Frontiers in Chemistry
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2020
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IF 3.693
Lin Xiaona,Shi Yongli,Yu ShaSha,Li Siyi,Li Wenhui,Li Meishuang,Chen Shengxi,Wang Yuanbo,Cong Mei
A novel polymer of poloxamer188-b-PCL was synthesized via a ring-opening polymerization. Fourier transform infrared spectroscopy (FTIR), Raman, and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained poloxamer188-b-PCL. The thermo-stability of poloxamer188 -b-PCL was carried out with a thermal gravimetric analyzer (TGA), and cytotoxicity was obtained using the CCK8 method. Cargo-free and curcumin (CUR)-loaded poloxamer188-b-PCL NPs were fabricated via the solvent evaporation method. The morphology, particle size distribution, and stability of cargo-free NPs were studied with a scanning electron microscope (SEM) and laser particle analyzer. The in vitro radioprotection activity of CUR-loaded NPs was performed. FTIR, Raman, and 1H NMR spectra confirmed that poloxamer188-b-PCL was obtained. TGA curves suggested poloxamer188-b-PCL had better thermo-stability than original poloxamer188. Cell tests suggested that the cargo-free NPs had no cytotoxicity. SEM image showed that the cargo-free NPs were spherical with a diameter of 100 nm. Free radical scavenging experiments proved that CUR-loaded NPs had better antioxidant activity than CUR solutions. CUR-loaded NPs could be detected in all tissues, including liver, kidneys and lung. In summary, this work demonstrated a feasibility of developing an injective formulation of CUR and provided a protection agent in caner radiotherapy.
研究领域:
药学
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生物医学工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2017
·Vol. 8
·期 1
·1-14
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IF 4.211
Xue Xiao-Lei,Han Xiao-Dan,Li Yuan,Chu Xiao-Fei,Miao Wei-Min,Zhang Jun-Ling,Fan Sai-Jun
Background The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated.Methods Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities.Results Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins.Conclusion sThis study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression.
研究领域:
放射生物学
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药理学
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血液学
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DOI
PubMed
高影响因子
LIFE SCIENCES
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2020
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IF 3.647
Meifang Wang,Yinping Dong,Jing Wu,Hongyan Li,Yuanyang Zhang,Saijun Fan,Deguan Li
Aims Ionizing radiation (IR) induces injuries to the hematopoietic and intestinal systems, which are the leading cause of death. Baicalein, a plant-derived flavonoid, shows anti-oxidative stress, anti-apoptosis, anti-inflammation effects in many diseases. In this study, we evaluated the effects and mechanism of baicalein on IR induced intestinal and hematopoietic injuries. Main methods Mice were divided into three groups: Control, IR and IR + Baicalein. All of mice were intraperitoneally administered with 100 mg/kg baicalein or normal saline for 1 h before IR, and then a day post-IR. The changes in intestinal structure, function and molecular expression were observed by pathological experiments and western blot. 16S rRNA gene sequencing was performed to analyze gut microbiota and further predicted metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hematopoietic function was evaluated by peripheral blood cells count and by flow cytometry analysis of hematopoietic cells composition. Key findings Baicalein improved intestinal structure and the ability of proliferation and regeneration after mice exposed to IR, in which the rebalance of gut microbial composition played an important role. KEGG results showed that p53-related apoptotic pathways played important roles in the composition changes of gut microbiota. Then we observed that baicalein inhibited the activation of p53 and p53 mediated mitochondrial apoptosis and death receptor apoptosis in the intestine. In addition, IR induced injuries to hematopoietic system also could be ameliorated by baicalein. Significance These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.
研究领域:
药理学
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放射生物学
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免疫学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
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2024
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IF 8.6
Lu Ganghua,Gao Dingwei,Jiang Wen,Yu Xiaqing,Tong Junyu,Liu Xiaoyan,Qiao Tingting,Wang Ru,Zhang Mengyu,Wang Shaoping,Yang Jianshe,Li Dan,Lv Zhongwei
Background Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131 I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131 I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. Methods A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131 I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. Results 131 I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131 I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. Conclusion These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.
研究领域:
肿瘤学
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胃肠病学
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放射生物学
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微生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Feng-Ling Tang,Li-Wei Xie,Lin-Feng Tang,Hai-Yan Lu,Rui-Qiu Zhu,Di-Fan Wang,Ye Tian,Shang Cai,Ming Li
The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5 + intestinal stem cells (ISCs) and Ki67 + progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis , suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.
研究领域:
放射生物学
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药理学
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分子生物学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2020
·
IF 10.317
Jiani Xie,Chengyan Wang,Ning Wang,Shuang Zhu,Linqiang Mei,Xiao Zhang,Yuan Yong,Lele Li,Chunying Chen,Changshui Huang,Zhanjun Gu,Yuliang Li,Yuliang Zhao
X-ray irradiation-induced toxicity to gastrointestinal tract become a significant clinical problem when using radiotherapy for treating abdominal tumors neighbored to gastrointestinal tissue, which not only often prevents these tumors from receiving a definitive therapeutic dose but also causes a series of gastrointestinal diseases, such as anorexia, abdominal pain, diarrhea and hematochezia. And thus it seriously reduces the therapeutic outcome and life quality of patients. Therefore, the development of gastrointestinal radioprotectors is essential. However, the commercial gastrointestinal radioprotectors in clinical are still rare. In view of this, we prepared bovine serum albumin (BSA) modified graphdiyne (GDY) nanoparticles (GDY-BSA NPs) and for the first time studied its gastrointestinal radioprotection ability. The unique advantages of GDY nanomaterial , including high free radical scavenging ability, good chemical stability in gastric acid condition, relatively longer residence time in gastrointestinal tract and good biosafety under oral administration, provide the favorable prerequisites for it to be used as the gastrointestinal radioprotector. In vitro experimental results indicated that the GDY-BSA NPs powerfully reduced DNA damage and improved viability of the irradiated gastrointestinal cells. In vivo results showed that the GDY-BSA NPs significantly decrease radiation-induced diarrhea, weight loss, and gastrointestinal tissue pathological damage of mice. Furthermore, we also deeply studied the gastrointestinal radioprotective mechanism of GDY-BSA NPs, which indicated that the GDY-BSA NPs effectively inhibited reactive oxygen species (ROS)-induced apoptosis signal pathway, and thus reduced gastrointestinal cell apoptosis. Our work for the first time employed BSA-GDY NPs to mitigating radiation-induced gastrointestinal tract damage, which not only promotes the exploration of new gastrointestinal tract radioprotectors, but also is the good guidance for the treatment of gastrointestinal diseases by nano-drug.
研究领域:
纳米技术
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放射生物学
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药学
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医学研究
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2023
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IF 29.4
Dingxin Liu,Fei Cao,Zhifeng Xu,Chunhua Zhao,Zekun Liu,Jiadong Pang,Ze-Xian Liu,Mahdieh Moghiseh,Anthony Butler,Shaoxia Liang,Weijun Fan,Jiang Yang
Radioprotective agents hold clinical promises to counteract off-target adverse effects of radiation and benefit radiotherapeutic outcomes, yet the inability to control drug transport in human organs poses a leading limitation. Based upon a validated rank-based multigene signature model, we evaluate radiosensitivity indices of diverse normal organs as a genomic predictor of radiation susceptibility. We rationally design S elective OR gan- T argeting (SORT) hafnium oxide nanoparticles (HfO 2 NPs) via modulated synthesis by α-lactalbumin, homing to top vulnerable organs. HfO 2 NPs like Hensify are commonly radioenhancers, but SORT HfO 2 NPs exhibit surprising radioprotective effects dictated by unfolded ligands and Hf(0)/Hf(IV) redox couples. Still, the X-ray attenuation patterns allow radiological confirmation in target organs by dual-beam spectral computed tomography. SORT HfO 2 NPs present potent antioxidant activities, catalytically scavenge reactive oxygen species, and mimic multienzyme catalytic activities. Consequently, SORT NPs rescue radiation-induced DNA damage in mouse and rabbit models and provide survival benefits upon lethal exposures. In addition to inhibiting radiation-induced mitochondrial apoptosis, SORT NPs impede DNA damage and inflammation by attenuating activated FoxO, Hippo, TNF, and MAPK interactive cascades. We propose a universal methodology to reverse radioenhancers into radioprotectors. SORT radioprotective agents with image guidance are envisioned as compelling in personalized shielding from radiation deposition. This article is protected by copyright. All rights reserved
研究领域:
辐射生物学
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纳米技术
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医学成像
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分子生物学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）