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  1. Article ; Online: Exosomal lncRNA HOTAIR promotes osteoclast differentiation by targeting TGF-β/PTHrP/RANKL pathway.

    Zhang, Chengcheng / Yang, Jiyong / Zhu, Zhiyao / Qin, Jingru / Yang, Lu / Zhao, Xiaoxue / Su, Wan / Cai, Yuejiao / Yang, Jia / Wang, Fengying / Chen, Wenlian / Gu, Honggang / Deng, Haibin / Wang, Zhongqi

    Basic & clinical pharmacology & toxicology

    2023  Volume 132, Issue 3, Page(s) 242–252

    Abstract: Bone tissue is a common metastatic site of lung cancer, and bone metastasis is characterized by abnormal differentiation and malfunction of osteoclast, and the roles of exosomes derived from lung cancer have attracted much attention. In our study, we ... ...

    Abstract Bone tissue is a common metastatic site of lung cancer, and bone metastasis is characterized by abnormal differentiation and malfunction of osteoclast, and the roles of exosomes derived from lung cancer have attracted much attention. In our study, we found that the level of HOTAIR expression in A549 and H1299 exosomes was higher than those of normal lung fibrocytes. Overexpression of HOTAIR in A549 and H1299 exosomes promoted osteoclast differentiation. Furthermore, A549-Exos and H1299-Exos targeted bone tissues, and bone formation was significantly inhibited in vivo. Mechanistically, exosomal lncRNA HOTAIR promoted bone resorption by targeting TGF-β/PTHrP/RANKL pathway.
    MeSH term(s) Humans ; Cell Differentiation/genetics ; Exosomes/genetics ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Osteoclasts/metabolism ; Parathyroid Hormone-Related Protein/metabolism ; RANK Ligand/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Transforming Growth Factor beta/metabolism
    Chemical Substances HOTAIR long untranslated RNA, human ; Parathyroid Hormone-Related Protein ; RANK Ligand ; RNA, Long Noncoding ; Transforming Growth Factor beta
    Language English
    Publishing date 2023-01-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2134679-3
    ISSN 1742-7843 ; 1742-7835
    ISSN (online) 1742-7843
    ISSN 1742-7835
    DOI 10.1111/bcpt.13823
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Active post-transcriptional regulation and ACLY-mediated acetyl-CoA synthesis as a pivotal target of Shuang-Huang-Sheng-Bai formula for lung adenocarcinoma treatment.

    Liu, Dan / Dong, Changsheng / Wang, Fengying / Liu, Wei / Jin, Xing / Qi, Sheng-Lan / Liu, Lei / Jin, Qiang / Wang, Siliang / Wu, Jia / Wang, Congcong / Yang, Jing / Deng, Haibin / Cai, Yuejiao / Yang, Lu / Qin, Jingru / Zhang, Chengcheng / Yang, Xi / Wang, Ming-Song /
    Yu, Guanzhen / Xue, Yu-Wen / Wang, Zhongqi / Ge, Guang-Bo / Xu, Zhenye / Chen, Wen-Lian

    Phytomedicine : international journal of phytotherapy and phytopharmacology

    2023  Volume 113, Page(s) 154732

    Abstract: Background: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC ... ...

    Abstract Background: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear.
    Purpose: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target.
    Methods: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB.
    Results: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication.
    Conclusion: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.
    MeSH term(s) Humans ; Mice ; Animals ; ATP Citrate (pro-S)-Lyase/genetics ; ATP Citrate (pro-S)-Lyase/metabolism ; Acetyl Coenzyme A/metabolism ; Drugs, Chinese Herbal/pharmacology ; Adenocarcinoma of Lung/drug therapy ; Lung Neoplasms/drug therapy
    Chemical Substances ATP Citrate (pro-S)-Lyase (EC 2.3.3.8) ; Acetyl Coenzyme A (72-89-9) ; Drugs, Chinese Herbal
    Language English
    Publishing date 2023-02-26
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1205240-1
    ISSN 1618-095X ; 0944-7113
    ISSN (online) 1618-095X
    ISSN 0944-7113
    DOI 10.1016/j.phymed.2023.154732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone inhibits cell proliferation, invasion, and migration in gastric cancer in part via autophagy.

    Wan, Boshun / Zhu, Junqiu / Chang, Qing / Zhou, Haihua / Shi, Zhan / Min, Li / Cai, YueJiao / Guan, Honggeng

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2018  Volume 98, Page(s) 709–718

    Abstract: Gastric cancer is a leading cause of mortality worldwide. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human ... ...

    Abstract Gastric cancer is a leading cause of mortality worldwide. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human carcinoma cell lines. In this study, we investigated the anti-cancer ability of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone and its underlying mechanism in MKN45 cells. Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone induced excess reactive oxygen species (ROS) accumulation. Transwell and wound healing assays demonstrated that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone inhibited the invasion and migration ability of MKN45 cells. Moreover, autophagy-related proteins Beclin-1, Atg5, and Atg7 were up-regulated. Light chain 3 (LC3)-I protein was converted into LC3-II under alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone exposure. Transmission electron microscopy demonstrated that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone treatment resulted in the formation of autophagosomes. Immunofluorescence assays suggested that alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone treatment elicited dot formation of green fluorescent protein (GFP)-LC3. 3-methyladenine (3-MA), an autophagy inhibitor, demonstrated that autophagy promoted death in MKN45 cells. Western blotting showed that ROS/mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways play crucial roles in the intrinsic mechanism of alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone's activity. The combined use of N-acetyl-
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacology ; Apoptosis Regulatory Proteins/metabolism ; Autophagy/drug effects ; Beclin-1/metabolism ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Chalcones/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Mice ; Mice, Nude ; Microtubule-Associated Proteins/metabolism ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Neoplasm Invasiveness/prevention & control ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/metabolism
    Chemical Substances Antineoplastic Agents ; Apoptosis Regulatory Proteins ; Beclin-1 ; Chalcones ; Microtubule-Associated Proteins ; Reactive Oxygen Species ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; dihydrochalcone (H5W525SX7Q)
    Language English
    Publishing date 2018-02
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2017.12.081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: [Diagnosis and treatment of intestinal stone obstruction in infants by combined use of ultrathin gastroscopy and enteroscopy].

    Jiang, Gui-jun / Fang, Mei / Ji, Cheng-hong / Shen, Tong / Fang, Hui-gi / Zhu, Zhong-mei / Cai, Yue-jiao / Zhan, Na-ping

    Zhonghua er ke za zhi = Chinese journal of pediatrics

    2003  Volume 41, Issue 3, Page(s) 167

    MeSH term(s) Female ; Gastroscopy ; Humans ; Infant ; Intestinal Obstruction/diagnosis ; Intestinal Obstruction/therapy ; Treatment Outcome
    Language Chinese
    Publishing date 2003-03
    Publishing country China
    Document type Case Reports ; Journal Article
    ZDB-ID 784523-6
    ISSN 0578-1310
    ISSN 0578-1310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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