Advanced Healthcare Materials
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2025
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IF 9.6
Hai-Dong Qian,Xiang-Yuan Song,Guan-Wen He,Xue-Ni Peng,Ying Chen,Pan Huang,Jing Zhang,Xiao-Yan Lin,Qiao Gao,Sen-Miao Zhu,Tong Li,Zai-Long Chi
Retinal ganglion cell (RGC) degeneration leads to irreversible blindness. Müller glia (MG) play pivotal roles in retinal homeostasis and disease through paracrine signaling. Small extracellular vesicles (sEVs) are bioactive nanomaterials derived from all types of live cells and are recognized as a potential strategy for neuroprotective therapy. The aim of this study is to investigate the potential roles of MG-derived sEVs (MG-sEVs) in a mouse model of optic nerve injury (ONC). It is found that MG-sEVs treatment effectively mitigates RGC degeneration and suppresses microglial activation, thereby improves visual function in ONC mice. Retinal transcriptomic analysis reveals a strong correlation between C-x3-c motif chemokine ligand 1 (Cx3cl1)-mediated glial activation and inflammation. Subsequently, it is confirmed that the expression levels of Cx3cl1 and proinflammatory cytokines are significantly decreased in retinas treated with MG-sEVs. The components analysis of MG-sEVs cargo identifies that miR-125b-5p and miR-16-5p target Cx3cl1 gene to regulate its expression. It is also observed that Cx3cl1 colocalizes on the microglia of transgenic C-x3-c motif chemokine receptor 1 (Cx3Cr1)-GFP mice. In conclusion, MG-sEVs mitigate RGC degeneration by suppressing microglial activation via Cx3cl1-Cx3cr1 signaling. This research provides additional opportunities for the treatment of RGC degeneration.
研究领域:
神经科学
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眼科学
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分子生物学
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DOI
PubMed
高影响因子
INFLAMMATION RESEARCH
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2025
·Vol. 74
·期 1
·1-14
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IF 5.4
Zhang Yan,Yan Xin,Fu Xiao-lei,Yang Hai-bing,Yan Yi-min,He He-fan,Yang Li
Background Clinical studies have demonstrated that multiple inflammatory related proteins are associated with hypertrophic cardiomyopathy (HCM). However, the precise role of these factors in the pathogenesis of HCM remains uncertain. Methods The link between inflammatory related proteins and HCM was analyzed using Mendelian randomization (MR), followed by bioinformatics to explore the role of inflammatory related proteins in HCM. In vivo and in vitro models of HCM were established to elucidate how inflammatory related proteins influence HCM progression. Results Our MR analysis revealed a negative correlation between the inflammation related protein CX3CL1 and HCM. Bioinformatics and in vivo data similarly demonstrated a reduction in CX3CL1 expression in HCM. CX3CL1 was found to be mainly expressed in cardiomyocytes and endothelial cells via the Human Protein Atlas database and its’ expression in both cells was obviously downregulated after being treated by angiotensin-II. Importantly, functional characteristics and correlation analysis of CX3CL1 indicated that it was most closely associated with macrophages efferocytosis. Consequently, we examined the signature molecules (AXL, MERTK, and TYRO3) associated with efferocytosis, which revealed a significant decrease in their expression in HCM. Notably, recombinant mouse CX3CL1 (rm-CX3CL1) reversed this process. Conclusions In conclusion, CX3CL1-meidated impaired efferocytosis plays a critical role in the initiation and development of HCM, and modulation of CX3CL1 may prove advantageous in managing HCM progression.
研究领域:
心脏病学
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分子生物学
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免疫学
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基因组学
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病理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Yulin Qi,Lu Liu,Dan Liang,Shiyun Tang,Xiaoyi Yu,Hejiang Ye,Nianzhi Chen
Background Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases . The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine , has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. Purpose Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N -Methyl- N -Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. Methods To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL , retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot , real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. Results Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1β, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK . Conclusion In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.
研究领域:
眼科学
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药理学
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神经科学
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中医
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
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2021
·Vol. 83
·期 2
·328-338
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IF 4.36
Min Wu,Mengmeng Jin,Xiaohui Cao,Kun Qian,Lei Zhao
Adenosine deaminases acting on RNA 1 (ADAR1) has been identified to play key roles in non-small cell lung cancer (NSCLC) progression, and can modulate the sensitivity of cancer cells to anticancer drugs. The current study aimed to investigate the effect of ADAR1 on the sensitivity of NSCLC cells to anlotinib. We established anlotinib-resistant NSCLC (NSCLC/AR) cells, including NCI-H1975/AR and A549/AR cells. Results showed that ADAR1 was significantly upregulated in NSCLC/AR cells. Genetic-knockdown of ADAR1 increased the sensitivity of NSCLC/AR cells to anlotinib by inducing cell proliferation suppression, cell cycle arrest, and apoptosis. Furthermore, knockdown of ADAR1 decreased the level of C-X3-C motif chemokine ligand 1 (CX3CL1) in NCI-H1975/AR and A549/AR cells after anlotinib treatment. Introduction of exogenous CX3CL1 significantly reversed the positive effect of ADAR1 deficiency on NSCLC/AR cell sensitivity, exhibited by the increase of cell viability and decrease of apoptosis. Further in-vivo study demonstrated that knockdown of ADAR1 inhibited NCI-H1975/AR cell tumorigenesis by reducing CX3CL1 expression. Collectively, ADAR1 deficiency increased the sensitivity of NSCLC/AR cells to anlotinib by downregulating CX3CL1, which might provide a potential strategy for NSCLC/AR therapy.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
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2023
·Vol. 20
·期 1
·1-16
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IF 9.3
Long Dan-dan,Zhang Yu-zhuo,Liu An,Shen Liang,Wei Hong-rui,Lou Qian-qian,Hu Shan-shan,Chen Dan-yang,Chai Xiao-qing,Wang Di
Background Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice.Methods We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons.Results Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells.Conclusion Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.
研究领域:
神经科学
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疼痛研究
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药理学
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产品关联
DOI
PubMed
高影响因子
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