JOURNAL OF NANOBIOTECHNOLOGY
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2025
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IF 12.6
Zhe Zhang,Guangyu Jia,Qi Wang,Yamei Yu,Xiaolong Tang,Heqing Zheng,Xinyu Yang,Yao Xiao,Yangrui Ou,Jingjing Jiang,Hua Guo,Ye Wang,Shiyong Li
Intranasal drug delivery via nanocarriers has long been a research focus for enhancing drug concentration in the brain. However, the strategy of exploiting blood–brain barrier (BBB) alterations in atherosclerotic mouse models to enhance nanoparticle-mediated delivery of bromocriptine to the hypothalamus for the treatment of prolactinomas with hyperprolactinemia has not yet been reported. This study reveals that in patients with prolactinomas complicated by arteriosclerosis, bromocriptine therapy more effectively attenuates postoperative elevations in prolactin levels. In a mouse model, liposome-encapsulated bromocriptine efficiently traversed the nasal mucosa and entered the intracranial space. Compared with normal mice, bromocriptine-loaded liposomes delivered higher bromocriptine concentrations to the hypothalamus. Single-cell RNA sequencing revealed a significant upregulation of organic anion-transporting polypeptide 1a4 (Oatp1a4) expression in the brain endothelial cells of atherosclerotic mice. Importantly, bromocriptine-loaded liposomes more effectively reduced prolactin levels in a mouse model of prolactinoma with concurrent atherosclerosis. This study provides a theoretical foundation for the precision treatment of prolactinomas in arteriosclerosis.
研究领域:
药理学
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神经科学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL SCIENCE
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2024
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IF 2.7
Ma Zifeng,Li Qiao,Xu Hongmei,Li Yueyue,Wang Shujin,Xiong Yan,Lan Daoliang,Li Jian,Xiong Xianrong,Fu Wei
Zearalenone (ZEN), a mycotoxin from Fusarium fungi, impairs fertility and milk production in female animals, however, the mechanisms remain poorly understood. Using the bovine mammary epithelial cells (MAC-T) as the model, this study investigated the impacts of ZEN on programmed cell death (PCD) and milk fat synthesis, and explored the underlying mechanism. We found that 10 ng/mL prolactin (PRL) notably enhanced the differentiation of MAC-T cells, promoting the expression of genes related to the synthesis of milk fat, protein, and lactose. Next, the toxic effects of different doses of ZEN on the differentiated MAC-T with PRL treatment were determined. 10 μM and 20 μM ZEN significantly reduced cell viability, induced oxidative stress, and triggered PCD (e.g. apoptosis and necrosis). Notably, ZEN exposure downregulated the mRNA/protein levels of critical factors involving in milk fat synthesis by disrupting the AKT-mTOR-PPARγ-ACSL4 pathway. Interestingly, melatonin (MT), known for its antioxidant properties, protected against the above ZEN-induced effects by enhancing the binding of PPARγ to the promoter regions of ACSL4, which led to the upregulated expression of ACSL4 gene. These results underscored the potential of MT to mitigate the adverse effects of ZEN on mammary cells, highlighting a way for potential therapeutic intervention.
研究领域:
兽医学
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毒理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
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2024
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IF 3.9
Yuqing Zhang,Wenying Zhang,Yanmin Jian,Shujing Zhang,Dongwu Liu,Kang Zheng,Xungang Tan,Feng You,Qiuxiang Pang,Shuang Jiao
Olive flounder ( Paralichthys olivaceus ) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 ( fzd3 ) and prolactin ( prl ) in brains/pituitaries, and growth hormone receptor ( ghr ), estrogen receptor ( esr1 ), insulin-like growth factor binding protein-3 ( igfbp3 ), bone morphogenetic protein 8A-like ( bmp8a ), leptin receptor ( lepr ), and lipoprotein lipase-like ( lpl ) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.
研究领域:
海洋生物学
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基因组学
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转录组学
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内分泌学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）