JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Penghao Zhen,Qiaochu Jiang,Fuchao Yu,Xuan Xu,Qin Wei,Xiaoyang Liu,Xianbao Sun,Gaolin Liang,Jiayi Tong
Treatment of myocardial ischemia-reperfusion (MI/R) injury still faces the lack of clinically approved drugs. Apelin-13 is a highly promising drug candidate of MI/R injury, but hampered by its extremely short half-life in plasma. This calls for efficient and smart delivering system for Apelin-13 delivery, but has not been reported. Herein, a reactive oxygen species (ROS)-responsive hydrogelator YFF-TK-FFY is designed, which co-assembles with Apelin-13 to form the peptide hydrogel Apelin-13@Gel TK . This hydrogel responds to ROS at varying levels in the surrounding environment of MI/R and releases Apelin-13 at different rates. In an MI/R injury mouse model, Apelin-13@Gel TK rapidly releases Apelin-13 in response to the high ROS in the core area of MI/R injury, efficiently reducing cardiomyocyte apoptosis within three days. In the ROS-low border zone, Apelin-13@Gel TK provides a slow and sustained release of Apelin-13, promoting angiogenesis and lymphatic remodeling, and facilitating the resolution of inflammation in the later repair stage after MI/R injury. By offering a spatiotemporally controlled drug release in response to ROS gradients in the MI/R microenvironment, this smart hydrogel presents a promising therapeutic strategy for effective treatment of MI/R injury.
研究领域:
药理学
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心血管病学
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生物材料科学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2022
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IF 3.197
Sheng Hu,Pei Shen,Bin Chen,Shao-Wen Tian,Yong You
Neuroinflammation is usually associated with cognitive decline, which is involved in neurodegenerative diseases. Apelin , a neuropeptide, exerts various biological roles in central nervous system. Recent evidence showed that apelin-13, an active form of apelin, suppresses neuroinflammation and improves cognitive decline in diverse pathological processes. However, the underlying mechanism of apelin-13 in neuroinflammation remains largely unknown. The present study aimed to determine underlying mechanism of apelin-13 on neuroinflammation-related cognitive decline. The lipopolysaccharide (LPS) intracerebroventricular (i.c.v.) to is used to establish a rat model of neuroinflammation-related cognitive decline. The results showed that apelin-13 inhibits LPS-induced neuroinflammation and improves cognitive impairment. Apelin-13 upregulates the GR level and nuclear translocation in hippocampus of rats. Moreover, glucocorticoid receptor inhibitor RU486 prevents apelin-13-mediated neuroprotective actions on cognitive function. Taken together, apelin-13 could exert a protective effect in neuroinflammation-mediated cognitive impairment via the activation of GR expression and nuclear translocation.
研究领域:
神经科学
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药理学
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神经炎症
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认知功能
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang
Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
研究领域:
骨生物学
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内分泌代谢病学
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分子药理学
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细胞信号转导
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氧化应激与抗氧化
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骨骼系统疾病
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转化医学
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DOI
PubMed
高影响因子
Tissue Barriers
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2024
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IF 3.6
Qi Cao,Wei Zeng,Jingmin Nie,Yongjun Ye,Yanchao Chen
Impairment of the blood – brain barrier (BBB) and subsequent inflammatory responses contribute to the development of human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND). Apelin-13, the most abundant member of the apelin family, acts as the ligand of the angiotensin receptor-like 1 (APJ). However, its pharmacological function in HAND and its underlying mechanism are unknown. In the current study, we report that the presence of HIV-1 Tat reduced the levels of Apelin-13 and APJ in the cortex tissue of mice. Importantly, Apelin-13 preserved BBB integrity against HIV-1 Tat in mice by increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludin. Interestingly, increased macrophage infiltration, indicated by elevated CD68-positive staining was observed in the cortex after stimulation with HIV-1, which was mitigated by the administration of Apelin-13. Correspondingly, Apelin-13 reduced the expression of monocyte chemoattractant protein-1; (MCP-1). An in vitro two-chamber and two-cell trans-well assay demonstrated that HIV-1 Tat challenge significantly promoted macrophage migration, which was notably attenuated by the introduction of Apelin-13. Accordingly, treatment with Apelin-13 restored the HIV-1 Tat-induced reduction of occludin and ZO-1, while preventing the upregulation of MCP-1 in human brain microvascular endothelial cells (HBMVECs). Our results suggest that Apelin-13 may reduce macrophage infiltration into brain tissues and mitigate BBB dysfunction in patients with HAND.
研究领域:
神经科学
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免疫学
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药理学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
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2016
·Vol. 41
·期 7
·1635-1644
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IF 2.472
Zou Yunjun,Wang Bo,Fu Wan,Zhou Shouhong,Nie Yaxiong,Tian Shaowen
It is widely accepted that environmental stress is a risk factor for mental disorders. Glucocorticoid hormones play a vital role in the regulation of physiological response to stress. High concentrations of corticosterone can induce cellular damage in PC12 cells, which possess typical neuronal features. Apelin and its receptor APJ are widely distributed in the central nervous system including limbic structures involved in stress responses. Previous studies have suggested that apelin has a neuroprotective function. However, the effect of apelin on corticosterone-induced neuronal damage remains to be elucidated. In the present study, we explored the potential protective activity of apelin-13 in PC12 cells treated with corticosterone and its underling mechanisms. The viability of the cells, the apoptosis of the cells, the level of phosphorylation of Akt (p-Akt) and extracellular signal-regulated kinases (p-ERKs) and cleaved caspase-3 expression were detected by MTT, Hoechst staining and flow cytometer assays and Western blotting. Results showed that corticosterone induced cells viability loss, cell apoptosis, down-regulation of p-Akt and p-ERKs and up-regulation of cleaved caspase-3. The effects induced by corticosterone were attenuated by apelin-13 pretreatment. Furthermore, apelin-13-mediated anti-viability loss, antiapoptosis and caspase-3 suppression activities were blocked by specific inhibitors of phosphatidylinositol 3-kinase (PI3K) (LY294002) and ERKs (PD98059). The data suggest that apelin-13 protects PC12 cells from corticosterone-induced apoptosis through activating PI3K/Akt and ERKs signaling pathways.
研究领域:
神经科学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
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