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  1. Artikel ; Online: The Extracts of Dendrobium Alleviate Dry Eye Disease in Rat Model by Regulating Aquaporin Expression and MAPKs/NF-κB Signalling.

    Ling, Jiawei / Chan, Chung-Lap / Ho, Chi-Yan / Gao, Xun / Tsang, Sin-Man / Leung, Ping-Chung / Hu, Jiang-Miao / Wong, Chun-Kwok

    International journal of molecular sciences

    2022  Band 23, Heft 19

    Abstract: Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger ... ...

    Abstract Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger the inflammatory cascade response, resulting in ocular surface inflammation. It has been shown that the active ingredients in Dendrobium, such as polysaccharides, alkaloids and phenols, have anti-inflammatory, anti-tumour and immunity-boosting effects, and Dendrobium officinale extract can improve glandular secretion function, increase salivary secretion and increase the expression level of water channel protein in salivary glands in patients with dry eye syndromes. We investigated the in vitro cytoprotective effect of Dendrobium extracts in sodium chloride induced hyperosmotic conditions in human cornea keratocytes (HKs). Results showed that Dendrobium officinale Kimura et Migo water extract (DOW) and Dendrobium loddigesii Rolfe water extract (DLW) could upregulate the expression of aquaporins (AQP)5 protein, thus exerting a repairing effect by promoting cell migration. Furthermore, oral administration of DOW and DLW enhanced tear production in rats and exerted a protective effect on ocular surface damage. DOW and DLW could upregulate the expression of AQP5 and mucin (muc)5ac proteins in the lacrimal gland and reduce the inflammatory response. DOW and DLW inhibited the activation of the corresponding mitogen-activated protein kinases (MAPK) and NF-KB pathway, thereby playing a role in improving dry eye symptoms. This study provides a new perspective on dry eye treatment, and DOW and DLW may be potential therapeutic agents for dry eye.
    Mesh-Begriff(e) Animals ; Anti-Inflammatory Agents/therapeutic use ; Aquaporin 5/metabolism ; Dendrobium/metabolism ; Dry Eye Syndromes/metabolism ; Humans ; Mitogen-Activated Protein Kinases/metabolism ; Mucins/metabolism ; NF-kappa B/metabolism ; Phenols/metabolism ; Polysaccharides/metabolism ; Rats ; Sodium Chloride/metabolism ; Tears/metabolism ; Water/metabolism
    Chemische Substanzen Anti-Inflammatory Agents ; Aquaporin 5 ; Mucins ; NF-kappa B ; Phenols ; Polysaccharides ; Water (059QF0KO0R) ; Sodium Chloride (451W47IQ8X) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Sprache Englisch
    Erscheinungsdatum 2022-09-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms231911195
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: C-terminal binding protein 2 is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma.

    Cheung, Coty Hing Yau / Cheng, Chi Keung / Leung, Kam Tong / Zhang, Chi / Ho, Chi Yan / Luo, Xi / Kam, Angel Yuet Fong / Xia, Tian / Wan, Thomas Shek Kong / Pitts, Herbert Augustus / Chan, Natalie Pui Ha / Cheung, Joyce Sin / Wong, Raymond Siu Ming / Zhang, Xiao-Bing / Ng, Margaret Heung Ling

    Blood advances

    2024  Band 8, Heft 9, Seite(n) 2217–2234

    Abstract: Abstract: Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal ... ...

    Abstract Abstract: Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered "undruggable," as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy.
    Mesh-Begriff(e) Animals ; Humans ; Mice ; Alcohol Oxidoreductases/metabolism ; Alcohol Oxidoreductases/antagonists & inhibitors ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Interferon Regulatory Factors/metabolism ; Interferon Regulatory Factors/genetics ; Multiple Myeloma/metabolism ; Multiple Myeloma/drug therapy ; Multiple Myeloma/pathology ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction/drug effects ; Tumor Suppressor Proteins/metabolism ; Co-Repressor Proteins/antagonists & inhibitors ; Co-Repressor Proteins/metabolism
    Chemische Substanzen Alcohol Oxidoreductases (EC 1.1.-) ; Interferon Regulatory Factors ; Proto-Oncogene Proteins c-myc ; Tumor Suppressor Proteins ; CTBP2 protein, human (EC 1.1.-) ; Co-Repressor Proteins
    Sprache Englisch
    Erscheinungsdatum 2024-02-27
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010218
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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