyxin KO mice revealed increased apoptosis, fibrosis and an upregulation of active focal adhesion kinase as well as of integrins α5 and β1. Both interstitial and perivascular fibrosis were even more pronounced in zyxin KO mice exposed to angiotensin II instead of DOCA-salt. Stretched microvascular endothelial cells may release collagen 1α2 and TGF-β, which is characteristic for the transition to an intermediate mesenchymal phenotype, and thus spur the transformation of cardiac fibroblasts to myofibroblasts resulting in excessive scar tissue formation in the heart of hypertensive zyxin KO mice. While zyxin KO mice per se do not reveal a cardiac phenotype, this is unmasked upon induction of hypertension and owing to enhanced cardiomyocyte apoptosis and excessive fibrosis causes cardiac dysfunction. Zyxin may thus be important for the maintenance of cardiac function in spite of hypertension.
    Keywords acetates ; apoptosis ; cardiac output ; cardiomyocytes ; cardiomyopathy ; collagen ; desoxycorticosterone ; echocardiography ; fibroblasts ; fibrosis ; hypertension ; hypertrophy ; integrins ; non-specific protein-tyrosine kinase ; phenotype ; systolic blood pressure ; telemetry
    Language English
    Dates of publication 2022-02
    Size p. 93.
    Publishing place Springer International Publishing
    Document type Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04133-4
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    In stock of ZB MED Bonn / Germany

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  4. Article ; Online: Characterisation of Lipoma-Preferred Partner as a Novel Mechanotransducer in Vascular Smooth Muscle Cells.

    Sporkova, Alexandra / Nahar, Taslima / Cao, Mingsi / Ghosh, Subhajit / Sens-Albert, Carla / Friede, Prisca Amayi Patricia / Nagel, Anika / Al-Hasani, Jaafar / Hecker, Markus

    Cells

    2023  Volume 12, Issue 18

    Abstract: In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have ... ...

    Abstract In arteries and arterioles, a chronic increase in blood pressure raises wall tension. This continuous biomechanical strain causes a change in gene expression in vascular smooth muscle cells (VSMCs) that may lead to pathological changes. Here we have characterised the functional properties of lipoma-preferred partner (LPP), a Lin11-Isl1-Mec3 (LIM)-domain protein, which is most closely related to the mechanotransducer zyxin but selectively expressed by smooth muscle cells, including VSMCs in adult mice. VSMCs isolated from the aorta of LPP knockout (LPP-KO) mice displayed a higher rate of proliferation than their wildtype (WT) counterparts, and when cultured as three-dimensional spheroids, they revealed a higher expression of the proliferation marker Ki 67 and showed greater invasion into a collagen gel. Accordingly, the gelatinase activity was increased in LPP-KO but not WT spheroids. The LPP-KO spheroids adhering to the collagen gel responded with decreased contraction to potassium chloride. The relaxation response to caffeine and norepinephrine was also smaller in the LPP-KO spheroids than in their WT counterparts. The overexpression of zyxin in LPP-KO VSMCs resulted in a reversal to a more quiescent differentiated phenotype. In native VSMCs, i.e., in isolated perfused segments of the mesenteric artery (MA), the contractile responses of LPP-KO segments to potassium chloride, phenylephrine or endothelin-1 did not vary from those in isolated perfused WT segments. In contrast, the myogenic response of LPP-KO MA segments was significantly attenuated while zyxin-deficient MA segments displayed a normal myogenic response. We propose that LPP, which we found to be expressed solely in the medial layer of different arteries from adult mice, may play an important role in controlling the quiescent contractile phenotype of VSMCs.
    MeSH term(s) Mice ; Animals ; Zyxin/metabolism ; Muscle, Smooth, Vascular/metabolism ; Potassium Chloride/metabolism ; Collagen/metabolism ; Transcription Factors/metabolism ; Myocytes, Smooth Muscle/metabolism ; Lipoma/metabolism ; Lipoma/pathology
    Chemical Substances Zyxin ; Potassium Chloride (660YQ98I10) ; Collagen (9007-34-5) ; Transcription Factors
    Language English
    Publishing date 2023-09-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12182315
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  5. Article ; Conference proceedings: Proanthocyandidines from EGb 761​: pharmacological effect on learning and memory and oral bioavailability

    Schmitt, Markus / Gantert, Thomas / Luderer, Gabriele / Kraus, Sebastian / Schneider, Heike / Kaiser, Simone / Becker, Anna-Franziska / Sens-Albert, Carla / Weisenburger, Sabrina / Kulić, Žarko / Martin Lehner, D.

    Planta Medica

    2023  Volume 89, Issue 14

    Event/congress 71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA), Trinity College Dublin Ireland, 2023-07-02
    Language English
    Publishing date 2023-11-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article ; Conference proceedings
    ZDB-ID 123545-x
    ISSN 1439-0221 ; 0032-0943
    ISSN (online) 1439-0221
    ISSN 0032-0943
    DOI 10.1055/s-0043-1773981
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    In stock of ZB MED Cologne/Königswinter

    Uf I Zs.157: Show issues Location:
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  6. Article ; Online: Significant improvement of bone marrow-derived MSC expansion from MDS patients by defined xeno-free medium.

    Altrock, Eva / Sens-Albert, Carla / Hofmann, Franziska / Riabov, Vladimir / Schmitt, Nanni / Xu, Qingyu / Jann, Johann-Christoph / Rapp, Felicitas / Steiner, Laurenz / Streuer, Alexander / Nowak, Verena / Obländer, Julia / Weimer, Nadine / Palme, Iris / Göl, Melda / Darwich, Ali / Wuchter, Patrick / Metzgeroth, Georgia / Jawhar, Mohamad /
    Hofmann, Wolf-Karsten / Nowak, Daniel

    Stem cell research & therapy

    2023  Volume 14, Issue 1, Page(s) 156

    Abstract: Background: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells ( ... ...

    Abstract Background: Robust and reliable in vitro and in vivo models of primary cells are necessary to study the pathomechanisms of Myelodysplastic Neoplasms (MDS) and identify novel therapeutic strategies. MDS-derived hematopoietic stem and progenitor cells (HSPCs) are reliant on the support of bone marrow (BM) derived mesenchymal stroma cells (MSCs). Therefore, isolation and expansion of MCSs are essential for successfully modeling this disease. For the clinical use of healthy MSCs isolated from human BM, umbilical cord blood or adipose tissue, several studies showed that xeno-free (XF) culture conditions resulted in superior growth kinetics compared to MSCs cultured in the presence of fetal bovine serum (FBS). In this present study, we investigate, whether the replacement of a commercially available MSC expansion medium containing FBS with a XF medium is beneficial for the expansion of MSCs derived from BM of MDS patients which are often difficult to cultivate.
    Methods: MSCs isolated from BM of MDS patients were cultured and expanded in MSC expansion medium with FBS or XF supplement. Subsequently, the impact of culture media on growth kinetics, morphology, immunophenotype, clonogenic potential, differentiation capacity, gene expression profiles and ability to engraft in immunodeficient mouse models was evaluated.
    Results: Significant higher cell numbers with an increase in clonogenic potential were observed during culture of MDS MSCs with XF medium compared to medium containing FBS. Differential gene expression showed an increase in transcripts associated with MSC stemness after expansion with XF. Furthermore, immunophenotypes of the MSCs and their ability to differentiate into osteoblasts, adipocytes or chondroblasts remained stable. MSCs expanded with XF media were similarly supportive for creating MDS xenografts in vivo as MSCs expanded with FBS.
    Conclusion: Our data indicate that with XF media, higher cell numbers of MDS MSCs can be obtained with overall improved characteristics in in vitro and in vivo experimental models.
    MeSH term(s) Animals ; Mice ; Humans ; Culture Media, Serum-Free ; Bone Marrow ; Cell Differentiation ; Mesenchymal Stem Cells/metabolism ; Adipose Tissue ; Cell Proliferation ; Cells, Cultured
    Chemical Substances Culture Media, Serum-Free
    Language English
    Publishing date 2023-06-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-023-03386-5
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  7. Article ; Online: Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies.

    Xu, Qingyu / Streuer, Alexander / Jann, Johann-Christoph / Altrock, Eva / Schmitt, Nanni / Flach, Johanna / Sens-Albert, Carla / Rapp, Felicitas / Wolf, Julia / Nowak, Verena / Weimer, Nadine / Obländer, Julia / Palme, Iris / Kuzina, Mariia / Jawhar, Ahmed / Darwich, Ali / Weis, Cleo-Aron / Marx, Alexander / Wuchter, Patrick /
    Costina, Victor / Jäger, Evelyn / Sperk, Elena / Neumaier, Michael / Fabarius, Alice / Metzgeroth, Georgia / Nolte, Florian / Steiner, Laurenz / Levkin, Pavel A / Jawhar, Mohamad / Hofmann, Wolf-Karsten / Riabov, Vladimir / Nowak, Daniel

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1497

    Abstract: Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl ... ...

    Abstract Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN.
    MeSH term(s) Humans ; Female ; Mice ; Animals ; Azacitidine/pharmacology ; Azacitidine/therapeutic use ; Erythropoiesis ; Protein-Lysine 6-Oxidase ; Hematopoietic Stem Cells ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/pathology ; Myeloproliferative Disorders/pathology ; Neoplasms/pathology
    Chemical Substances Azacitidine (M801H13NRU) ; Protein-Lysine 6-Oxidase (EC 1.4.3.13)
    Language English
    Publishing date 2023-03-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-37175-8
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  8. Article ; Online: Humanized three-dimensional scaffold xenotransplantation models for myelodysplastic syndromes.

    Altrock, Eva / Sens-Albert, Carla / Jann, Johann-Christoph / Flach, Johanna / Riabov, Vladimir / Schmitt, Nanni / Xu, Qingyu / Mehralivand, Arwin / Hecht, Anna / Steiner, Laurenz / Streuer, Alexander / Nowak, Verena / Obländer, Julia / Weimer, Nadine / Palme, Iris / Jawhar, Ahmed / Weis, Cleo-Aron / Weyer, Vanessa / Nolte, Florian /
    Jawhar, Mohamad / Metzgeroth, Georgia / Marx, Alexander / Groden, Christoph / Hofmann, Wolf-Karsten / Nowak, Daniel

    Experimental hematology

    2021  Volume 107, Page(s) 38–50

    Abstract: Patient-derived xenograft (PDX) models have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in myelodysplastic syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, ... ...

    Abstract Patient-derived xenograft (PDX) models have emerged as versatile preclinical platforms for investigation of functional pathomechanisms in myelodysplastic syndromes (MDS) and other myeloid neoplasms. However, despite increasingly improved methodology, engraftment efficiencies frequently remain low. Humanized three-dimensional scaffold models (ossicle xenotransplantation models) in immunocompromised mice have recently been found to enable improved engraftment rates of healthy and malignant human hematopoiesis. We therefore interrogated the feasibility of using four different three-dimensional ossicle-based PDX models for application with primary MDS samples. In a fully standardized comparison, we evaluated scaffold materials such as Gelfoam, extracellular matrix (ECM), and human or xenogenous bone substance in comparison to intrafemoral (IF) co-injection of bone marrow (BM)-derived mesenchymal stromal cells (MSCs) and CD34
    MeSH term(s) Animals ; Bone Marrow Cells/pathology ; Disease Models, Animal ; Hematopoiesis ; Hematopoietic Stem Cells/pathology ; Humans ; Mesenchymal Stem Cells/pathology ; Mice ; Myelodysplastic Syndromes/pathology ; Transplantation, Heterologous
    Language English
    Publishing date 2021-12-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 185107-x
    ISSN 1873-2399 ; 0531-5573 ; 0301-472X
    ISSN (online) 1873-2399
    ISSN 0531-5573 ; 0301-472X
    DOI 10.1016/j.exphem.2021.12.395
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 922: Show issues Location:
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