Molecular & Cellular Toxicology
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2025
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IF 1.4
He Chaojie,Fan Hongyan,Zhu Chunyan,Huang Yueqing
Background Ischemia–reperfusion (I/R) injury is a severe disorder during revascularization therapy against acute myocardial infarction. Objective Our study aims to investigate the role and regulation mechanism of Annexin A1 (ANXA1) against I/R injury. Results Western blotting analysis showed that ANXA1 expression in rat cardiomyocytes (H9C2 cells) was notably decreased by oxygen–glucose deprivation/reperfusion (OGD/R) treatment. Meanwhile, the NLRP3 inflammasome activation accompanied by pyroptosis and inflammation was observed in H9c2 cells under OGD/R induction. Besides, overexpression or knockdown of ANXA1 dramatically inhibited or aggravated NLRP3-mediated pyroptosis and inflammation. Further investigations found that the m 6 A level of ANXA1 was upregulated by OGD/R, thus leading to decreased mRNA stability in H9C2 cells. FTO, a N6-methyladenosine (m 6 A) “eraser”, was downregulated in H9C2 cells by OGD/R and shown to increase the ANXA1 protein expression by demethylating mRNA in H9c2 cells under OGD/R induction. Moreover, knockdown FTO reversed the protection of ANXA1 against NLRP3-mediated pyroptosis and inflammation in OGD/R-induced H9C2 cells. Conclusion ANXA1 protects cardiomyocytes against I/R injury by alleviating NLRP3-mediated pyroptosis and inflammation via FTO-mediate demethylation. These findings innovatively suggest the therapeutic potential of ANXA1 for myocardial I/R injury.
研究领域:
分子生物学
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心脏病学
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表观遗传学
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产品关联
DOI
高影响因子
Biofabrication
·
2025
·
IF 8
Ruoyu Li,Wenfeng Li,Yungshan Teng,Runze Li,Siyi Kong,Xin Chen,Haotian Luo,Danying Chen,Yuqing Guo,Yangqiao Qing,Hio Cheng leong,Bingyan Guo,Meihan Chen,Zixin Pan,Shushuo Zheng,Yihong Deng,Yang Cao,Chen Zhou,Xuenong Zou,Weicai Wang
Craniofacial bone defect healing in periodontitis patients with diabetes background has long been difficult due to increased blood glucose levels which cause overproduction of reactive oxygen species (ROS) and a low pH environment. These conditions negatively affect the function of macrophages, worsen inflammation and oxidative stress, and ultimately, hinder osteoblasts' bone repair potential. In this study, we for the first time found that ANXA1 expression in macrophages was reduced in a diabetic periodontitis environment, with the activation of the NLRP3/Caspase-1/GSDMD signaling pathway, and, eventually, increased macrophage pyroptosis. Next, we have developed a new GPPG intelligent hydrogel system which was ROS and pH responsive, and loaded with Ac2-26, an ANXA1 bioactive peptide, and osteogenic peptide OGP as well. We found that Ac2-26/OGP/GPPG can effectively reduce ROS, mitigates macrophage pyroptosis via the ANXA1/NLRP3/Caspase-1/GSDMD pathway and enhanced osteogenic differentiation. The effect of Ac2-26/OGP/GPPG in regulation of pyroptosis and bone defect repair was also further validated by animal experiments on periodontitis-induced tooth loss model in diabetic rats. To conclude, our study unveils the effect of ANXA1 on macrophage pyroptosis in periodontitis patients with diabetes, based on which we introduced a promising innovative hydrogel system for improvement of bone defects repair in diabetic periodontitis patients via targeting macrophage pyroptosis and enhancing osteogenic potential.
研究领域:
牙科学
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药理学
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生物医学工程
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免疫学
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
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IF 12.4
Xi Yang,Bolin Li,Wei Li,Zirui Wang,Kexuan Zhao,Zhonghao Hu,Yahan Peng,Tongtong Yang,Chenbing Wang
Impaired macrophage efferocytosis is a major barrier to timely inflammatory resolution in chronic diabetic wounds. We developed an aligned core-shell gelatin/chitosan dressing for local delivery of losmapimod, a p38 MAPK inhibitor, and achieved a controlled, time-decreasing release profile while preserving wet-state structural integrity. In vitro, losmapimod upregulated ANXA1 and enhanced both macrophage efferocytosis and phagocytic activity. In db/db wounds, the losmapimod-loaded scaffold accelerated healing and improved multiple histological features of pro-healing remodeling, including reduced fibrotic signaling, enhanced vascularization, increased epithelial progenitor-associated signals, and more mature collagen organization. Transcriptomic analysis further supported attenuation of inflammatory recruitment-associated programs together with enrichment of epidermal repair-related pathways. Gain- and loss-of-function studies in macrophages, together with in vivo pharmacological modulation, implicated ANXA1-related signaling as an important contributor to these effects. Together, these findings support a local, time-programmed pro-resolution biomaterial strategy for diabetic wound repair and identify macrophage clearance-associated remodeling as a relevant therapeutic axis.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·Vol. 24
·期 1
·822
·
IF 15
Gao Xiaoke,Zhang Meng,Yao Xiaohan,Wang Jing,Wang Xueying,Lou Xiaohan,Wan Jiajia,Duan Xixi,Zhang Lijing,Lei Ningjing,Huang Hefei,Huang Siyuan,Yan Linlin,Qin Bo,Zhang Jinkun,Qin Zhihai,Wang Fazhan
Lung metastasis remains a determinant of poor prognosis and survival in breast cancer and is understood to depend on a permissive pulmonary immune niche rather than tumor cell traits alone. Here, we developed a host-directed RNA interference strategy to modulate this niche by reprogramming pulmonary B cells for breast cancer lung metastasis treatment. IF7C peptide-decorated cationic liposomes were constructed, which preferentially accumulated in the lung, and were internalized by pulmonary B cells, enabling selective silencing of annexin A1 (ANXA1). In tumor-conditioned primary B cells, ANXA1 knockdown reshaped the transcriptional landscape and shifted cytokine output away from an immunosuppressive profile characterized by IL-10, TGF-β, and IL-35. Functionally, ANXA1-silenced B cells lost their capacity to drive CD4⁺ T cells toward Foxp3⁺ regulatory differentiation and instead promoted Th1 features, while concurrently relieving suppression of CD8⁺ T-cell proliferation. In two postoperative syngeneic breast cancer models, perioperative administration achieved ANXA1 silencing in pulmonary B cells, reduced lung Treg accumulation, enhanced CD8⁺ T-cell infiltration and effector activity, and suppressed metastatic outgrowth with favorable systemic safety. These findings identify pulmonary B cells as an actionable regulator of the lung metastatic niche and establish perioperative, B-cell–focused ANXA1 silencing as a practical approach to prevent postoperative lung metastatic recurrence.
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
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2022
·
IF 4.631
Qian-Qian Nie,Zong-Qing Zheng,Juan Liao,Yu-Chao Li,Yan-Ting Chen,Tian-Ye Wang,Gui-Qiang Yuan,Zhong Wang,Qun Xue
Background: Ischemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear.Methods: Gene expression profiles of two rat ischemic stroke-related data sets, GSE61616 and GSE97537, were downloaded from the GEO database for Gene Set Enrichment Analysis (GSEA). Then, GEO2R was used to screen differentially expressed genes (DEGs). Furthermore, 170 differentially expressed intersection genes were screened and analyzed for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Candidate genes and miRNAs were obtained by DAVID, Metascape, Cytoscape, STRING, and TargetScan. Finally, the rat middle cerebral artery occlusion-reperfusion (MCAO/R) model was constructed, and qRT-PCR was used to verify the predicted potential miRNA molecule and its target genes.Results: GO and KEGG analyses showed that 170 genes were highly associated with inflammatory cell activation and cytokine production. After cluster analysis, seven hub genes highly correlated with post-stroke neuroinflammation were obtained: Cxcl1, Kng1, Il6, AnxA1, TIMP1, SPP1, and Ccl6. The results of TargetScan further suggested that miR-340-5p may negatively regulate SPP1, AnxA1, and TIMP1 simultaneously. In the ischemic penumbra of rats 24 h after MCAO/R, the level of miR-340-5p significantly decreased compared with the control group, while the concentration of SPP1, AnxA1, and TIMP1 increased. Time-course studies demonstrated that the mRNA expression levels of SPP1, AnxA1, and TIMP1 fluctuated dramatically throughout the acute phase of cerebral ischemia-reperfusion (I/R).Conclusion: Our study suggests that differentially expressed genes SPP1, TIMP1, and ANXA1 may play a vital role in the inflammatory response during the acute phase of cerebral ischemia-reperfusion injury. These genes may be negatively regulated by miR-340-5p. Our results may provide new insights into the complex pathophysiological mechanisms of secondary inflammation after stroke.
研究领域:
神经科学
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分子生物学
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基因组学
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病理生理学
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DOI
PubMed
高影响因子
Nano Today
·
2023
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IF 17.4
Honglei Zhu,Huayan Li,Kunjie Gao,Yi Huang,Yuru Liao,Weichu Hu,Feng Chen,Haoyuan Jiang,Xiaomei Liang,Haonan Song,Yuxin Wang,Hanrong Huang,Yifan Wang,Fan Liu,Hao Huang,Qian Wang,Xiao Yi
Intrauterine adhesion (IUA) is one of the main causes of female infertility. Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs), are consisted of a complete lipid bilayer structure, rich in multiple factors and miRNAs related to tissue regeneration , which are the main effective paracrine components of MSCs to treat IUA. However, the poor secretion and bioactivity of EVs leading to the unexpected therapeutic efficacy of MSC-EVs, have been obstacles to their widespread use in clinical practice. Here, we developed human chorionic villi (CV)-derived nanofibers that mimic the tissue-specific ECM microenvironment of CV-derived MSCs, maintain the stemness of MSCs for a long time, and are rich in apolipoproteins , HSP90 , ANXA1-A6, etc., which can enhance EV secretion and bioactivity. Then, the CV-nanofiber bionic culture system for mesenchymal stem cells was constructed to achieve large-scale cultivation of MSCs for continuous collection of high-concentration EVs enrichment supernatant. Additionally, EVs obtained by this system were encapsulated with CV-nanofibers to form EVs-ECM aggregate, which can effectively promote endometrium regeneration toward supporting fetal development and live births. Our study provides a new idea for enhancing EV secretion and bioactivity, and a cell-free therapy for treating IUA by EVs, thus promoting the potential of clinical application.
研究领域:
生殖医学
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干细胞生物学
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组织工程
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再生医学
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DOI
高影响因子
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