Bioengineering & Translational Medicine
·
2025
·
IF 5.7
Lulu Chen,Bicheng Chen,Xiang Su
An abdominal aortic aneurysm (AAA) is a life-threatening vascular condition characterized by the dilation of the abdominal aorta, with ferroptosis playing a significant role in its pathogenesis. This study investigates the therapeutic potential of engineering biomimetic nanovesicles to deliver phosphatidylethanolamine-binding protein 1 (PEBP1) mRNA for inhibiting ferroptosis in vascular smooth muscle cells (VSMCs) and preventing AAA progression. Differential gene expression analysis of the AAA transcriptomic dataset GSE57691 identified 243 differentially expressed genes (DEGs), intersecting with 12 ferroptosis-related genes. Single-cell analysis of dataset GSE237230 highlighted PEBP1 as a key gene in VSMCs. Overexpression of PEBP1 in VSMCs enhanced proliferation, reduced reactive oxygen species (ROS) and iron levels, and inhibited apoptosis and ferroptosis via the NRF2/GPX4 axis. The engineered biomimetic nanovesicles demonstrated significant uptake by VSMCs and effective delivery of PEBP1 mRNA. In vivo studies confirmed that these nanovesicles substantially inhibited AAA progression in mice. This study presents a novel bioengineering approach for AAA treatment by targeting ferroptosis through PEBP1 mRNA delivery, offering a promising molecular strategy for the prevention and management of AAA.
研究领域:
生物医学工程
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纳米技术
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分子生物学
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心血管疾病研究
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基因治疗
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产品关联
DOI
PubMed
高影响因子
eLife
·
2025
·
IF 0
Ling Cheng,Ian Meliala,Yidi Kong,Jingyuan Chen,Christopher G Proud,Mikael Björklund
Mitochondrial dysfunction is involved in numerous diseases and the aging process. The integrated stress response (ISR) serves as a critical adaptation mechanism to a variety of stresses, including those originating from mitochondria. By utilizing mass spectrometry-based cellular thermal shift assay (MS-CETSA), we uncovered that phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitory protein (RKIP), is thermally stabilized by stresses which induce mitochondrial ISR. Depletion of PEBP1 impaired mitochondrial ISR activation by reducing eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and subsequent ISR gene expression, which was independent of PEBP1’s role in inhibiting the RAF/MEK/ERK pathway. Consistently, overexpression of PEBP1 potentiated ISR activation by heme-regulated inhibitor (HRI) kinase, the principal eIF2α kinase in the mitochondrial ISR pathway. Real-time interaction analysis using luminescence complementation in live cells revealed an interaction between PEBP1 and eIF2α, which was disrupted by eIF2α S51 phosphorylation. These findings suggest a role for PEBP1 in amplifying mitochondrial stress signals, thereby facilitating an effective cellular response to mitochondrial dysfunction. Therefore, PEBP1 may be a potential therapeutic target for diseases associated with mitochondrial dysfunction.
研究领域:
细胞生物学
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分子生物学
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应激反应
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线粒体疾病
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DOI
PubMed
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.2
Jia-Gen Cui,Hao Zhang,Ming-Shan Chen,Jia-Xin Wang,Xue-Nan Li,Jin-Long Li
Lycopene (LYC), a natural antioxidant compound abundant in tomatoes, has established neuroprotective roles due to its antioxidant and anti-inflammatory properties. Di (2-ethylhexyl) phthalate (DEHP), a common plasticizer, is known to exert neurotoxic effects. However, the mechanisms of DEHP-induced neurotoxicity remain unclear. Furthermore, effective preventive strategies against this neurotoxicity are still lacking. This study, employing in vitro (BV2 cells) and in vivo (ICR mouse) models, demonstrates that LYC prevents DEHP-induced cerebellar damage by suppressing the triggering of dose-dependent microglial ferroptosis and neuroinflammation. Mechanistically, LYC inhibited the phosphatidylethanolamine-binding protein 1 (PEBP1)/arachidonate 15-lipoxygenase (ALOX15) axis (supported by immunofluorescence and Western blot assays), leading to reduced reactive oxygen species by approximately 48% in the cerebellum, which ultimately prevented neuroinflammation. Our findings reveal that LYC prevents DEHP-induced neurotoxicity by inhibiting microglial ferroptosis via the PEBP1/ALOX15 axis. Furthermore, our findings highlight the clinical promise of LYC as a novel neuroprotective treatment against environmental toxicant-induced damage.
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DOI
PubMed
高影响因子
International Journal of Oral Science
·
2023
·Vol. 15
·期 1
·1-14
·
IF 14.9
Wang Yushang,Wang Lihua,Sun Tianyong,Shen Song,Li Zixuan,Ma Xiaomei,Gu Xiufeng,Zhang Xiumei,Peng Ai,Xu Xin,Feng Qiang
Fusobacterium nucleatum ( F. nucleatum ) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum -infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum -infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
研究领域:
微生物学
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免疫学
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分子生物学
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干细胞研究
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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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