5 results on '"Hang Yin Chu"'
Search Results
2. Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation
- Author
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Yuanyuan Yu, Luyao Wang, Shuaijian Ni, Dijie Li, Jin Liu, Hang Yin Chu, Ning Zhang, Meiheng Sun, Nanxi Li, Qing Ren, Zhenjian Zhuo, Chuanxin Zhong, Duoli Xie, Yongshu Li, Zong-Kang Zhang, Huarui Zhang, Mei Li, Zhenlin Zhang, Lin Chen, Xiaohua Pan, Weibo Xia, Shu Zhang, Aiping Lu, Bao-Ting Zhang, and Ge Zhang
- Subjects
Genetic Markers ,Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,Cardiovascular System ,General Biochemistry, Genetics and Molecular Biology ,Rats ,Mice ,Apolipoproteins E ,Bone Density ,Osteogenesis ,Bone Morphogenetic Proteins ,Animals ,Humans ,Female ,Adaptor Proteins, Signal Transducing - Abstract
Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin’s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE−/− mice and hSOSTki.ApoE−/− mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOSTki mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.
- Published
- 2022
3. Dickkopf-1: A Promising Target for Cancer Immunotherapy
- Author
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Hang Yin Chu, Zihao Chen, Luyao Wang, Zong-Kang Zhang, Xinhuan Tan, Shuangshuang Liu, Bao-Ting Zhang, Aiping Lu, Yuanyuan Yu, and Ge Zhang
- Subjects
musculoskeletal diseases ,0301 basic medicine ,medicine.medical_treatment ,Immunology ,Cell ,Review ,Wnt signaling pathway ,Immunomodulation ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Neoplasms ,Biomarkers, Tumor ,medicine ,cancer ,Animals ,Humans ,Immunology and Allergy ,Molecular Targeted Therapy ,Immune Checkpoint Inhibitors ,beta Catenin ,DKK1 ,business.industry ,immune surveillance ,Disease Management ,Cancer ,Immunotherapy ,RC581-607 ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Intercellular Signaling Peptides and Proteins ,immunotherapy ,Disease Susceptibility ,Immunologic diseases. Allergy ,business ,CD8 ,Signal Transduction - Abstract
Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.
- Published
- 2021
4. Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery
- Author
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Ning Zhang, Yuanyuan Yu, Bao-Ting Zhang, Hang Yin Chu, Ge Zhang, Zihao Chen, and Zong-Kang Zhang
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0301 basic medicine ,Angiogenesis ,medicine.medical_treatment ,Protein domain ,aptamers ,Connective tissue ,Review ,Biology ,anti-CTGF ,03 medical and health sciences ,Cell and Developmental Biology ,0302 clinical medicine ,Fibrosis ,domain structure ,medicine ,lcsh:QH301-705.5 ,integumentary system ,Drug discovery ,Growth factor ,fibrosis ,CTGF ,Cell Biology ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Wound healing ,CCN2 ,Developmental Biology - Abstract
Connective tissue growth factor (CTGF) is a key signaling and regulatory molecule involved in different biological processes, such as cell proliferation, angiogenesis, and wound healing, as well as multiple pathologies, such as tumor development and tissue fibrosis. Although the underlying mechanisms of CTGF remain incompletely understood, a commonly accepted theory is that the interactions between different protein domains in CTGF and other various regulatory proteins and ligands contribute to its variety of functions. Here, we highlight the structure of each domain of CTGF and its biology functions in physiological conditions. We further summarized main diseases that are deeply influenced by CTGF domains and the potential targets of these diseases. Finally, we address the advantages and disadvantages of current drugs targeting CTGF and provide the perspective for the drug discovery of the next generation of CTGF inhibitors based on aptamers.
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- 2020
5. Cathepsin K: The Action in and Beyond Bone
- Author
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Ge Zhang, Jun Lu, Jin Liu, Zeting Wu, Hang Yin Chu, Aiping Lyu, and Rongchen Dai
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0301 basic medicine ,Proteases ,Cathepsin K ,Osteoporosis ,Review ,Pharmacology ,Bone resorption ,Cell and Developmental Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Osteoclast ,medicine ,In patient ,lcsh:QH301-705.5 ,Cathepsin K inhibitor ,business.industry ,lung fibrosis ,Cell Biology ,medicine.disease ,osteoporosis ,cardiovascular diseases ,osteoarthritis ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,chemistry ,Drug development ,030220 oncology & carcinogenesis ,osteoclast ,business ,bone resorption ,Odanacatib ,Developmental Biology - Abstract
Cathepsin K (CatK) is one of the most potent proteases in lysosomal cysteine proteases family, of which main function is to mediate bone resorption. Currently, CatK is among the most attractive targets for anti-osteoporosis drug development. Although many pharmaceutical companies are working on the development of selective inhibitors for CatK, there is no FDA approved drug till now. Odanacatib (ODN) developed by Merck & Co. is the only CatK inhibitor candidate which demonstrated high therapeutic efficacy in patients with postmenopausal osteoporosis in Phase III clinical trials. Unfortunately, the development of ODN was finally terminated due to the cardio-cerebrovascular adverse effects. Therefore, it arouses concerns on the undesirable CatK inhibition in non-bone sites. It is known that CatK has far-reaching actions throughout various organs besides bone. Many studies have also demonstrated the involvement of CatK in various diseases beyond the musculoskeletal system. This review not only summarized the functional roles of CatK in bone and beyond bone, but also discussed the potential relevance of the CatK action beyond bone to the adverse effects of inhibiting CatK in non-bone sites.
- Published
- 2020
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