Journal of Hepatocellular Carcinoma
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2025
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IF 3.4
Jiayuan Zhang,Tian Tian,Shanshan Tian,Jinhai Yao,Yingwan Zhang,Rujia Xie,Ting Yang,Bing Han
Purpose This study aims to investigate the mechanism of action of arsenic-based agents against hepatocellular carcinoma (HCC) and to identify effective drug targets for HCC treatment.Methods Huh7 and HepG2 cells treated with NaAsO2 were assessed for cell viability, pyroptosis, migration, and invasion after undergoing lentiviral transfection. An orthotopic liver tumor model was established and divided into a model group and a treatment group. Proteins associated with QRICH1, PRMT1, cGAS-STING, and the classical pyroptosis pathway were quantified using Western blotting. The intracellular expression and localization of PRMT1 and NLRP3 in HCC were analyzed through cellular immunofluorescence. Co-immunoprecipitation (Co-IP) was performed to examine the protein interactions between PRMT1 and cGAS, as well as between STING and NLRP3. Chromatin immunoprecipitation (ChIP) was used to confirm QRICH1 enrichment in the PRMT1 promoter region.Results NaAsO2 treatment significantly inhibited the proliferation of Huh7 and HepG2 cells and effectively blocked their migration and invasion capabilities, while promoting cellular pyroptosis. Quantitative polymerase chain reaction(QRCR) and ChIP assays confirmed that NaAsO2 regulates PRMT1 expression by down-regulate QRICH1 binding in the PRMT1 promoter region. Additionally, NaAsO2 decreased the expression of the QRICH1-PRMT1 complex and upregulated the cGAS-STING signaling pathway, activating the downstream NLRP3-dependent classical pyroptosis pathway. Overexpression of QRICH1 reversed these effects.Conclusion NaAsO2 inhibits the expression of the QRICH1-PRMT1 axis, activates cGAS-STING signaling pathway transduction, and induces pyroptosis in HCC cells, thereby increasing the infiltration of immune cells in liver cancer tissues.
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Acta Pharmaceutica Sinica B
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2025
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IF 14.6
Xing Zhao,Xi Wu,Ranran Shang,Haitao Dou,Huachao Chen,Ninghua Tan
Pyroptosis is a unique programmed cell death pattern, and targeting it is an effective strategy against cancer therapy by overcoming apoptosis resistance. However, Golgi apparatus-targeted aggregation induced emission (AIE) photosensitizer as pyroptosis inducer for efficient antitumor treatment has not been reported. In this study, we successfully synthesized three new AIEgens, including TMN, TBN and TCN, by changing functional groups through a reasonable molecular design strategy, which targeted mitochondria, lysosome and Golgi apparatus (GA), respectively. In vitro experiments demonstrated that TCN exhibited the strongest reactive oxygen species (ROS) production ability and significant phototoxicity. Therefore, TCN as the GA-targeted AIE photosensitizer wore biomimetic hybrid extracellular vesicles (EVs) and M1-type macrophage membranes (denoted as EM@TCN) as pyroptosis inducer were rationally designed and engineered to trigger the production of GA cytotoxic ROS in situ . EM@TCN plus white light irradiation caused GA oxidative stress and induced pyroptosis synergistic photoimmunotherapeutic, which could rebuild tumor microenvironment and improve tumor immunogenicity. Combined with α PD-L1 (anti-mouse PD-L1 antibody), the biomimetic hybrid delivery system EM@TCN significantly inhibit the both primary and distant tumors, and effectively suppress the orthotopic breast tumor. This is the first report on a hybrid nanovesicle coated GA-targeted AIE photosensitizer to induce pyroptosis for combination with α PD-L1 to enhance antitumor photoimmunotherapy.
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2025
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IF 4
Minna Qiu,Zhiyu Hao,Yuhao Liu,Yuhang Liu,Minghang Chang,Xu Lin,Xiumei Liu,Na Dong,Wei Sun,Xiaohua Teng
Chlorpyrifos (CPF), a toxic organophosphorus insecticide, is widely used in agriculture to protect crops (eg., maize) from pests. The use of CPF in crops can result in accumulation in crop seeds, such as corn seeds, which is a primary feed ingredient in pigs. Pigs in China, which is an important source of animal-derived protein in the Chinese diet, account for over 50 % of the raised pig population in the whole world. Therefore, CPF may pose a potential risk to the health of non-target organisms (pigs and humans) through the food chain. However, whether CPF can damage porcine intestine remains unknown. Selenium (Se), an essential trace element, was reported to have antioxidant and anti-toxic effects. Tight junction (TJ) is an important mechanism of intestinal injury and pyroptosis is a new hotspot in the field of toxicology. Hence, we wanted to investigate whether CPF can damage pig intestine and whether selenium nanoparticles (SeNPs) supplement can alleviate CPF-induced pig intestine damage, and to study corresponding mechanism from the three aspects of OS, pytoptosis, and TJ. We established a model of SeNPs alleviating damage caused by CPF in intestinal porcine enterocytes (IPEC-J2 cells), and found that SeNPs alleviated CPF-induced oxidative stress (OS), pyroptosis, and intestinal barrier dysfunction in IPEC-J2 cells. Interestingly, OS, pyroptosis, and intestinal barrier dysfunction had serial relations, and ROS/Nrf2/Caspase-1/Occludin and ROS/Nrf2/Caspase-1/ZO-1 pathways played a role. Notably, ROS and Caspase-1 played an initial and important role, respectively. Our study added new information on pesticides-caused damage to non-target organisms, and provided new idea, insight, and targets to mitigatie pesticides-induced toxic effect on non-target organisms.
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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2022
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IF 5.756
Tao Wei,Zhiwei Zheng,Xiaoyan Wei,Yugang Liu,Wentao Li,Bingqing Fang,Di Yun,Zhaojun Dong,Baozhu Yi,Wulan Li,Xiaoping Wu,Dezhi Chen,Liping Chen,Jianzhang Wu
Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to β-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2′E)-3,3′-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics.
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Chemical Biology & Drug Design
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2024
·Vol. 103
·期 4
·e14522
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IF 3.2
Wanting Fu,Ziyuan Liu,Yingzhou Wang,Xindi Li,Xiang Yu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Pyroptosis is a programmed cell death process that frequently occurs in many diseases, including hyperuricemic nephropathy (HN). In HN, a range of stimuli mediates inflammation, leading to the activation of inflammasomes and the production of gasdermin D (GSDMD). Baicalin (BA), a natural flavonoid renowned for its antioxidant and anti-inflammatory properties, was investigated for its role in HN in this study. Initially, HN-like inflammation and pyroptosis were induced in HK-2 cells with treatment of monosodium urate (MSU), followed by the BA treatment. The expression of pyroptosis-associated genes, Panx-1 and P2X7, at both mRNA and protein levels was assessed through real-time polymerase chain reaction (RT-qPCR) and Western blotting (WB) without or with BA treatment. The results showed that expression of Panx-1 and P2X7 at mRNA and protein levels was increased in MSU-treated HK-2 cells, which subsequently decreased upon the BA treatment. Further experiments showed that BA could combine NLRP3 inflammasome and GSDMD, destabilizing GSDMD protein. Moreover, BA protected the cell membrane from MSU-induced damage, as evidenced by Hoechst 33342 and PI double staining, lactate dehydrogenase (LDH) assays, and electron microscopy observations. These results suggest that BA is involved in the regulating Panx-1/P2X7 pathways and thus inhibits pyroptosis, highlighting its potential therapeutic effect for HN.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Tingting Li,Yuanqing Huo,Huifang Ji,Wenjie Yan,Mengni Jia,Changming Xiong,Yunlan Li,Ruiping Zhang
Liver fibrosis, a pivotal pathological stage in the progression of chronic liver diseases to cirrhosis and hepatocellular carcinoma is characterized by liver sinusoidal endothelial cell (LSEC) capillarization, oxidative stress imbalance, and cell pyroptosis. Current clinical interventions show limited efficacy in reversing fibrosis, highlighting the urgent need for novel therapeutic strategies. In this study, we developed an L-arginine-loaded melanin-like nanozyme (L-Arg@MeNPs) that targets liver fibrosis through a triple-action mechanism: (1) sustained nitric oxiderelease from L-Arg restores LSEC fenestration, improving sinusoidal permeability; (2) the MeNPs exhibit catalase/superoxide dismutase-mimicking activity to scavenge reactive oxygen species, thereby blocking the NOD-like receptor pyrin domain-containing 3/caspase-1-mediated pyroptosis pathway; and (3) intrinsic photoacoustic/magnetic resonance dual-modal imaging enables real-time therapeutic monitoring. Overcoming the biosafety limitations of conventional metal-based nanozymes, this system demonstrates superior pH stability and metabolic degradability. In vivo studies confirm that L-Arg@MeNPs effectively ameliorate the fibrotic microenvironment and reduce excessive extracellular matrixdeposition, offering a targeted, safe, and theranostic solution for clinical liver fibrosis treatment.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2025
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IF 4.9
Heng Zhou,Yueming Long,Fangmei Yu,Chenhui Ji,Li Gui,Yunxia Lu
Resveratrol (RSV) ameliorates endothelial dysfunction (ED) primarily through sirtuin 1 (SIRT1). Increasing evidence shows pyroptosis as a novel mechanism in palmitic acid (PA)-induced ED. p66Shc is an adaptor protein involved in oxidative stress. However, whether RSV attenuates the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome via p66Shc remains elusive. This study aims to evaluate whether the anti-pyroptotic effect of RSV and the SIRT1 inhibitor EX527 are related to p66Shc. High-fat diet (HFD) induced obesity in mice, and RSV was administered intragastrically with 400mg/kg/d for 22 successive weeks. The serum levels of interleukin-1β (IL-1β) and IL-18 were analyzed, and the expression of related proteins were assayed with immunohistochemistry in the thoracic aorta. human umbilical vein endothelial cells (HUVECs) were induced by PA, then treated with RSV and EX527 respectively, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP) and expression of p66Shc, NLRP3, GSDMD and pyroptosis-related genes were assayed. RSV administration ameliorated endothelial cell pyroptosis by decreasing serum IL-1β and IL-18, the expression of NLRP3, p66Shc, and gasdermin D (GSDMD), and increasing the expression of SIRT1 in the HFD-treated thoracic aorta. PA promoted GSDMD-mediated endothelial cell pyroptosis by ROS production, LDH release, decreased MMP and SIRT1 expression, increased expression of p66Shc and activation of the NLRP3 inflammasome in a dose-dependent manner. RSV attenuated PA-induced pyroptosis, whereas EX527 reversed the antipyroptotic effect of RSV in PA-treated HUVECs. Our results suggested a new mechanism that RSV improves PA-induced pyroptosis in endothelial cells via the SIRT1-p66Shc-NLRP3 pathway.
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Journal of Functional Foods
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2025
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IF 4
Yancen Liu,Chuang Ma,Jinlong Tian,Bin Li,Jin Zhao
Malvacin-3- O -galactoside (M3G) is the most abundant anthocyanins component in blueberries and has high biological activity. We investigated the effect of a pulsed electric field (PEF) on the interaction between whey protein (WP) and M3G. Stability experiments showed that PEF significantly improved stability of the anthocyanin-whey protein complex (M3G-WP), particularly at 15 kV/cm for 30 min. PEF-treated M3G-WP (PEF-M3G-WP) was used as a model of silica-induced lung fibrosis to investigate its anti-inflammatory activity and molecular mechanisms. Both in vivo and in vitro experiments demonstrated that PEF-M3G-WP alleviated inflammation in macrophages. It upregulated the expression of PINK1 and Parkin and downregulated the expression of NLRP3, CASP1, and GSDMD NT. Furthermore, qPCR experiments showed that PEF-M3G-WP inhibited the release of inflammatory factors IL1b and IL18 by upregulating Atg5 and downregulating P62 in alveolar macrophage cell lines (MH-S). In summary, PEF-treated M3G-WP may be a potential method for alleviating pulmonary fibrosis.
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Cells
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2024
·Vol. 13
·期 24
·2070
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IF 5.1
Wei-Jian Nong,Xin-Yi Tong,Jian-Ming Ouyang
Endoplasmic reticulum stress (ERS) can activate pyroptosis through CHOP and TXNIP; however, the correlation between this process and the formation of kidney stones has not been reported. The purpose is to investigate the effects of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) on ERS and pyroptosis in HK-2 cells and to explore the formation mechanism of calcium oxalate stones. HK-2 cells were injured by 3 μm COM and COD. COM and COD significantly upregulated the expression levels of GRP78, CHOP, TXNIP, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD-N, and IL-1β). Fluorescence colocalization revealed that COM induced pyroptosis by inducing the interaction between TXNIP and NLRP3. Both COM and COD crystals can induce ERS and pyroptosis in HK-2 cells. COM induces the interaction with NLRP3 by the upregulation of CHOP and TXNIP and then promotes pyroptosis, while COD only promotes pyroptosis by the upregulation of CHOP. The cytotoxicity and the ability of COM to promote crystal adhesion and aggregation are higher than COD, suggesting that COM is more dangerous for calcium oxalate kidney stone formation.
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Antioxidants
·
2026
·Vol. 15
·期 5
·649
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IF 8.2
Jue Yang,Peng Zhao,Lianghong Zhou,Hui Song,Zili Feng,Hongjian Cui,Yanmei Li,Jianfei Qiu,Xiaojiang Hao
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited targeted therapeutic options, underscoring the urgent need for novel treatment strategies. Feilike (FLK), a Traditional Chinese Medicine formula with heat-clearing and detoxifying properties, aligns with key pathological features implicated in breast cancer progression. In addition, several of its components have demonstrated anti-tumor activity, positioning FLK as a potential therapeutic candidate for TNBC. In this study, we employed an integrated approach combining network pharmacology, transcriptomic analysis, and experimental validation to investigate the anti-TNBC effects of FLK. Our results demonstrate that FLK significantly inhibits the proliferation of TNBC cell lines and patient-derived organoids and induces typical pyroptotic features, including cell swelling and increased lactate dehydrogenase (LDH) release. Mechanistically, FLK triggers a mutant p53 signaling cascade involving calcium dysregulation, endoplasmic reticulum stress (ERS) activation, mitochondrial dysfunction, and reactive oxygen species (ROS) accumulation, which collectively activate the P38/JNK–Caspase-3/GSDME pathway to induce pyroptosis. In vivo, FLK markedly suppresses tumor growth in a 4T1 orthotopic mouse model and enhances the anti-tumor efficacy of Cyclophosphamide. Furthermore, Licochalcone B (LCB) is identified as a key bioactive constituent that recapitulates the pyroptosis-inducing effects of FLK. Collectively, our findings uncover a previously unrecognized mutant p53–ERS–ROS–MAPK signaling axis underlying FLK-induced pyroptosis and provide mechanistic insight and experimental evidence supporting the repurposing of FLK as a potential therapeutic strategy for TNBC.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Lei Diao,Yang Ma,Liping Wang,Peng Li,Bin Zhang,Weijing Meng,Jingzeng Cai,Yan Meng,Yuxun Zhou,Jingying Zhai,Huijie Chen
Thiacloprid (THI) is a synthetic insecticide, the misuse is targeted chiefly to control aphid pest species in orchards and vegetables. Melatonin (MET) is a hormone that plays crucial physiological roles in anti-inflammatory capacities of fish. We explored the function of MET (100 μM) to mitigate the toxicity induced by THI (20 μM) in lymphocytes. Our results indicate that THI led to a notable rise in lymphocyte mortality. Lymphocytes exposed to THI exhibited a heightened incidence of pyroptosis, accompanied by upregulation in expression associated with pyroptosis (NLRP3, GSDMEA, and IL-18). Meanwhile, THI exposure led to a decrease in lymphocyte mitochondrial membrane potential, an increase in mtROS levels, and a reduction in intracellular ATP, DNA, and NADPH/NADP+ levels, indicating an imbalance in the mitochondrial metabolism within the lymphocytes. Additionally, these effects were reversed by MET treatment, where MitoQ treatment showed that the suppression of mtROS reduced the lymphocyte pyroptosis caused by THI via the mtROS/cGAS-STING/NF-κB axis. Importantly, MET provided defense against the immunotoxic impacts of THI by ameliorating pyroptosis and enhancing anti-inflammatory capability via the mtROS/cGAS-STING/NF-κB axis. Our research potentiates the safeguarding of cultured fish from biological hazards caused by THI and highlights the valuable application of MET in common carp.
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