IN VIVO
·
2024
·Vol. 38
·期 3
·1133-1142
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IF 1.8
LONGJIE XU,LILI HOU,CHUN CAO,XIAOHUA LI
Background/Aim: Cancer-induced bone pain (CIBP) is one of the most common symptoms of bone metastasis of tumor cells. The hypothalamus may play a pivotal role in the regulation of CIBP. However, little is known about the exact mechanisms. Materials and Methods: First, we established a CIBP model to explore the relationship among hypothalamic ghrelin, NPY and CIBP. Then, we exogenously administered NPY and NPY receptor antagonists to investigate whether hypothalamic NPY exerted an antinociceptive effect through binding to NPY receptors. Finally, we exogenously administered ghrelin to investigate whether ghrelin alleviated CIBP by inducing the production of hypothalamic NPY through the AMPK-mTOR pathway. Body weight, food intake and behavioral indicators of CIBP were measured every 3 days. Hypothalamic ghrelin, NPY and the AMPK-mTOR pathway were also measured. Results: The expression of hypothalamic ghrelin and NPY was simultaneously decreased in cancer-bearing rats, which was accompanied by CIBP. Intracerebroventricular (i.c.v.) administration of NPY significantly alleviated CIBP in the short term. The antinociceptive effect of NPY was reversed with the i.c.v. administration of the Y1R and Y2R antagonists. The administration of ghrelin activated the AMPK-mTOR pathway and induced hypothalamic NPY production to alleviate CIBP. This effect of ghrelin on NPY and antinociception was reversed with the administration of a GHS-R1α antagonist. Conclusion: Ghrelin could induce the production of hypothalamic NPY through the AMPK-mTOR pathway to alleviate CIBP, which can provide a novel therapeutic mechanism for CIBP.
研究领域:
神经科学
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疼痛研究
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肿瘤学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 31
·6837-6844
·
IF 5.344
Xuechen Qian,Yinjie Wang,Youfeng Xu,Ling Ma,Nianyu Xue,Zhenqi Jiang,Yi Cao,Ozioma Udochukwu Akakuru,Juan Li,Shengmin Zhang,Aiguo Wu
Ultrasound cavitation therapy has attracted much attention in recent years because the cavitation of microbubbles can be leveraged to boost the infiltration of chemotherapeutic drugs into cancer tissues. For breast cancer therapy, most of the previously reported microbubbles lack specific targeting capacity and permeability. In this study, we have successfully fabricated Y1 receptor ligand (NPY)-modified bubbles, and examined their therapeutic efficacies as size-dependent functions with or without NPY targeting. To achieve this, four types of micro-scale bubbles (MBs or MBs-NPY) and nano-scale bubbles (NBs or NBs-NPY) were comprehensively evaluated. In vivo results indicated that the NBs-NPY group with doxorubicin (DOX) under ultrasound irradiation showed a high tumor suppression effect and a prolonged survival time. Furthermore, the NBs-NPY with DOX group exhibited minimal damage to mouse vital organs, which points to the considerable tolerance of the proposed nanosystem for efficacious breast cancer therapy. In summary, these findings suggest that the developed NPY-targeted NBs could have a broad application prospect in ultrasound cavitation chemotherapy of Y1 receptor-overexpressed breast cancer.
研究领域:
肿瘤学
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治疗学
·
纳米技术
·
超声工程
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2023
·Vol. 16
·期 12
·1642
·
IF 4.6
Yuan He,Ziyang Li,Huiling Su,Yanan Sun,Wei Shi,Yunfeng Yi,Dongtao Ge,Zhongxiong Fan
Polydopamine (PDA) as a melanin-like biomimetic material with excellent biocompatibility, full spectrum light absorption capacity and antioxidation property has been extensively applied in the biomedical field. Based on the high reactivity of dopamine (DA), exploiting new strategies to fabricate novel PDA-based nano-biomaterials with controllable size and improved performance is valuable and desirable. Herein, we reported a facile way to synthesize pyrrole-doped polydopamine-pyrrole nanoparticles (PDA-nPY NPs) with tunable size and enhanced near-infrared (NIR) absorption capacity through self-oxidative polymerization of DA with PY in an alkaline ethanol/H2O/NH4OH solution. The PDA-nPY NPs maintain excellent biocompatibility and surface reactivity as PDA. By regulating the volume of added PY, PDA-150PY NPs with a smaller size (<100 nm) and four-fold higher absorption intensity at 808 nm than that of PDA can be successfully fabricated. In vitro and in vivo experiments effectively further demonstrate that PDA-150PY NPs can effectively inhibit tumor growth and completely thermally ablate a tumor. It is believed that these PY doped PDA-nPY NPs can be a potential photothermal (PT) agent in biomedical application.Keywords:polydopamine;pyrrole;self-oxidative polymerization;photothermal treatment;cancer therapy
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Juan Li,Zheyu Shen,Xuehua Ma,Wenzhi Ren,Lingchao Xiang,An Gong,Tian Xia,Junming Guo,Aiguo Wu
By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.
研究领域:
癌症研究
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纳米技术
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药学科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Xuejun Yuan,Wenjie Chen,Rui Li,Huijun Guo,Chunyang Wang
Deoxynivalenol (DON) is one of the most prevalent mycotoxins and can induce weight loss and vomiting in animals. This study aimed to elucidate the molecular mechanisms underlying DON-induced anorexia in rabbits through the microbial-gut-brain axis. A total of forty rabbits were randomly divided into a DON group and a control group, receiving 1.5 mg/kg.BW of DON and an equivalent volume of saline daily via intragastric administration, respectively. The pre-treatment period lasted for 7 days, followed by a formal experimental period of 24 days. The findings revealed that DON exposure significantly reduced daily food intake and weight gain, leading to intestinal apoptosis and barrier injuries. 16S rRNA sequencing data indicated that DON exposure decreased the diversity and richness of cecal microflora, suppressed probiotic populations, and disrupted host lipid metabolism. RNA-Seq and iTRAQ data were used to cross-analyze the shared differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in the hypothalamus and jejunum, along with their shared enrichment pathways, indicating that TNF-α, NF-κB, and NPY may play pivotal roles in DON-induced anorexia. qRT-PCR and Western blotting results confirmed significant increases in mRNA and protein expression levels of TNF-α, NF-κB and 5-HT2A in both the hypothalamus and jejunum. In conclusion, DON ingestion in rabbits can disrupt the intestinal barrier, up-regulate the expression of IFN-γ, TNF-α, NF-κB, and 5-HT2A in the intestine, and trigger an immuno-inflammatory response in the hypothalamus via the microbial-gut-brain axis, ultimately resulting in appetite suppression and weight loss.
研究领域:
毒理学
·
分子生物学
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微生物学
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动物科学
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营养学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 14
·6452-6463
·
IF 5.396
Li Meng,Yuehua Jiao,Xiaohong Zhou,Cong Liang,Kexin Yan,Ye Zhao,Xiujie Deng,Xue Han,Yanyan Yang,Hanmin Liu,Pimin Gong,Lanwei Zhang
Despite the health benefits of Vitis vinifera L. leaves, its anti-obesity potential has not been fully explored. In this work, we showed that Vitis vinifera L. leaf extract (VLE) inhibits the pancreatic lipase activity. Intragastric administration of VLE to mice led to a significant decrease in the body weight, tissue fat accumulation, levels of cholesterol, low-density lipoprotein and triglyceride compared to mice fed with high fat diet. We also found a lower level of neuropeptide-Y (NPY) in the serum and hypothalamus and a higher level of fibroblast growth factor 15 in mice supplemented with VLE. These results suggested that VLE regulates both the NPY-mediated pathway and the bile acid-FGF15 pathway to control energy metabolism and body weight gain. The composition of VLE was further investigated by a targeted metabolomics approach, which identified 21 compounds including phenolic acids, flavones, flavanols, flavanones, coumarins, and stilbenes. Taken together, we demonstrated the capacity of grape leaves in reducing obesity, which could be mediated by NPY and bile acids. Identification of putative active compounds in VLE also open the path for further studies to determine their effectiveness individually to treat obesity.
研究领域:
营养学
·
药理学
·
分子生物学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
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