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EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis
H. Lu, L. Xie, L. Guo, X. Gu, R. Zhu, Y. Yang, F. Tang, M. Li, C. Liu, D. Wang, M. Li, Y. Tian, S. Cai
Jazyk angličtina Země Irsko
Typ dokumentu časopisecké články
- MeSH
- katechin * analogy a deriváty farmakologie MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory pánve * radioterapie MeSH
- proteinkinasy aktivované AMP metabolismus MeSH
- radiační poranění * prevence a kontrola MeSH
- radioprotektivní látky farmakologie terapeutické užití MeSH
- střeva účinky záření účinky léků mikrobiologie MeSH
- střevní mikroflóra * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII. MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing. RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK. CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.
Citace poskytuje Crossref.org
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- $a Lu, Haiyan $u Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
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- $a BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII. MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing. RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK. CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.
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- $a Xie, Liwei $u Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China
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- $a Wang, Difan $u Suzhou Medical College of Soochow University, Suzhou 215000, China
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- $a Li, Ming $u State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China. Electronic address: lim1984@suda.edu.cn
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- $a Tian, Ye $u Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: dryetian@126.com
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- $a Cai, Shang $u Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Center of PRaG therapy, Center for Cancer Diagnosis and Treatment, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: cbibbys@163.com
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