Burns & Trauma
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2026
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IF 9.6
Deng Shuang,Ying Ting,Zhang Xu,Ghorbani Farnaz,Luo Wen,Yi Chengqing,Li Dejian
BackgroundPersistent oxidative stress and aberrant inflammatory responses are major contributors to delayed wound healing in diabetic patients. Endothelial cell pyroptosis, a form of inflammatory programmed cell death, plays a critical role in vascular dysfunction and impaired tissue regeneration in diabetic wounds. Targeting endothelial pyroptosis therefore represents a promising therapeutic strategy. This study aims to develop a multifunctional nanofibrous scaffold capable of suppressing oxidative stress-induced endothelial pyroptosis while modulating the inflammatory microenvironment to promote angiogenesis and diabetic wound repair.MethodsIn this study, a pH-responsive nanoplatform based on zinc–imidazolate metal–organic frameworks (ZIF-8) was constructed for the controlled delivery of luteolin (Lut), a natural flavonoid with anti-inflammatory and antioxidant properties. The physicochemical characteristics, drug-loading efficiency, and pH-responsive release behavior of Lut@ZIF-8 nanoparticles were systematically evaluated. The effects of Lut@ZIF-8 on oxidative stress, endothelial pyroptosis, and angiogenic function were investigated in vitro, while therapeutic efficacy was further assessed in a diabetic mouse wound model using Lut@ZIF-8-loaded fibrous scaffolds.ResultsLut@ZIF-8 nanoparticles exhibited uniform morphology, high drug-loading efficiency, and sustained drug release under mildly acidic conditions mimicking the diabetic wound microenvironment. In vitro, Lut@ZIF-8 effectively suppressed reactive oxygen species accumulation and inhibited endothelial cell pyroptosis by downregulating the activation of NLRP3 inflammasome components, including caspase-1 and GSDMD, thereby preserving endothelial barrier integrity and angiogenic capacity. In vivo, Lut@ZIF-8-loaded scaffolds significantly reduced inflammatory cytokine expression, enhanced collagen deposition, promoted neovascularization and re-epithelialization, and ultimately accelerated wound closure in diabetic mice.ConclusionsThe pH-responsive Lut@ZIF-8 nanoplatform effectively modulates oxidative stress and endothelial cell pyroptosis in diabetic wounds, thereby promoting angiogenesis and tissue regeneration. This strategy provides a promising and innovative therapeutic approach for the treatment of chronic diabetic wounds.
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DOI
高影响因子
LIFE SCIENCES
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2026
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IF 6.4
Fengzhen Huang,Jiping Yi,Tieqiao Zhou,Jibao Wu,Xiaojing Li,Heng Meng,Xiaoxiang Gong
Background YTHDF3 expression is up-regulated in sepsis-associated encephalopathy (SAE), yet its precise function remains to be fully elucidated. This study aims to investigate the role of YTHDF3 in microglial pyroptosis during SAE and to explore its upstream and downstream regulatory mechanisms. Methods Lipopolysaccharide (LPS) induced SAE models were established in mice and primary microglia for the assessment of YTHDF3 and pyroptosis levels. Downstream targets of YTHDF3 were identified through RNA sequencing and RNA immunoprecipitation. Ultimately, chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) was utilized to confirm H3K18la enrichment at the YTHDF3 promoter. Results In both in vitro and in vivo models of SAE, YTHDF3 expression was significantly upregulated. Crucially, YTHDF3 knockdown effectively attenuated NLRP3-mediated microglial pyroptosis, thereby alleviating neuroinflammation and restoring cognitive function in SAE mice. Mechanistically, Usp9x acted as a direct downstream target of YTHDF3 to mediate the deubiquitination of NLRP3, which in turn augmented microglial pyroptosis in SAE. Furthermore, the transcriptional upregulation of YTHDF3 was promoted by H3K18la enrichment at its promoter. Inhibition of the lactylation-driven YTHDF3/Usp9x/NLRP3 signaling axis attenuates microglial pyroptosis and ameliorates cognitive dysfunction in SAE models. Conclusion Lactylation-driven YTHDF3 promotes microglial pyroptosis and cognitive impairment in SAE by targeting the Usp9x/NLRP3 axis. Our findings highlight this axis as a potential therapeutic target for SAE. Download: Download high-res image (123KB) Download: Download full-size image
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高影响因子
BIOMATERIALS
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2026
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IF 13.6
Zheng Deng,Xirui Wu,Tianhao Huang,Huiyuan Chen,Zhuochao Wu,Li Liu,Yuqian Liu,Chunjie Wang,Zijian Xiong,Zhuang Liu,Guangbao Yang
Intracellular polyamine metabolic homeostasis is closely linked to therapeutic outcomes in cancer. However, their intrinsic antitumor mechanisms have not been fully clarified. Herein, we demonstrate that the catabolism of spermine (Spm) and spermidine (Spd) mediated by polyamine oxidase directly generates two potent cytotoxic metabolites, namely acrolein and hydrogen peroxide. These metabolites act synergistically to trigger a marked elevation in intracellular reactive oxygen species (ROS), which in turn activate the caspase-1/GSDMD and caspase-3/GSDME signaling pathways, ultimately driving tumor cells into pyroptosis. Based on these findings, we develop a phenylboronic acid-functionalized sodium alginate-based hydrogel controlled-release system (Alg-PBA/Spd). This platform achieves sustained Spd release through coordination interactions and markedly inhibits tumor growth by inducing pyroptosis. Further studies demonstrate that the Alg-PBA/Spd hydrogel synergizes with radiotherapy (RT) to enhance radiosensitivity in an orthotopic breast cancer model and inhibit pulmonary metastasis. Moreover, this hydrogel enables co-delivery of αPD-L1 with sustained release, which significantly improves the response rate of immune checkpoint blockade therapy by inducing pyroptosis and remodeling the tumor immune microenvironment. Overall, this study not only elucidates a previously unrecognized mechanism underlying polyamine metabolism-driven pyroptosis but also offers a versatile platform to enhance the efficacy of RT and immunotherapy.
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高影响因子
RESPIRATORY RESEARCH
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2026
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IF 5.7
Li Min,Guo Jiayao,Li Xianmei,Zheng Jialin,Yang Weimin,Luo Zhuang,Zhu Wenye
Background Asthma is a highly heterogeneous chronic respiratory disease, and accumulating evidence indicates a role for pyroptosis in its pathogenesis. However, few studies have identified pyroptosis-related asthma subtypes or systematically evaluated the role of pyroptosis-related genes (PRGs) in asthma. Methods We utilized GSE137268 to conduct Gene Set Variation Analysis (GSVA) to assess pyroptosis enrichment scores in patients with asthma compared to healthy controls. We then confirmed the differences in pyroptosis levels in murine asthma models. Next, we grouped asthma cases from the dataset using consensus clustering based on the PRG expression profiles. We used Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single sample Gene Set Enrichment Analysis (ssGSEA) to analyze the biological functions and immune status of each subgroup. We constructed a protein-protein interaction (PPI) network to identify hub genes within these subtypes, and subsequently validated these genes using an independent dataset, GSE45111. Receiver operating characteristic (ROC) curves were applied to assess the discriminatory capacity of hub genes. Results Asthma samples exhibited significantly higher pyroptosis enrichment scores than control samples. The expression of IL-1β, IL-18 and GSDMD-N was elevated in murine asthma models. We identified two pyroptosis-related asthma subtypes: Cluster 1 and Cluster 2. Cluster 1 exhibited heightened inflammation, manifesting as eosinophilic, neutrophilic, and mixed granulocytic phenotypes, while Cluster 2 was linked to paucigranulocytic asthma with reduced inflammation. Analyses of GO, KEGG, and ssGSEA revealed clear differences in biological functions and immune profiles between the two subtypes. The PPI network analysis identified five hub genes: IL1B , TLR2 , MMP9 , ICAM1 , and NLRP3 . Receiver operating characteristic (ROC) analyses further indicated the discriminative power of these five genes in distinguishing Cluster 1 from Cluster 2. Clustering analysis in GSE45111 produced results consistent with those from GSE137268. Conclusions Aberrant pyroptosis is associated with airway inflammation in asthma. The subtypes, identified based on PRG expression profiles, showed distinct clinical features, gene expression patterns, biological functions, and inflammatory profiles, suggesting a role for pyroptosis in asthma heterogeneity.
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高影响因子
TISSUE & CELL
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2025
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IF 2.5
Minhui Wang,Daojun Chen,Daofa Zhang,Hui Han,Maowei Xie,Ying Zhang,Yun Cao,Jiali Wei
Background Renal fibrosis (RF) is a common histopathological feature of chronic kidney disease (CKD) and is closely associated with persistent inflammation and regulated cell death. However, the underlying molecular mechanisms of pyroptosis in RF are unclear. Methods Pyroptosis-related hub genes in RF were identified through bioinformatics analysis. Granzyme B ( GZMB ) was knocked down in transforming growth factor (TGF-β)-stimulated HK-2 cells and in a folic acid (FA)-induced nephropathy mouse model. Western blot and enzyme-linked immunosorbent assays were performed to detect the expression of fibrosis and pyroptosis-related markers. Cell viability was assessed by the Cell Counting Kit-8 assay. Hematoxylin and eosin (HE) and Masson's staining were used to evaluate tubular injury and collagen deposition in renal tissues. Results GZMB was identified as a pyroptosis-associated hub gene. It was significantly upregulated in RF and exhibited high diagnostic performance. In TGF-β-stimulated HK-2 cells, GZMB knockdown enhanced cell viability and reduced lactate dehydrogenase release. In vivo , GZMB silencing ameliorated tubular injury, reduced collagen deposition, and improved renal function. The expression levels of pyroptosis-related proteins, including the N-terminal fragment of gasdermin D, cleaved caspase-1, and NOD-like receptor family pyrin domain containing 3 (NLRP3), as well as fibrotic markers alpha-smooth muscle actin and collagen type I, were downregulated after GZMB knockdown. Mechanically, GZMB knockdown inhibited NLRP3 inflammasome activation and suppressed the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. Conclusion GZMB deficiency inhibits pyroptosis and dampens the JAK2/STAT3 pathway, representing a potential approach for RF treatment.
研究领域:
肾脏病学
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分子生物学
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细胞信号传导
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炎症
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纤维化研究
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DOI
PubMed
高影响因子
DALTON TRANSACTIONS
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2025
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IF 3.3
Yuan Xu,Ya-Tao Hu,Jiaping Cao,Dixin Lin,Qiqi Zhong,Yi Wang,Hongdong Shi,Qianling Zhang
To address the challenges associated with low cellular uptake efficiency of metal-based anticancer agents and the suboptimal therapeutic efficacy of photodynamic therapy (PDT), a series of polypyridyl ruthenium(II) complexes (Ru Cn) with tunable carbon chain lengths were rationally designed and synthesized through the incorporation of fatty acid moieties, which confer enhanced lipid solubility and membrane-targeting capabilities. Among these, the octadecanoic acid-modified ruthenium complex (Ru-C18) exhibited superior anticancer activity. Cytotoxicity assays demonstrated that Ru-C18 displayed sub-molar cytotoxic potency under light irradiation. Co-localization studies confirmed its preferential accumulation in lysosomes after cellular internalization. Upon light activation, Ru-C18 efficiently generated singlet oxygen and induced hallmark features of pyroptosis, including plasma membrane blebbing, cellular swelling, and Gasdermin-dependent membrane pore formation. Consequently, Ru-C18 significantly suppressed tumor cell proliferation via activation of the pyroptotic pathway. These findings offer new insights into the rational design of highly effective and selectively targeted photodynamic anticancer agents.
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2025
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IF 5.7
Lili Liu,Wenting Ye,Yanqiu Duan,Xinran Song,Li Ding,Yu Chen,Meiqi Chang
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder marked by dysregulated immune responses and pyroptosis of intestinal epithelial cells, a type of programmed cell death that aggravates inflammation. Current therapeutic strategies frequently encounter limitations in both efficacy and specificity. Herein, we developed a calcium manganese-based (CaMn2O4) pancatalytic nanozyme designed to mitigate pyroptosis and alleviate IBD symptoms. The calcium manganese-based nanozyme exhibits dual enzyme (catalase and superoxide dismutase)-mimetic catalytic activities, scavenging reactive oxygen species and suppressing GSDMD cleavage, a key mediator of pyroptosis. In vitro studies demonstrated that CaMn2O4 nanozyme significantly reduced pyroptotic cell death in lipopolysaccharide/nigericin-stimulated cells. In a murine colitis model, CaMn2O4-based nanozyme treatment attenuated inflammatory infiltration, preserved epithelial barrier integrity, and downregulated pyroptosis-related markers. This study highlights the potential of pancatalytic nanotherapy targeting pyroptosis as a novel strategy for IBD treatment.
研究领域:
纳米医学
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免疫学
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胃肠病学
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生物无机化学
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酶学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Ru-Yang Zhao,Mu-Zi Li,Qi-Qian Wang,Fu-Wei Jiang,Yi Zhao,Jin-Long Li
Butachlor (BTR), a globally prevalent amide herbicide, poses significant environmental health risks due to its bioaccumulation potential and documented chronic toxicity in mammalian systems. Given the spleen's pivotal role in orchestrating systemic immune homeostasis, this study investigated BTR-induced immunopathological mechanisms in ICR mice following 28-day subacute exposure (10 mg/kg). Histopathological examination revealed significant disorganization of the splenic marginal zone architecture, concomitant with ultrastructural mitochondrial abnormalities and a reduction in mitochondrial membrane potential (ΔΨm). Mitochondrial permeability transition pore opening triggered cytoplasmic translocation of mitochondrial DNA (mtDNA), activating the stimulator of interferon genes (STING) pathway—a master regulator of innate immunity. STING activation initiated bifurcated downstream signaling, evidenced by TBK1 phosphorylation and subsequent IRF3 / NF-κB nuclear translocation. This dual signaling cascade simultaneously executed immunogenic cell death via Gasdermin D-dependent pyroptosis (cleaved GSDMD-NT) and drove macrophage polarization (IFN-α / β, IL-1β, TNF-α). Crucially, pharmacological STING inhibition with C-176 attenuated both pyroptosis (GSDMD cleavage reduced) and inflammatory cytokine surge. Our findings not only pioneer the identification of the mtDNA-STING axis as the central mechanism underlying BTR-induced splenic immunotoxicity but also validate STING inactivation as a targeted strategy to mitigate herbicide-associated immune dysfunction. This work provides critical insights for environmental toxicant risk assessment and immunomodulatory.
研究领域:
环境毒理学
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免疫学
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分子生物学
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药理学
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细胞生物学
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PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
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2025
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IF 4.4
Shuang Guan,Yuanmeng Wang,Ranran Zhang,Xinyu Yao,Shujing Lu,Xuming Deng,Jing Lu
Alcohol, one of the most widely popular and consumed beverages worldwide, often leads to acute alcoholic liver injury (AALI) when excessively consumed within a short timeframe. It can further induce alcoholic hepatitis, posing a serious risk to human health and public health safety. Pyroptosis, a typical mode of programmed cell death, is closely associated with the body's inflammatory response and plays a central role in AALI. However, the role of yogurt in acute alcohol-induced pyroptosis and inflammation is unclear. In this study, we found that yogurt and its metabolite d -lactate effectively mitigate alcohol-induced liver damage in mice, reducing hepatocyte pyroptosis and attenuating the inflammatory response. For the specific mechanism, further studies have shown that yogurt may inhibit autophagy through its substance d -lactate, leading to the accumulation of P62 protein in cells. This accumulation subsequently triggers the activation of Nrf2 through nonclassical pathways. Nrf2 translocates to the nucleus to play its antioxidant role, thereby reducing intracellular reactive oxygen species levels, inhibiting the activation of the alcohol-induced NLRP3 inflammasome, and ultimately alleviating pyroptosis and inflammation. Overall, this study reveals the potential protective effect of yogurt and its metabolite d -lactate in alleviating AALI, offering new insights and scientific basis for yogurt as a dietary strategy to improve AALI.
研究领域:
肝病学
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营养学
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分子生物学
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免疫学
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药理学
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细胞生物学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Zong-hui Xu,Man Li,Lin Liu,Shu-jing Wu,Ruo-an Wei,Mpofu Uphakeme Inobubele Sitholumusa,Xiao-ping Zhao,Jun-qiu Liu,Guo-yin Kai
Astragaloside IV (AS-IV), derived from Astragalus membranaceus , exhibits significant anti-inflammatory properties in a variety of diseases. However, the specific anti-inflammatory mechanism of AS-IV depends on the different organs and doses. Its protective effect is still unknown in acute lung injury (ALI). This study aims to investigate the potential anti-inflammatory mechanism of AS-IV in ALI. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were utilized to form pyroptosis models in MH-S and RAW264.7 cells. Mouse model of ALI was induced by intranasal LPS administration. In addition, the anti-pyroptosis effect of AS-IV was evaluated by using the C5aR1 agonists BM-213, the C5aR1 overexpression plasmids and C5aR1 siRNA. AS-IV significantly reduced pulmonary edema, improved histopathological injury, and decreased inflammatory factors. Meanwhile, AS-IV reduced ROS level and the amount of NLRP3 and GSDMD-N in vitro and in vivo . Inhibiting C5aR1 can effectively and significantly alleviate the pyroptosis of alveolar macrophages. Further studies found that BM-213 and C5aR1 overexpression plasmids partially reversed the anti-pyroptosis effect of AS-IV. The anti-pyroptosis effect of AS-IV was significantly inhibited when C5aR1 was knocked down. Our study demonstrate that AS-IV has anti-inflammatory protective effects on LPS-induced ALI, indicating that AS-IV may be a potential therapeutic agent for the treatment of ALI. This effect may be achieved by reducing the content of C5a, lowering the expression of C5aR1, and inhibiting cell pyroptosis.
研究领域:
药理学
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免疫学
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分子生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Wenwu Zhu,Yao Lu,Bin Zong,Ziyi Chen,Yong Ma,Haoran Wang,Peng Cao,Bing Han
The ideal treatment for myocardial infarction should address the critical issues of oxygen supply improvement in the infarcted area and prevention of myocardial cell death. Myocardial necrosis is a reversible process, but the challenge lies in mitigating the irreversible pyroptosis of cardiomyocytes, which significantly impedes the recovery of cardiac function. To tackle these complexities, here we have developed MnO2@INN@Alb (MIA) nanoparticles. MIA nanoparticles possess the unique ability to generate oxygen and release glibenclamide (INN) in response to the acidic and H2O2-rich environments present in the infarcted region. MIA plays a dual role by inhibiting the pyroptosis process of cardiomyocytes through the suppression of NLRP3 and by providing vital oxygen to alleviate hypoxia. The results shows that MIA can effectively reverse cardiomyocyte hypoxia, reduce infarct fibrosis, and aid in the reconstruction of myocardial vessels. Moreover, MIA demonstrates high biocompatibility, making it a promising avenue for the future of myocardial infarction improvement. We anticipate that MIA can pave the way for novel solutions and research paradigms in the field.
研究领域:
生物学
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医学
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药理学
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生物材料
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DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Qian Wu,A-Ling Tang,Qing-Qing Dong,Bing-Qing Chen,Yi Shi,Xiao-Ling Xu,Wei Chen,Wei Chen
Sepsis still remains the leading cause of morbidity and mortality in clinical settings, characterized by pyroptosis-induced cytokine release syndrome, multiple organ dysfunction, and gut microbiota disturbances. Inhibiting the pyroptosis pathway by nanosystems represents a potential therapeutic strategy for the treatment of sepsis. However, current pharmacological interventions primarily focus on blocking reactive oxygen species (ROS)/NOD-like receptor pyrin domain-containing 3 (NLRP3)/Caspase-1-based pyroptosis rather than lipopolysaccharide (LPS)-triggered pyroptosis. Besides, given the importance of microbiota disturbances in a second wave of cytokine storms, the assessment of the composition of intestinal flora after treatment was also missing. Herein, picroside II-encapsulated, palmitic acid-modified nanoformulations were prepared as a pyroptosis modulator to inhibit cytokine release syndrome, accompanied by reprogramming the composition of intestinal flora. Results demonstrated that the modification of palmitic acid on nanoformulations promotes the cellular uptake of nanoparticles via Toll-like receptor-mediated specific recognition. The sustained release of picroside II scavenged the massive reactive oxygen species, reduced the levels of inflammatory factors, and downregulated the pyroptosis-related proteins. Furthermore, the interaction between palmitic acid and Toll receptors reduced the combination site of LPS, providing a positive loop in drug delivery and inhibiting pyroptosis. Consequently, the obtained nanoformulations exerted a better antioxidant, anti-inflammatory, and antiproptosis activity than other treatment groups, thereby alleviating LPS-stimulated multiorgan damage, especially the kidney and colon. Interestingly, it also improved the abundance of intestinal flora, contributing to enhanced intestinal barrier function and improved immune system. Thus, palmitic acid-anchored, picroside II-encapsulated nanoformulations potentiated a systematic and desirable therapeutic outcome in sepsis treatment.
研究领域:
纳米医学
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免疫学
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微生物学
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药理学
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分子生物学
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生物医学工程
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PubMed
高影响因子
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