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  1. Article ; Online: Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases.

    Cheong, Dorothy H J / Tan, Daniel W S / Wong, Fred W S / Tran, Thai

    Pharmacological research

    2020  Volume 158, Page(s) 104901

    Abstract: Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its ... ...

    Abstract Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its endoperoxidase properties. Progressively, research has found that artemisinins displayed multiple pharmacological actions against inflammation, viral infections, and cell and tumour proliferation, making it effective against diseases. Moreover, it has displayed a relatively safe toxicity profile. The use of artemisinins against different respiratory diseases has been investigated in lung cancer models and inflammatory-driven respiratory disorders. These studies revealed the ability of artemisinins in attenuating proliferation, inflammation, invasion, and metastasis, and in inducing apoptosis. Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis. In this review, we aim to provide a comprehensive update of the current knowledge of the effects of artemisinins in relation to respiratory diseases to identify gaps that need to be filled in the course of repurposing artemisinins for the treatment of respiratory diseases. In addition, we postulate whether artemisinins can also be repurposed for the treatment of COVID-19 given its anti-viral and anti-inflammatory properties.
    MeSH term(s) Antiviral Agents/therapeutic use ; Artemisinins/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy ; Humans ; Lung Diseases/drug therapy ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2
    Chemical Substances Antiviral Agents ; Artemisinins ; artemisinin (9RMU91N5K2)
    Keywords covid19
    Language English
    Publishing date 2020-05-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2020.104901
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases

    Cheong, Dorothy H J / Tan, Daniel W S / Wong, Fred W S / Tran, Thai

    Pharmacol Res

    Abstract: Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its ... ...

    Abstract Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its endoperoxidase properties. Progressively, research has found that artemisinins displayed multiple pharmacological actions against inflammation, viral infections, and cell and tumour proliferation, making it effective against diseases. Moreover, it has displayed a relatively safe toxicity profile. The use of artemisinins against different respiratory diseases has been investigated in lung cancer models and inflammatory-driven respiratory disorders. These studies revealed the ability of artemisinins in attenuating proliferation, inflammation, invasion, and metastasis, and in inducing apoptosis. Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis. In this review, we aim to provide a comprehensive update of the current knowledge of the effects of artemisinins in relation to respiratory diseases to identify gaps that need to be filled in the course of repurposing artemisinins for the treatment of respiratory diseases. In addition, we postulate whether artemisinins can also be repurposed for the treatment of COVID-19 given its anti-viral and anti-inflammatory properties.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #244950
    Database COVID19

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  3. Article ; Online: Molecular targets and anti-cancer potential of escin.

    Cheong, Dorothy H J / Arfuso, Frank / Sethi, Gautam / Wang, Lingzhi / Hui, Kam Man / Kumar, Alan Prem / Tran, Thai

    Cancer letters

    2018  Volume 422, Page(s) 1–8

    Abstract: Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More ... ...

    Abstract Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. Importantly, escin augments the effects of existing chemotherapeutic drugs, thereby supporting the role of escin as an adjunct or alternative anti-cancer therapy. The beneficial effects of escin can be attributed to its inhibition of proliferation and induction of cell cycle arrest. By regulating transcription factors/growth factors mediated oncogenic pathways, escin also potentially mitigates chronic inflammatory processes that are linked to cancer survival and resistance. This review provides a comprehensive overview of the current knowledge of escin and its potential as an anti-cancer therapy through its anti-proliferative, pro-apoptotic, and anti-inflammatory effects.
    MeSH term(s) Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Biomarkers, Tumor ; Cell Cycle Checkpoints/drug effects ; Cell Proliferation/drug effects ; Clinical Studies as Topic ; Drug Evaluation, Preclinical ; Escin/chemistry ; Escin/pharmacology ; Escin/therapeutic use ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology
    Chemical Substances Antineoplastic Agents ; Biomarkers, Tumor ; Escin (6805-41-0)
    Language English
    Publishing date 2018-02-21
    Publishing country Ireland
    Document type Journal Article ; Review
    ZDB-ID 195674-7
    ISSN 1872-7980 ; 0304-3835
    ISSN (online) 1872-7980
    ISSN 0304-3835
    DOI 10.1016/j.canlet.2018.02.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Integrin α7 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells.

    Teoh, Chun Ming / Tan, Sheryl S L / Langenbach, Shenna Y / Wong, Amanda H / Cheong, Dorothy H J / Tam, John K C / New, Chih Sheng / Tran, Thai

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 9892

    Abstract: Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as ... ...

    Abstract Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as novel therapeutic targets for asthma treatment. We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma. We now determine whether inhibition of integrin α7 expression would revert ASM cells back to a proliferative phenotype to cause an increase in ASM cell mass. This would be detrimental to asthmatic patients who already exhibit increased ASM mass in their airways. Using immunohistochemical analysis of the Melbourne Epidemiological Study of Childhood Asthma (MESCA) cohort, we show for the first time that integrin α7 expression in patients with severe asthma is increased, supporting a clinically relevant role for this protein in asthma pathophysiology. Moreover, inhibition of the laminin-integrin α7 signaling axis results in a reduction in smooth muscle-alpha actin abundance and does not revert ASM cells back to a proliferative phenotype. We determined that integrin α7-induced Kras isoform of p21 Ras acts as a point of convergence between contractile and proliferative ASM phenotypic states. Our study provides further support for targeting integrin α7 for the development of novel anti-asthma therapies.
    MeSH term(s) Antigens, CD/genetics ; Antigens, CD/metabolism ; Asthma/genetics ; Asthma/metabolism ; Asthma/pathology ; Biomarkers/metabolism ; Humans ; Integrin alpha Chains/genetics ; Integrin alpha Chains/metabolism ; Muscle, Smooth/metabolism ; Muscle, Smooth/pathology ; Mutation ; Phenotype ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Respiratory System/metabolism ; Respiratory System/pathology ; Signal Transduction
    Chemical Substances Antigens, CD ; Biomarkers ; Integrin alpha Chains ; KRAS protein, human ; integrin alpha7 ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
    Language English
    Publishing date 2019-07-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46260-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Integrin α7 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells

    Chun Ming Teoh / Sheryl S. L. Tan / Shenna Y. Langenbach / Amanda H. Wong / Dorothy H. J. Cheong / John K. C. Tam / Chih Sheng New / Thai Tran

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been ... ...

    Abstract Abstract Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as novel therapeutic targets for asthma treatment. We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma. We now determine whether inhibition of integrin α7 expression would revert ASM cells back to a proliferative phenotype to cause an increase in ASM cell mass. This would be detrimental to asthmatic patients who already exhibit increased ASM mass in their airways. Using immunohistochemical analysis of the Melbourne Epidemiological Study of Childhood Asthma (MESCA) cohort, we show for the first time that integrin α7 expression in patients with severe asthma is increased, supporting a clinically relevant role for this protein in asthma pathophysiology. Moreover, inhibition of the laminin-integrin α7 signaling axis results in a reduction in smooth muscle-alpha actin abundance and does not revert ASM cells back to a proliferative phenotype. We determined that integrin α7-induced Kras isoform of p21 Ras acts as a point of convergence between contractile and proliferative ASM phenotypic states. Our study provides further support for targeting integrin α7 for the development of novel anti-asthma therapies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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