CURRENT NEUROVASCULAR RESEARCH
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2022
·Vol. 19
·期 1
·61-72
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IF 2.294
Xu Shu-Ying,Zeng Chun-Li,Ni Si-Ming,Peng Yong-Jun
Background: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote
angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral
stroke via exosome-carried miR-210. Methods: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume
of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). Results: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment
significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions
compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. Conclusion: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal
miR-210.
研究领域:
神经科学
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分子生物学
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中医药学
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中风研究
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Zhi-Li Yao,Qing-Nan Li,Yong-Ji Li,Hao-Rui Li,Si-Wei Yang,Chen-Yu Wang,Jia-Yi Shi,Shun-Li Wu,Shuang-Qing Liu,Gui-Mei Han,Jing Wang,Li-Yong Xing,Yan Zhao,De-Ming Kong,Qi-Liang Cai
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer in adults, with rising global incidence and mortality rates. Early diagnosis is critical for improving patient outcomes. However, current diagnostic techniques often rely on expensive and complex instrumentation, which limits their accessibility. This creates an urgent need for affordable, sensitive, and user-friendly diagnostic methods. MiR-210–3p, a biomarker significantly upregulated in ccRCC, shows promise for non-invasive diagnostic applications. In this study, we innovatively developed a fluorescence-colorimetric dual-mode platform for miR-210–3p detection by utilizing a recently identified hemin aptamer with a stem-loop structure and by combining the trans -cleavage activity of the CRISPR/Cas12a system with the peroxidase-like activity of the aptamer/hemin complex. Moreover, using fluorescently labeled aptamer or its complementary sequence as cleavage substrates for CRISPR/Cas12a allows us to achieve two types of dual-mode detection: fluorescence “turn on” combined with colorimetric “turn off”, and fluorescence “turn on” combined with colorimetric “turn on”. This dual-mode detection platform combines sensitive quantification (with a detection limit for miR-210-3p of 0.95 pM) with rapid and visually interpretable on-site analysis, significantly enhancing the reliability and accuracy of test results. The platform has good scalability, as it is capable of detecting miR-210-3p and can also be extended to detect other tumor biomarkers. This versatility holds great potential for integration with big data analytics to personalize miRNA profiles, aiding in tumor staging, monitoring, and the development of treatment strategies, thereby advancing the field of precision medicine.
研究领域:
分子生物学
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肿瘤学
·
诊断学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Yao Guo,Jing Cui,Xueyi Liang,Taoyu Chen,Chong Lu,Tao Peng
Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Xu Jie,Zhuang Xiuxiu,Wu Zichang,Yan Fuyi,Shi Deen,Ye Fan,Ding Ruihua,Gao Qi,Yao Qimin,Liu Yiying,Dong Xiaoyu,Zhang Fan,Li Binbiao,Xu Xiangwei,Tong Hongfei,Yao Yanzhi,Jiang Wenbing,Xiao Jian,Li Zhenglin,Chen Wei
Ischemic skin flaps are highly susceptible to distal necrosis because of insufficient perfusion, oxidative stress, and dysregulated cell death. Here, we investigated the role of Hippo/YAP signaling in ischemic flap survival and identified its upstream regulatory mechanism. Hippo pathway inactivation, characterized by reduced MST1/2 and LATS1/2 phosphorylation and enhanced YAP nuclear localization, was preferentially associated with viable flap regions. Mechanistically, ischemia-induced HIF-1α upregulated miR-210-3p, which suppressed ephrin-A3 (EFNA3), weakened the EFNA3–YAP interaction, and promoted YAP nuclear translocation. Re-expression of EFNA3 partially reversed miR-210-3p-induced YAP activation and cytoprotection, confirming its functional involvement. Mechanistically, ischemia-induced HIF-1α increased miR-210-3p expression, which suppressed EFNA3 and facilitated YAP nuclear localization. EFNA3 re-expression partially reversed miR-210-3p-induced YAP activation, supporting its functional involvement. MiR-210-3p treatment was further associated with reduced oxidative injury, lipid peroxidation, mitochondrial dysfunction, and ferroptosis-related molecular alterations, together with improved perfusion and flap survival. In vivo, miR-210-3p improved local perfusion and flap survival. We further developed a virus-inspired biomimetic nanoparticle for miR-210-3p delivery, which achieved protective effects comparable to AAV-mediated delivery in vitro and in vivo. These findings identify the miR-210-3p–EFNA3–YAP axis as an important regulator of ischemic tissue adaptation and provide a non-viral miRNA delivery strategy for ischemic flap repair.
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高影响因子
Materials Horizons
·
2025
·
IF 10.7
Linlin Zhao,Meiyu Hu,Xiaohang Yin,Hao Yang,Liyun Zhu,Pingyuan Sun,Xiya Wang,Songwei Ai,Yonghui Zheng,Genjie Li,Tingting Yang,Xuerui Chen,Jingyu Zhang
Effectively alleviating cerebral ischemia-reperfusion (I/R) injury is challenging despite medical advances. Prompt restoration of blood flow after ischemic stroke causes secondary damage to brain tissue, triggers neuroinflammation and overproduces reactive oxygen species (ROS). MiRNA regulates genes involved in neuron apoptosis and neuroinflammation, thus exhibiting potential in ameliorating cerebral I/R injury. However, as miRNA is vulnerable to degradation, its effective delivery poses obstacles to clinical applications. Inspired by therapeutic potential of miR-210 inhibitors in ischemic stroke-induced neuroinflammation, we constructed a multifunctional nanosystem composed of ceria nanozymes and zeolitic imidazolate framework-90 (ZIF-90) nanoparticles to deliver miR-210 inhibitors to treat cerebral I/R injury. Attributed to proton sponge effect of ZIF-90, this nanosystem allows for lysosome escape of miR-210 inhibitors to protect their intracellular bioactivity, while integration of ZIF-90 and ceria nanozymes utilizes multi-enzyme cascade activities to constrain lipid peroxidation and reduce oxidative damage in brain tissues of mice with middle cerebral artery occlusion (MCAO). After crossing the blood-brain barrier, miR-210 inhibitors target TET2 to suppress pro-inflammatory cytokines, finally inhibiting neuroinflammation. More than uncertain stability and efficacy of direct TET2 protein administration, delivery of miR-210 inhibitors by multifunctional nanosystems engendered neuroprotection, indicating their potential for protein replacement therapy against cerebral I/R injury.
研究领域:
神经科学
·
纳米技术
·
分子生物学
·
药剂学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
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