1.Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway.
Shuhua SHAN ; Jinping NIU ; Ruopeng YIN ; Jiangying SHI ; Lizhen ZHANG ; Caihong WU ; Hanqing LI ; Zhuoyu LI
Acta Pharmaceutica Sinica B 2022;12(3):1254-1270
Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
2.Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms.
Ruopeng YIN ; Tao WANG ; Huanqin DAI ; Junjie HAN ; Jingzu SUN ; Ningning LIU ; Wang DONG ; Jin ZHONG ; Hongwei LIU
Protein & Cell 2023;14(10):776-785
Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.
Gastrointestinal Microbiome
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Intestinal Mucosa
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Bacteria
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Immune System
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Symbiosis
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Immunity, Mucosal
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Immunity, Innate