BRAIN RESEARCH
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2025
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IF 2.6
Naizhu Wang,Jingkun Wu,Zhaofei Song,Hongbin Wang,Yan Zhao
Hypertension in the brain may lead to hypertensive intracerebral hemorrhage (HICH), a devastating disease. This study, grounded on bioinformatics insights, aims to investigate the functions of Selectin E (SELE) and forkhead box P1 (FOXP1) in the progression of HICH. Increased SELE expression was detected in the striatum of a mouse model of HICH generated via angiotensin II and L-NAME treatments. Knockdown of SELE alleviated hemorrhage, neutrophil infiltration, and blood–brain barrier (BBB) rupture in the mouse brain. FOXP1, poorly expressed in the HICH mice, was found to repress SELE transcription by binding to its promoter region. Overexpression of FOXP1 resulted in analogous alleviating effects in the HICH mice; however, the effects were abrogated by the additional SELE overexpression. In vitro , human brain microvascular endothelial cells (HBMECs) were treated with thrombin to generate a cellular model of ICH, followed by co-culture with HL-60 cell-derived neutrophils. The FOXP1 overexpression reduced the adhesion of neutrophils, and it alleviated HBMEC apoptosis and permeability while enhancing angiogenesis. Still, these effects were counteracted by the SELE upregulation. In conclusion, this study demonstrates that SELE upregulation upon FOXP1 loss is associated with neutrophil infiltration and BBB rupture in HICH.
研究领域:
神经病学
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分子生物学
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心血管疾病
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免疫学
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生物信息学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Mingxing Li,Xuwei Shang,Haiya Lou,Zixu Wang,Shanshan Xiang,Yihe Qiu,Fuqiang Hu,Fangying Yu,Hong Yuan
Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site. Briefly, a nitrobenzene group is incorporated into the framework of a nanocarrier, and then it is simultaneously linked with chitosan. Additionally, the surface of the nanocarrier with sialic acid (SA) and encapsulated the clinically used drug ambrisentan (Am), which enables the anchoring of E-selectin and subsequent drug delivery is modifed. This system facilitates intercellular transport to pulmonary artery smooth muscle cells (PASMCs) when targeting PAECs and specifically responds to a reductive hypoxic microenvironment with elevated nitroreductase in PASMCs. Moreover, compared with free Am, nanoencapsulation and SA-PEG 2000 -NH 2 prolong the blood circulation time, achieving better therapeutic outcomes in preventing vascular remodeling and reversing systolic dysfunction. The originality and contribution of this work reveal the promising value of this pulmonary arterial anchoring stimuli-responsive nanocraft as a novel therapeutic strategy for satisfactory PAH treatment.
研究领域:
纳米技术
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药学
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心血管医学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Huafeng Yang,Hui Liu,Yuan Zheng,Bo Li,Shujing Wang,Jun Zhang,Jiandong Wang
Cornus officinalis total glycosides (COTG) derived from the traditional Chinese medicine Cornus officinalis, is a natural immunosuppressant and has been extensively studied in immunomodulation and immunosuppression. This study aimed to explore the effects of COTG on granulomatous lobular mastitis (GLM) and its associated mechanisms. Compared to the model group, COTG effectively ameliorated histopathological damage to breast tissue, reduced mammary gland suppuration, and enhanced the blood-milk barrier. Additionally, COTG treatment reduced the total number of T cells and B cells in GLM rats, significantly improving clinical indicators such as P-selectin, E-selectin, and intercellular cell adhesion molecule-1. We also observed downregulation of CD28 and B7 expression levels, an upregulation of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression, and a significant decrease in inflammatory marker levels in the COTG group. COTG exerts an anti-inflammatory effect in GLM by stimulating CTLA-4, inhibiting the B7-CD28 signaling pathway affecting T cell activation, and promoting the blood-milk barrier. These findings suggest that COTG could be a promising therapeutic option for managing GLM, potentially improving patient outcomes by modulating immune responses and reinforcing the blood-milk barrier.
研究领域:
药理学
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免疫学
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病理学
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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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