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  1. Article ; Online: Targeting Cx43 to Reduce the Severity of Pressure Ulcer Progression.

    Kwek, Milton Sheng Yi / Thangaveloo, Moogaambikai / Madden, Leigh E / Phillips, Anthony R J / Becker, David L

    Cells

    2023  Volume 12, Issue 24

    Abstract: In the skin, repeated incidents of ischemia followed by reperfusion can result in the breakdown of the skin and the formation of a pressure ulcer. Here we gently applied paired magnets to the backs of mice to cause ischemia for 1.5 h and then removed ... ...

    Abstract In the skin, repeated incidents of ischemia followed by reperfusion can result in the breakdown of the skin and the formation of a pressure ulcer. Here we gently applied paired magnets to the backs of mice to cause ischemia for 1.5 h and then removed them to allow reperfusion. The sterile inflammatory response generated within 4 h causes a stage 1 pressure ulcer with an elevation of the gap junction protein Cx43 in the epidermis. If this process is repeated the insult will result in a more severe stage 2 pressure ulcer with a breakdown of the epidermis 2-3 days later. After a single pinch, the elevation of Cx43 in the epidermis is associated with the inflammatory response with an increased number of neutrophils, HMGB1 (marker of necrosis) and RIP3 (responsible for necroptosis). Delivering Cx43 specific antisense oligonucleotides sub-dermally after a single insult, was able to significantly reduce the elevation of epidermal Cx43 protein expression and reduce the number of neutrophils and prevent the elevation of HMGB1 and RIP3. In a double pinch model, the Cx43 antisense treatment was able to reduce the level of inflammation, necroptosis, and the extent of tissue damage and progression to an open wound. This approach may be useful in reducing the progression of stage 1 pressure ulcers to stage 2.
    MeSH term(s) Mice ; Animals ; Connexin 43/metabolism ; Pressure Ulcer ; HMGB1 Protein ; Connexins/metabolism ; Ischemia
    Chemical Substances Connexin 43 ; HMGB1 Protein ; Connexins
    Language English
    Publishing date 2023-12-18
    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/cells12242856
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Characterisation of an ischemia reperfusion model for the formation of a stage I pressure ulcer in mouse skin.

    Kwek, Milton Sheng Yi / Thangaveloo, Moogaambikai / Hui, Sophia Lim Beng / Madden, Leigh E / Phillips, Anthony Rj / Becker, David L

    Journal of tissue viability

    2021  Volume 30, Issue 3, Page(s) 352–362

    Abstract: Pairs of magnets were applied to the loose skin on the backs of mice in order to cause ischemia for periods of 1.5, 2, 2.5 and 3 h followed by reperfusion. We found 1.5 h of ischemia resulted in the most reliable outcome of blanched skin but no redness ... ...

    Abstract Pairs of magnets were applied to the loose skin on the backs of mice in order to cause ischemia for periods of 1.5, 2, 2.5 and 3 h followed by reperfusion. We found 1.5 h of ischemia resulted in the most reliable outcome of blanched skin but no redness or skin breakdown. Histological analysis at 4 h of reperfusion showed, in the centre of the insult, condensed nuclei in the epidermis and sebaceous glands with a build up of neutrophils in the blood vessels, and a reduction in the number of fibroblasts. At 24 h, spongiosis was seen in the epidermis and pockets of neutrophils began to accumulate under it, as well as being scatted through the dermis. In the centre of the insult there was a loss of sebaceous gland nuclei and fibroblasts. Four days after the insult, spongiosis was reduced in the epidermis at the edge of the insult but enhanced in the centre and in hair follicles. Leukocytes were seen throughout the central dermis. At 8 days, spongiosis and epidermal thickness had reduced and fibroblasts were reappearing. However, blood vessels still had leukocytes lining the lumen. The gap junction protein connexin 43 was significantly elevated in the epidermis at 4 h and 24 h reperfusion. Ischemia of 1.5 h generates a sterile inflammatory reaction causing the loss of some cell types but leaving the epidermis intact reminiscent of a stage I pressure ulcer.
    MeSH term(s) Animals ; Disease Models, Animal ; Ischemia/complications ; Ischemia/physiopathology ; Mice ; Pressure/adverse effects ; Pressure Ulcer/etiology ; Pressure Ulcer/physiopathology ; Reperfusion/methods ; Reperfusion/standards ; Reperfusion/statistics & numerical data ; Skin/pathology ; Skin/physiopathology
    Language English
    Publishing date 2021-03-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 1282604-2
    ISSN 0965-206X
    ISSN 0965-206X
    DOI 10.1016/j.jtv.2021.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clarity Plus™ digital PCR: A novel platform for absolute quantification of SARS-CoV-2

    Tan, Shawn Yi Han / Kwek, Milton Sheng Yi / Low, Huiyu / Pang, Yan Ling Joy

    medRxiv

    Abstract: In recent years, the usage of digital polymerase chain reaction (dPCR) for various clinical applications has increased exponentially. Considering the growing demand for improved dPCR technology, the Clarity Plus™ dPCR system which features enhanced ... ...

    Abstract In recent years, the usage of digital polymerase chain reaction (dPCR) for various clinical applications has increased exponentially. Considering the growing demand for improved dPCR technology, the Clarity Plus™ dPCR system which features enhanced multiplexing capability and a wider dynamic range for nucleic acid analysis was recently launched. In this study, a dPCR assay optimized for use on Clarity Plus™ was evaluated for the absolute quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent responsible for the global coronavirus disease 2019 (COVID-19) outbreak. The assay demonstrated good inter- and intra- assay precision, accuracy, as well as excellent linearity across a range of over 6 orders of magnitude for target gene quantification. In addition, comparison of the assay on both dPCR and qPCR platforms revealed that dPCR exhibited a slightly higher sensitivity compared to its qPCR counterpart when quantifying SARS-CoV-2 at a lower concentration. Overall, the results showed that the dPCR assay is a reliable and effective approach for the absolute quantification of SARS-CoV-2 and can potentially be adopted as a molecular tool in applications such as detecting low viral loads in patients as well as in wastewater surveillance of COVID-19.
    Keywords covid19
    Language English
    Publishing date 2021-06-01
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.05.30.21256718
    Database COVID19

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  4. Article ; Online: Temporal pressure enhanced topical drug delivery through micropore formation.

    Lio, Daniel Chin Shiuan / Chia, Rui Ning / Kwek, Milton Sheng Yi / Wiraja, Christian / Madden, Leigh Edward / Chang, Hao / Khadir, S Mohideen Abdul / Wang, Xiaomeng / Becker, David L / Xu, Chenjie

    Science advances

    2020  Volume 6, Issue 22, Page(s) eaaz6919

    Abstract: Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain ... ...

    Abstract Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain type of drug. Here, we report an innovative methodology based on temporal pressure to enhance the penetration of all kinds of drugs, from small molecules to proteins and nanoparticles (up to 500 nm). The creation of micropores (~3 μm
    Keywords covid19
    Language English
    Publishing date 2020-05-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.aaz6919
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Temporal pressure enhanced topical drug delivery through micropore formation

    Lio, Daniel Chin Shiuan / Chia, Rui Ning / Kwek, Milton Sheng Yi / Wiraja, Christian / Madden, Leigh Edward / Chang, Hao / Khadir, S Mohideen Abdul / Wang, Xiaomeng / Becker, David L / Xu, Chenjie

    Sci. Adv

    Abstract: Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain ... ...

    Abstract Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain type of drug. Here, we report an innovative methodology based on temporal pressure to enhance the penetration of all kinds of drugs, from small molecules to proteins and nanoparticles (up to 500 nm). The creation of micropores (~3 µm2) on the epidermal layer through a temporal pressure treatment results in the elevated expression of gap junctions, and reduced expression of occludin tight junctions. A 1 min treatment of 0.28-MPa allows nanoparticles (up to 500 nm) and macromolecules (up to 20 kDa) to reach a depth of 430-µm into the dermal layer. Using, as an example, the delivery of insulin through topical application after the pressure treatment yields up to 80% drop in blood glucose in diabetic mice.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #32937426
    Database COVID19

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  6. Article: Chemical synthesis of N-peptidyl 2-pyrrolidinemethanethiol for peptide ligation

    Yang, Renliang / Qi, Le / Liu, Yanling / Ding, Yingjie / Kwek, Milton Sheng Yi / Liu, Chuan-Fa

    Tetrahedron letters. 2013 July 17, v. 54, no. 29

    2013  

    Abstract: Peptides carrying a C-terminal 2-pyrrolidinemethanethiol (PMT) unit were synthesized using 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS), and were shown to ligate efficiently with cysteinyl-peptides. This novel PMT-mediated ... ...

    Abstract Peptides carrying a C-terminal 2-pyrrolidinemethanethiol (PMT) unit were synthesized using 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS), and were shown to ligate efficiently with cysteinyl-peptides. This novel PMT-mediated ligation tolerated many different C-terminal residues and was successfully applied to a one-pot N-to-C sequential ligation reaction and the semi-synthesis of lysine 16 acetylated histone H4, demonstrating the utility of the method in peptide and protein synthesis.
    Keywords chemical reactions ; chemical structure ; histones ; lysine ; organic compounds ; peptides ; protein synthesis ; synthesis
    Language English
    Dates of publication 2013-0717
    Size p. 3777-3780.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 204287-3
    ISSN 1873-3581 ; 0040-4039
    ISSN (online) 1873-3581
    ISSN 0040-4039
    DOI 10.1016/j.tetlet.2013.05.013
    Database NAL-Catalogue (AGRICOLA)

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