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  1. Article ; Online: Vascular underpinning of COVID-19

    Vanessa Wazny / Anthony Siau / Kan Xing Wu / Christine Cheung

    Open Biology, Vol 10, Iss

    2020  Volume 8

    Abstract: COVID-19 management guidelines have largely attributed critically ill patients who develop acute respiratory distress syndrome, to a systemic overproduction of pro-inflammatory cytokines. Cardiovascular dysfunction may also represent a primary phenomenon, ...

    Abstract COVID-19 management guidelines have largely attributed critically ill patients who develop acute respiratory distress syndrome, to a systemic overproduction of pro-inflammatory cytokines. Cardiovascular dysfunction may also represent a primary phenomenon, with increasing data suggesting that severe COVID-19 reflects a confluence of vascular dysfunction, thrombosis and dysregulated inflammation. Here, we first consolidate the information on localized microvascular inflammation and disordered cytokine release, triggering vessel permeability and prothrombotic conditions that play a central role in perpetuating the pathogenic COVID-19 cascade. Secondly, we seek to clarify the gateways which SARS-CoV-2, the causative COVID-19 virus, uses to enter host vascular cells. Post-mortem examinations of patients' tissues have confirmed direct viral endothelial infection within several organs. While there have been advances in single-cell RNA sequencing, endothelial cells across various vascular beds express low or undetectable levels of those touted SARS-CoV-2 entry factors. Emerging studies postulate alternative pathways and the apicobasal distribution of host cell surface factors could influence endothelial SARS-CoV-2 entry and replication. Finally, we provide experimental considerations such as endothelial polarity, cellular heterogeneity in organoids and shear stress dynamics in designing cellular models to facilitate research on viral-induced endothelial dysfunctions. Understanding the vascular underpinning of COVID-19 pathogenesis is crucial to managing outcomes and mortality.
    Keywords endothelial dysfunction ; virus ; vascular biology ; Biology (General) ; QH301-705.5 ; covid19
    Subject code 570
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Bioengineered three‐dimensional transparent eggshell as a chicken embryo experimentation platform for biomedical research

    Noreen Ishak / Marcus Chan / Sook C. Ang / Christine Cheung / Swee‐Hin Teoh

    Engineering Reports, Vol 2, Iss 1, Pp n/a-n/a (2020)

    2020  

    Abstract: The chicken embryo is widely used as an experimental model in the areas of regenerative medicine, tumor biology, and angiogenesis. Eggshell opacity and rigidity present restricted three‐dimensional (3D) viewing and accessibility to the embryo and its ... ...

    Abstract The chicken embryo is widely used as an experimental model in the areas of regenerative medicine, tumor biology, and angiogenesis. Eggshell opacity and rigidity present restricted three‐dimensional (3D) viewing and accessibility to the embryo and its circulatory network despite egg windowing. The ability to engineer an eggshell, which eliminates the opacity yet provides 3D access for manipulation is beneficial and would potentially make it enticing for the use of chicken embryo as a cheaper alternative vertebrate model. Here, we present the feasibility of fabricating a morphologically analogous transparent chicken eggshell made of polydimethylsiloxane using a biaxial rotation computer‐controlled bioreactor to achieve uniform thickness. By culturing chicken embryo in the bioengineered eggshell, we demonstrated success in meeting developmental milestones and its practicality as an experimental platform by visualizing both embryo and vasculature development using common laboratory imaging tools. Although the viability of the embryo in the bioengineered eggshell was lower than in the normal egg, this was attributed to the absence of calcium source. The bioengineered eggshell, in its initial stage of development, provides a platform to be used to investigate beyond gross observations of the embryo and vascular network in 3D optical clarity and its imaging capabilities has the potential to be extended to other imaging modalities. We have developed a transparent ex ovo eggshell, biomimicking the elliptical geometry to address the lack of 3D optical clarity contributed by the eggshell opacity. This retains the natural shape that may support the development of the chicken embryo and allows easy access to the embryo, its circulatory system and respective organ development in far reaching applications.
    Keywords bioengineering ; chicken embryo ; fabrication ; imaging ; rotation molding ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Electronic computers. Computer science ; QA75.5-76.95
    Subject code 515
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Modified CRISPR/Cas9 mediated generation of two MKK7 knockout human embryonic stem cell lines

    C.H. Cole Sims / Matias I. Autio / Adriana Buskin / Christine Cheung / Rakesh Heer / Roger S.Y. Foo / Xin Wang

    Stem Cell Research, Vol 52, Iss , Pp 102238- (2021)

    2021  

    Abstract: Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage ... ...

    Abstract Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage differentiation capacity. These cell lines are a useful resource for studying MKK7 function in humans.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy

    Kan Xing Wu / Natalie Jia Ying Yeo / Chun Yi Ng / Florence Wen Jing Chioh / Qiao Fan / Xianfeng Tian / Binxia Yang / Gunaseelan Narayanan / Hui Min Tay / Han Wei Hou / N. Ray Dunn / Xinyi Su / Chui Ming Gemmy Cheung / Christine Cheung

    BMC Biology, Vol 20, Iss 1, Pp 1-

    2022  Volume 21

    Abstract: Abstract Background Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of ... ...

    Abstract Abstract Background Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. Results We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. Conclusions Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.
    Keywords Endothelial dysfunction ; Glycocalyx ; Hyaluronidase-1 ; Polypoidal choroidal vasculopathy ; Age-related macular degeneration ; Biology (General) ; QH301-705.5
    Subject code 610 ; 616
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Book ; Thesis: Using CALIPSO and CloudSat satellite retrievals to evaluate low-level cloud parameterizations in ECHAM5 for cloud-climate feedbacks implications

    Nam, Christine Cheung-Wai

    (Berichte zur Erdsystemforschung ; 88)

    2011  

    Author's details Christine Cheung-Wai Nam
    Series title Berichte zur Erdsystemforschung ; 88
    Language English ; German
    Size X, 112 S., Ill., graph. Darst.
    Publisher Max-Planck-Inst. für Meteorologie
    Publishing place Hamburg
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Department Geowissenschaften, Diss.--Hamburg, 2010
    Note Zsfassung in dt. Sprache
    Database Former special subject collection: coastal and deep sea fishing

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  6. Book ; Thesis: Using CALIPSO and CloudSat satellite retrievals to evaluate low-level cloud parameterizations in ECHAM5 for cloud-climate feedbacks implications

    Nam, Christine Cheung-Wai

    (Berichte zur Erdsystemforschung ; 88)

    2011  

    Author's details Christine Cheung-Wai Nam
    Series title Berichte zur Erdsystemforschung ; 88
    Language English ; German
    Size X, 112 S., Ill., graph. Darst.
    Publisher Max-Planck-Inst. für Meteorologie
    Publishing place Hamburg
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Department Geowissenschaften, Diss.--Hamburg, 2010
    Note Zsfassung in dt. Sprache
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  7. Article ; Online: Myocardin overexpression is sufficient for promoting the development of a mature smooth muscle cell-like phenotype from human embryonic stem cells.

    Linda Raphel / Amarnath Talasila / Christine Cheung / Sanjay Sinha

    PLoS ONE, Vol 7, Iss 8, p e

    2012  Volume 44052

    Abstract: Myocardin is thought to have a key role in smooth muscle cell (SMC) development by acting on CArG-dependent genes. However, it is unclear whether myocardin-induced SMC maturation and increases in agonist-induced calcium signalling are also associated ... ...

    Abstract Myocardin is thought to have a key role in smooth muscle cell (SMC) development by acting on CArG-dependent genes. However, it is unclear whether myocardin-induced SMC maturation and increases in agonist-induced calcium signalling are also associated with increases in the expression of non-CArG-dependent SMC-specific genes. Moreover, it is unknown whether myocardin promotes SMC development from human embryonic stem cells.Findings The effects of adenoviral-mediated myocardin overexpression on SMC development in human ESC-derived embryoid bodies were investigated using immunofluorescence, flow cytometry and real time RT-PCR. Myocardin overexpression from day 10 to day 28 of embryoid body differentiation increased the number of smooth muscle α-actin(+) and smooth muscle myosin heavy chain(+) SMC-like cells and increased carbachol-induced contractile function. However, myocardin was found to selectively regulate only CArG-dependent SMC-specific genes. Nevertheless, myocardin expression appeared to be sufficient to specify the SMC lineage.Myocardin increases the development and maturation of SMC-like cells from human embryonic stem cells despite not activating the full repertoire of SMC genes. These findings have implications for vascular tissue engineering and other applications requiring large numbers of functional SMCs.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2012-01-01T00:00:00Z
    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: Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Christine Cheung / Yeek Teck Goh / Jingxian Zhang / Chenghan Wu / Ernesto Guccione

    Cell Reports, Vol 9, Iss 1, Pp 391-

    2014  Volume 401

    Abstract: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ) accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we ...

    Abstract There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ) accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden.
    Keywords Biology (General) ; QH301-705.5
    Subject code 571 ; 610
    Language English
    Publishing date 2014-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

    Florence WJ Chioh / Siew-Wai Fong / Barnaby E Young / Kan-Xing Wu / Anthony Siau / Shuba Krishnan / Yi-Hao Chan / Guillaume Carissimo / Louis LY Teo / Fei Gao / Ru San Tan / Liang Zhong / Angela S Koh / Seow-Yen Tan / Paul A Tambyah / Laurent Renia / Lisa FP Ng / David C Lye / Christine Cheung

    eLife, Vol

    2021  Volume 10

    Abstract: Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of ... ...

    Abstract Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.
    Keywords COVID-19 ; circulating endothelial cells ; cytokines ; endothelial activation ; immune effector cells ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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