AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
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2025
·Vol. 93
·期 5
·e70084
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IF 2.4
Heng Wang,Zhaofei Liu,Xiangjun Xu,Haitao Zhang,Lei He,Ming Li
Background Chronic prostatitis (CP), a frequent male urological disease, is featured with chronic pelvic pain and various discomfort. Calycosin has anti-inflammatory effect and its exact mechanism in CP remains unknown. Objective Our research was designed to explain the underlying mechanism of calycosin in CP and illustrate our findings in the rats and LPS-ATP-induced RWPE-1 cells. Methods The pathology of prostate tissues was analyzed by HE staining and histological inflammation score. The concentration of inflammatory factors were detected via ELISA assay. Besides, the representative biomarkers of oxidative stress were measured through detection kits. The ROS production, NLRP3 and GSDMD expression were evaluated by immunofluorescence or immumohistochemical staining. Furthermore, the expression of NF-kBp65 pathway-associated proteins and pyroptosis-associated proteins were detected by western blotting. RWPE-1 cells growth and pyroptosis were assessed by CCK-8 and flow cytometry, respectively. mRNA levels of pyroptosis markers were detected by qRT-PCR analysis. Results The CP model in vivo and in vitro was successfully established by carrageenan and LPS-ATP, respectively. Calycosin substantially ameliorated the pathological damage of prostate tissue. Moreover, calycosin treatment promoted RWPE-1 cells viability and reduced pyroptosis. Calycosin remarkably reduced the inflammatory factors secretion and oxidative stress markers. Calycosin stimulation effectively suppressed the pyroptosis, which was linked with inactivation of the NF-kBp65 signaling pathway. These beneficial effects of calycosin were similar to the NLRP3 inhibitor (MCC950). Conclusion To sum up, our observations indicated that calycosin protects against CP via suppressing inflammation, oxidative stress, and pyroptosis through NF-kBp65 pathway, thereby serving as a promising therapy for CP treatment.
研究领域:
医学
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药理学
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免疫学
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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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Scientific Reports
·
2024
·Vol. 14
·期 1
·1-12
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IF 3.8
Gao Kexin,Liu Yancui,Sun Cheng,Wang Ying,Bao Hongrong,Liu Guoyang,Ou Jinrui,Sun Ping
Pyroptosis is a gasdermin-mediated pro-inflammatory form of programmed cell death (PCD). Tumor necrosis factor-ɑ (TNF-ɑ) is an inflammatory cytokine, and some studies have shown that TNF-ɑ can cause pyroptosis of cells and exert anti-tumor effects. However, whether TNF-ɑ exerts anti-tumor effects on breast cancer cells by inducing pyroptosis has not been reported. In this study, to explore the impact of TNF-ɑ on pyroptosis in breast cancer cells, we treated MCF-7 cells with TNF-ɑ and found that TNF-ɑ induced cell death. Moreover, we observed that the dead cells were swollen with obvious balloon-like bubbles, which was a typical sign of pyroptosis. Further studies have found that the anti-tumor effect of TNF-ɑ on breast cancer cells in vitro was achieved through the canonical pyroptosis pathway. In addition, TNF-ɑ-induced pyroptosis in MCF-7 cells was associated with mitochondrial dysfunction, in which mitochondrial membrane potential was decreased and mitochondrial ROS production was increased. After inhibiting ROS production, the activation effect of TNF-ɑ on NLRP3/Caspase-1/GSDMD pathway was weakened, and the inhibitory effect of TNF-ɑ on the growth of MCF-7 cells in vitro was also decreased, further confirming the involvement of ROS in TNF-ɑ-induced pyroptosis. Overall, our study revealed a new mechanism by which TNF-ɑ exerts an anti-tumor effect by inducing pyroptosis in MCF-7 cells through the ROS/NLRP3/Caspase-1/GSDMD pathway, which may provide new therapeutic ideas for the treatment of breast cancer.
研究领域:
肿瘤学
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细胞生物学
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免疫学
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高影响因子
Journal of Materials Chemistry B
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2026
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IF 6.2
Chunyan Niu,Wen Gao,Mei Tan,Yue Chen,Yongqiang Shi,Yan Geng,Huayi Tao,Zhenjiang Xu,Tingting Zhang,Jinming Yang
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic stress-induced hepatic injury closely associated with insulin resistance and genetic predisposition, affecting about 25% of the global population and becoming the leading cause of chronic liver disease. Therapeutic interventions targeting the regulation of inflammation-related pathways have shown potential for significant improvements in MASLD treatment. Herein, we developed galactose-decorated lipid nanoparticles for selective NLRP3 inhibitor targeted liver delivery (MCC950@Gal-LNPs). The galactose modification endowed the LNPs with liver-targeting ability via asialoglycoprotein receptor (ASGPR)-based hepatocellular uptake. The MCC950-loaded formulation effectively reduced the expression of inflammatory regulators and cytokines associated with the NF-κB/NLRP3-related signaling pathway. The Gal-LNPs improved MCC950 accumulation in the liver compared to non-targeted formulations and effectively reduced inflammatory signal activation in vivo. Moreover, MCC950 treatment significantly improved fibrosis by reducing the fibrotic area and normalizing tissue morphology. Therefore, MCC950@Gal-LNPs significantly reduces the inflammatory microenvironment, and MCC950, as a novel NLRP3 inhibitor, appears to be an attractive assay for the effective treatment of NASLD.
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Chinese Medicine
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2026
·Vol. 21
·期 1
·87
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IF 7.4
Li Yuan,Han Dongyang,Liu Junjie,Qiao Yuxin,Wei Jiaoxia,Lu Haitao,Yao Li
Background Pulmonary hypertension (PH) is a severe pulmonary vascular disease lacking early diagnostic biomarker and effective therapeutics. Osthole has capability to alleviate pulmonary vascular remodeling targeting by decadienyl-L-carnitin (C10:2) in PH rats. We sought to explore the novel functional mechanism of C10:2 in cell proliferation, apoptosis, extracellular matrix remodeling, and energy biosynthesis of pulmonary vascular remodeling as well as new inventional mechanism of osthole. Methods Animal and cell models of PH were established using monocrotaline (MCT) and platelet-derived growth factor-BB (PDGF-BB). C10:2 biosynthesis was manipulated through the administration of exogenous C10:2 and etomoxir. Markers of pyroptosis and pulmonary vascular remodeling, as well as components of the C10:2/HSP47/NLRP3 axis, were evaluated using western blotting, ELISA, and biochemical assays. Results Osthole inhibited cell pyroptosis and alleviated pulmonary vascular remodeling by suppressing the expression of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, and C10:2 in PH rats. Additionally, C10:2 levels were positively correlated with the progression of pulmonary vascular remodeling in a time-dependent manner. C10:2, similar to PDGF-BB, promoted the proliferation of pulmonary arterial smooth muscle cells (PASMCs), accelerated extracellular matrix remodeling, inhibited apoptosis, activated AMPKα-1, and increased ROS accumulation, ultimately leading to mitochondrial dysfunction in PASMCs. Osthole attenuated C10:2-induced pulmonary vascular remodeling by downregulating proliferation markers (PCNA, cyclin A, CDK2), modulating apoptosis markers (Caspase-3, Bax, Bcl-2), inhibiting migration-related proteins (MMP2, MMP9, TGF-β), and reducing AMPKα-1 and ROS overaccumulation as well as HSP47 expression. Collectively, our findings reveal a novel role for C10:2 in accelerating pulmonary vascular remodeling by promoting proliferation, apoptosis resistance, extracellular matrix remodeling, and mitochondrial dysfunction through NLRP3 inflammasome activation. Mechanistically, osthole significantly inhibited pyroptosis and mitigated pulmonary vascular remodeling via the C10:2/HSP47/NLRP3 axis. Conclusion Our study identifies a novel function of C10:2 in promoting pyroptosis and accelerating pulmonary vascular remodeling through activation of the HSP47/NLRP3 axis. Furthermore, we demonstrate that osthole effectively inhibits C10:2/HSP47/NLRP3 axis-induced pyroptosis, thereby alleviating pulmonary vascular remodeling. These findings suggest that C10:2 may serve as a potential biomarker for PH diagnosis and provide a foundation for the development of novel anti-PH therapeutic strategies. Graphical
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Cell Death & Disease
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2026
·Vol. 17
·期 1
·226
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IF 12.2
Rao Yongjuan,Wang Yunran,Gao Jie,Guan Xun,Lv Sixuan,Gu Junlian,Wang Kefang
Overactive bladder (OAB) is strongly linked to intravesical inflammatory responses. Transient receptor potential ankyrin-1 (TRPA1) is a key sensor and signaling molecule in bladder function, crucial for initiating and maintaining inflammation. However, the mechanisms underlying TRPA1-mediated inflammatory processes in OAB remain unclear. This study aims to elucidate the molecular mechanisms of TRPA1 and the contribution of inflammatory pathways to OAB. Elevated TRPA1 expression was observed in urinary sediment cells from OAB patients and in bladder tissues from OAB animal models. Mechanistically, TRPA1 drives the progression of OAB by activating the Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome and triggering pyroptosis. Notably, treatment with HC-030031 effectively mitigated inflammatory responses and restored bladder function, whereas Nlrp3 overexpression negated these therapeutic benefits. Furthermore, TRPA1-mediated upregulation of NLRP3 was dependent on the transcription factors MAZ and SMAD3, highlighting a novel regulatory axis. Our findings establish TRPA1 as a pivotal mediator in the progression of OAB by activating the NLRP3 inflammasome and thereby inducing pyroptosis. Targeting TRPA1 or the NLRP3 signaling pathway represents a promising therapeutic strategy for OAB, offering new insights into disease management and potential improvements in patient outcomes.
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CHEMISTRY & BIODIVERSITY
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2022
·Vol. 20
·期 1
·e202200985
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IF 2.745
De-Wen Bi,Ying-Xin Zhao,Xiong Qiu,Xue-Cong Zhang,Ya-Ling Zhou,Muhammad Aurang Zeb,Wen-Hui Pang,Rui Li,Meng-Ru Wang,Bin Cheng,Jing-Jing Zhang,Xing-Jie Zhang,Xiao-Li Li,Rui-Han Zhang,Wei-Lie Xiao
Twelve new clerodane diterpenoids named callicarpanes A–L ( 1 – 12 ), together with eight known compounds ( 13 – 20 ), were isolated from Callicarpa integerrima . Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1 , 3 , 5 , 9 , 10 , 12 , 15 , 16 , and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC 50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 μM. Further study revealed that compound 10 repressed IL-1 β secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis. Graphical
研究领域:
药用植物化学
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免疫学
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药物开发
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PubMed
高影响因子
危险品化学品经营许可证（带存储）