HISTOLOGY AND HISTOPATHOLOGY
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2026
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IF 2.2
Yilin Dong,Haoming Yang,Fan Yang,Liang Meng
Background: Myocardial ischemia-reperfusion (MIR) injury remains the leading cause of adverse outcomes after myocardial infarction, and its prevention remains a major therapeutic challenge. Methods: The GSE160516 and GSE61592 datasets from the Gene Expression Omnibus database were analyzed to screen MIR-related differentially expressed genes. To simulate clinical MIR injury, male C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 24 hours. Results: In this study, the protein-protein interaction network was generated based on the 34 common upregulated genes, and among them, 11 genes were identified as hub genes, including solute carrier family 11 member 1 ( Slc11a1 ), a gene associated with immune response. Herein, the upregulation of myocardial Slc11a1 was validated in mice with MIR injury. Mice subjected to MIR had improved cardiac function when Slc11a1 was knocked down via myocardial injection of Slc11a1 small interfering RNA (siRNA): the infarcted areas reduced from 38.43±4.13% to 22.18±3.45%; CK-MB levels decreased from 12.01±3.11 to 5.84±1.24. Slc11a1 silencing also reduced infiltration of F4/80 macrophages, deactivated the p65 proinflammatory pathway, and decreased the generation of IL-6 and TNF-α. Myocardial oxidative stress induced by IR challenge was attenuated in mice receiving Slc11a1 siRNA. Conclusion: Our study demonstrates that the abnormal elevation of Slc11a1 contributes to IR-related myocardial injury.
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Journal of Inflammation Research
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2025
·
IF 4.1
Huiqin Zhou,Yunjia Peng,Xinhua Huo,Bingqing Li,Huasheng Liu,Jian Wang,Gaihua Zhang
Background: Ferroptosis is a form of programmed cell death triggered by iron-dependent lipid peroxidation, characterized by iron accumulation and elevated reactive oxygen species (ROS), leading to cell membrane damage. It is associated with a variety of diseases. However, the cellular and molecular links between ferroptosis, immune inflammation, and the brain-peripheral blood axis in Alzheimer’s disease (AD) remain unclear.Methods: We integrated bulk RNA-seq data from AD brain tissue and peripheral blood and refined the screening of AD candidate genes through differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and other approaches. Additionally, we analyzed single-cell RNA-seq (scRNA-seq) data from AD patients’ brain tissue and peripheral blood, combined with scRNA-seq data from experimental autoimmune encephalomyelitis (EAE) mouse brain tissue. This enabled us to explore AD-related molecular mechanisms from a cell-type-specific perspective. Finally, candidate genes were validated in ferroptosis models using reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence methods.Results: Bulk RNA-seq analysis identified SLC11A1, an inflammatory gene associated with AD. Single-cell RNA-seq analysis further revealed that SLC11A1 expression was significantly elevated in the pro-inflammatory (M1-type) microglia and peripheral blood monocytes in AD. Moreover, we identified a microglial subpopulation in AD M1-type microglia that was highly associated with ferroptosis. This subpopulation simultaneously expressed characteristic markers of peripheral blood monocytes, suggesting that these cells may originate from peripheral blood monocytes, thereby triggering neuroinflammation through the ferroptosis pathway. Cell experiments confirmed that SLC11A1 was significantly upregulated in inflammatory microglia induced by ferroptosis.Conclusion: This study reveals the key role of SLC11A1 in AD, particularly in the context of ferroptosis and immune inflammation. It provides a novel molecular mechanistic perspective and offers potential targets for future therapeutic strategies.
研究领域:
神经科学
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分子生物学
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生物信息学
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Advanced Science
·
2026
·
IF 14.1
Lingling Qiu,Yajie Zhang,Yushi Tang,Hongli Hu,Ying Zhang,Junwen Xue,Hao Wang,Yecheng Wang,Chunfeng Liu,Jia Jia,Jian Cheng,Yongjun Cao
White matter stroke (WMS) results in demyelinating changes and neurological deficits. However, the underlying molecular mechanisms of demyelination after stroke and the specific role of microglia in white matter rehabilitation remain incompletely elucidated. This study identifies a time-dependent accumulation of iron in microglial lysosomes mediated by solute carrier family 11 member 1 (SLC11A1), which persists from 12 h to 14 days following WMS. This iron accumulation results in damaged lysosomal myelin debris uptake and degradation in microglia. Notably, iron chelation with deferoxamine (DFO), microglia-specific knockdown of SLC11A1, and administration of LM22B-10, a SLC11A1 antagonist identified in this study, effectively reduce lysosomal iron accumulation in microglia, enhance microglial uptake and clearance of myelin debris, and ultimately promote functional recovery after WMS. Furthermore, SLC11A1 functions as a H + /Fe 2+ antiporter that transports Fe 2+ from the cytoplasm into lysosomes both in vitro and in vivo. Collectively, these results highlight that targeting SLC11A1 represents a previously unrecognized therapeutic strategy for WMS repair with significant clinical implications.
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BREAST CANCER RESEARCH
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2025
·Vol. 27
·期 1
·1-19
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IF 5.6
Kong Linghui,Hu Song,Zhao Ying,Huang Yan,Xiang Xiaobing,Yu Yang,Mao Xiaochun,Xie Kangjie,Zhu Xiaoyan,Xu Pingbo
Background The mechanisms underpinning neoadjuvant chemotherapy-induced vascular endothelial injury in breast cancer remain elusive. Our study aims to demonstrate that Neutrophil Extracellular Traps (NETs) play a pivotal role in neoadjuvant chemotherapy-induced vascular endothelial injury in breast cancer, elucidating that chemotherapy-induced upregulation of Solute Carrier 11a1 (Slc11a1) modulates Reactive Oxygen Species (ROS) generation, which may be critical for NETs formation.Methods We investigated the impact of neoadjuvant chemotherapy for breast cancer on NETs formation and vascular endothelial injury by analyzing NETs dsDNA and serum markers in patients, cells, and chemotherapy mouse models. RNA sequencing of neutrophils from chemotherapy mouse models was performed to identify the potential NETs formation-associated gene Slc11a1, which was further validated through cellular and animal experiments by assessing Slc11a1 expression, intracellular ferrous ion content, and ROS levels. Knockdown of Slc11a1 in human neutrophils and mouse models were also performed to further confirm the phenotypic results.Results Our study revealed that plasma NETs formation and endothelial injury markers were significantly elevated in breast cancer patients undergoing docetaxel & carboplatin (TCb) neoadjuvant chemotherapy, compared to controls. In these patients, NETs formation was associated with the augmentation of endothelial injury markers. Chemotherapy mouse models demonstrated that TCb treatment markedly elevated NETs formation and endothelial injury, which can be mitigated by CI-amidine, a protein-arginine deiminase inhibitor. In human neutrophils, we demonstrated that the TCb chemotherapeutic agents (combination of docetaxel and carboplatin) induced the formation of NETs, which subsequently facilitated damage to human umbilical vein endothelial cells in vitro. RNA sequencing of mouse neutrophils identified Slc11a1 as a key NETs formation-related gene, which was upregulated by TCb chemotherapy in neutrophils, leading to increased intracellular ferrous ion content and ROS generation. Knockdown of Slc11a1 in human neutrophils and mouse models demonstrated its reversal effect on TCb-induced ferrous ion upregulation, ROS generation, and NETs formation.Conclusion sOur research underscores the capacity of TCb neoadjuvant chemotherapy in breast cancer to augment NETs formation in neutrophils through Slc11a1-mediated ROS generation, which is linked to vascular endothelial injury. Our study elucidates the potential mechanisms underlying perioperative vascular endothelial injury in breast cancer patients undergoing neoadjuvant chemotherapy, offering novel insights into perioperative therapeutic management strategies for these patients.
研究领域:
肿瘤学
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免疫学
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分子生物学
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