Balkan Medical Journal
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2026
·Vol. 43
·期 5
·253
·
IF 4.5
Ke Xu,Xiangyu Ren,Hongjie Cao,Tiantian Lyu,Zuisu Yang,Fangfang Huang
Background Bisphenol A (BPA), a widely used industrial chemical, is a well-known endocrine disruptor linked to testicular damage and impaired male reproductive function. Fucoxanthin (Fx), a marine carotenoid with potent antioxidant properties, has not been extensively studied for its potential to mitigate BPA-induced testicular injury. Aims To evaluate the protective effects of Fx against BPA-induced testicular injury and explored the underlying signaling mechanisms. Study Design Experimental study. Methods A mouse model of BPA-induced testicular injury was established. Transcriptomic analysis was performed to identify significantly altered genes. The therapeutic potential of Fx was assessed using combined molecular and histological approaches. Complementary in vitro experiments with TM3 Leydig cells were conducted to support the in vivo findings. Results Fx administration markedly attenuated BPA-induced disruptions in serum sex hormones, testicular histopathology, and proinflammatory cytokine levels. Ribonucleic acid sequencing revealed that Fx’s protective effects are associated with modulation of the nuclear factor kappa B (NF-κB), nucleotide-binding oligomerization domain-like, and Toll-like receptor signaling pathways. Validation experiments indicated that Fx inhibits nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and suppresses pyroptosis, accompanied by downregulation of key genes and proteins in the lipopolysaccharide/NLRP3 signaling cascade. In vitro analyses confirmed that Fx reduces oxidative stress and inflammation by inhibiting NF-κB activation and pyroptosis. Conclusion These findings suggest that Fx may serve as a promising dietary supplement or nutraceutical agent to mitigate the adverse reproductive effects of environmental endocrine disruptors, with potential benefits for male reproductive health.
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Qiushi Li,Zhen Yang,Nana Feng,Jian Xiao,Qingqing Huang,Biyu Zhou,Jie Hao,Ming Gao,Zhanzhan Zhang,Yang Liu
Pyroptosis is a highly immunogenic form of programmed cell death with great potential for cancer immunotherapy. However, achieving tumor-selective and intrinsically controllable induction of pyroptosis remains challenging. Here, we report a nanoparticle-based mitochondrial disruptor, termed nanoMd/PA, which acts as an intrinsic pyroptosis inducer by directly destabilizing mitochondrial membranes in tumor cells. Inspired by the membranolytic activity of antimicrobial peptides, nanoMd/PA is engineered with a guanidinium-rich shell that selectively accumulates in tumor mitochondria and disrupts membrane integrity through a pore-forming mechanism, thereby initiating gasdermin-mediated pyroptosis. The nanoparticle is further shielded with a pH-responsive polymer layer that remains inert during circulation but activates its mitochondrial-lytic function specifically within the acidic tumor microenvironment. In an orthotopic colorectal cancer model, nanoMd/PA treatment triggers robust pyroptosis, resulting in significant tumor suppression, extended survival, and potent inhibition of metastatic spread, all without detectable systemic toxicity. This work establishes a carrier-independent, nanomaterial-driven approach to induce pyroptosis through direct mitochondrial membrane disruption, offering a new paradigm for activating antitumor immunity with synthetic, intrinsically immunomodulatory nanoparticles.
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高影响因子
ACS Nano
·
2026
·
IF 17.3
Wen-Da Wang,Chi-Hui Yang,Wen-Tao Mo,Su-Ran Li,Qi-Chao Yang,Jun Xie,Yun-Hong Zhong,Junjie Zhang,Cong-Fa Huang,Wei-Wei Deng,Xian-Zheng Zhang,Zhi-Jun Sun
The intravenous delivery of oncolytic viruses (OVs) often demonstrates limited therapeutic efficacy due to rapid clearance by peripheral neutralizing antibodies and poor penetration into deeper tumor regions. To overcome these bottlenecks, we report a triple-cascade responsive pneumatic nanomotor (HLNO) designed for systemic delivery of the oncolytic herpes simplex virus (oHSV). The HLNO nanomotor utilizes a hierarchically structured core–shell design featuring an oHSV core encapsulated within a glutathione-responsive liposome layer and hyaluronic acid outer shell while incorporating the pH-sensitive nitric oxide (NO) donor. This system enables immune evasion of oHSV in peripheral circulation while demonstrating programmable activation that specifically responds to tumor microenvironment stimuli. It is noteworthy that the HLNO nanomotor utilizes NO-propelled active motion under acidic conditions to enhance extravasation and tissue deep penetration, followed by hyaluronidase-mediated deshielding and glutathione-triggered oHSV release. Then, the HLNO nanomotor activates the caspase-3/GSDME pathway to induce immunogenic pyroptosis, which enhances antitumor immunity by increasing CD8+ T cell infiltration and M1-like macrophage polarization while driving vascular normalization and alleviating tumor hypoxia. By integrating immune shielding with cascade-responsive release, this platform addresses key limitations of systemic OVs delivery, offering an approach to enhance immunotherapy efficacy in immunologically “cold” tumors.
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CHEMICO-BIOLOGICAL INTERACTIONS
·
2026
·
IF 5.2
Xin-Yi Tong,Wei-Jian Nong,Zhang Jia-Yi,Jian-Ming Ouyang
Current research on magnesium ammonium phosphate hexahydrate (MAP) stones has focused exclusively on MAP crystal formation, while the mechanisms by which MAP crystals damage macrophages and contribute to stone formation remain unreported. Given the prevalence of urinary tract inflammation and cellular injury in MAP stone patients, and the pivotal role of macrophages in inflammation, this study investigated the interaction between MAP crystals and macrophages, as well as their potential effects on MAP stone formation. MAP crystals (≈4 μm) were synthesized, characterized, and their interaction with macrophages, cytotoxicity, and expression of key proteins in the caspase-1-mediated pyroptosis pathway were detected. Results showed MAP crystals had significant cytotoxicity. Besides canonical endocytosis and adhesion, they induced macrophage extracellular traps (METs), a newly identified interaction between MAP crystals and macrophages. MAP crystals also triggered massive migrasome production to exacerbate local inflammation (not observed in MAP-saturated solution) and induced more pronounced macrophage pyroptosis than MAP solution. In conclusion, MAP crystals induce METs formation, migrasome production, and pyroptosis in macrophages, impairing the macrophage biomembrane system and exacerbating inflammation, thereby increasing stone formation risk, providing a scientific basis for elucidating MAP stone formation mechanisms.
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PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·1-24
·
IF 12.6
Tong Xin-Yi,Nong Wei-Jian,Tan Run-Min,Ouyang Jian-Ming
Objective This study aimed to compare the differences in pyroptosis and polarization of macrophages induced by different sizes of calcium oxalate monohydrate (COM) crystals and discuss the mechanism of kidney stone formation. Methods COM crystals with sizes of about 100 nm, 500 nm, 2.5 μm, and 10 μm were synthesized and characterized. THP-1 cells were induced to differentiate into macrophage-like cells. The damage of COM crystals to Mφs was evaluated by CCK-8 assay. The activation of the pyroptosis signaling pathway, cell morphology, and proportion of pyroptosis cells in Mφs induced by COM crystals were detected. Finally, the proportion of M1/M2 polarization was qualitatively and quantitatively assessed. Results COM-100 nm, COM-500 nm, COM-2.5 μm, and COM-10 μm all significantly induced the pyroptosis and polarization of Mφs. Among them, at the same cell viability, COM-10 μm induced the highest pyroptosis rate. The expression of NLRP3 and GSDMD-N induced by COM-10 μm increased by 81.43 ± 11.45% and 112.00 ± 9.87%, respectively, and the rate of caspase-1/PI double-positive pyroptosis cells was 22.2%. Meanwhile, COM-10 μm induced the highest proportion of M1 polarization (M1/M2 ratio was 209.90% ± 2.54%). Conclusion COM-10 μm significantly activates the classical caspase-1-mediated pyroptosis pathway and promotes M1 polarization in Mφs. Therefore, at the same cell viability, large-sized micro-COM is more capable of inducing inflammation than nano-COM. Graphical
研究领域:
纳米技术
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泌尿科学
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免疫学
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细胞生物学
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材料科学
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高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 10
·1-10
·
IF 8.1
Li Ming-Qiao,He Yu-Qi,Zhang Meng-Ni,Tang Wan,Tan Ya,Cheng Yue,Yang Mei,Zhao Nan,Li Ling,Yu Si-Rui,Li Ruo-Lan,Pan Qiong,Wu Ming-Yue,Chai Jin
Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Anjun Song,Wenjie Wang,Huan Wang,Yanjun Ji,Yanjie Zhang,Jinsong Ren,Xiaogang Qu
Pyroptosis has garnered increasing attention because of its ability to trigger robust antitumor immunity. Pyroptosis is initiated by the activation of inflammasomes, which are regulated by various organelles. The collaboration among organelles offers several protective mechanisms to prevent activation of the inflammasome, thereby limiting the induction of efficient pyroptosis. Herein, a multiorganelle homeostasis disruptor (denoted BLL) is constructed by encapsulating liposomes and bortezomib (BTZ) within a layered double hydroxide (LDH) nanocage to continuously activate inflammasomes for inducing efficient pyroptosis. In lysosomes, the negatively charged liposomes are released to recruit the NLRP3 inflammasomes through electrostatic interactions. ER stress is induced by BTZ to enhance the activation of the NLRP3 inflammasome. Meanwhile, the BLL nanocage exhibited H+-scavenging ability due to the weak alkalinity of LDH, thus disrupting the homeostasis of the lysosome and alleviating the degradation of the NLRP3 inflammasome by lysosomal-associated autophagy. Our results suggest that the BLL nanocage induces homeostatic imbalance in various organelles and efficient pyroptosis. We hope this work can provide new insights into the design of an efficient pyroptosis inducer by disrupting the homeostatic balance of multiple organelles and promote the development of novel antineoplastic platforms.
研究领域:
癌症研究
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免疫学
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纳米技术
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细胞生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Hao Zhang,Jia-Gen Cui,Ming-Shan Chen,Jia-Xin Wang,Xiao-Han Sun,Yi Zhao,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP), which is widely used in agricultural plastics, accumulates in humans and animals through the food chain over time, resulting in liver toxicity. Recent studies have reported that pyroptosis and mitochondrial damage are closely related to a variety of liver diseases, but the specific mechanism is still unclear. To address this issue, in vitro and in vivo hepatotoxicity models were established. The results demonstrated that exposure to DEHP caused a buildup of MEHP in livers, altered liver metabolite composition, and caused pyroptosis-like changes in hepatocytes. After DEHP treatment, REDOX homeostasis was unbalanced, and mitochondrial reactive oxygen species (mtROS) were overproduced. MEHP exposure activates pyroptosis mediated by TNF/TNFR1 signaling and upregulates the perforating protein GSDMD-N to destroy the mitochondrial membrane of hepatocytes. Above all, this study elucidates the potential involvement of TNF/TNFR1 signaling-mediated pyroptosis in mitochondrial damage and confirms that the regulation of pyroptosis is helpful in maintaining normal mitochondrial function.
研究领域:
毒理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Liu-Gen Cui,Miao-Miao Zhai,Jian-Jian Yin,Zhi-Mo Wang,Shu-Hui Wang,Yue-Jiao Zhou,Pei-Pei Li,Yang Wang,Li Xia,Pei Wang,Xue-Xiang Cha,Li-Rong Zhang,Sheng-Na Han
Several studies have associated the epitranscriptomic RNA modification of N6-methyladenosine (m 6 A) with cardiovascular diseases; however, how m 6 A modification affects cardiomyocyte pyroptosis after myocardial infarction (MI) remains unknown. Here, we showed that AlkB homolog 5 (ALKBH5), an m 6 A demethylase, is crucial in cardiomyocyte pyroptosis after MI. We used MI rat and mouse models, a cell hypoxia model of rat primary cardiomyocytes (RCMs), and rat embryonic ventricle cell line (H9c2) to explore the functional role of m 6 A modification and ALKBH5 in the heart and cardiomyocytes. Using plasmids and small interfering RNAs, the expressions of ALKBH5 and NOD-like receptor family pyrin domain-containing 3 (NLRP3) were determined to study their functions in regulating cardiomyocyte m 6 A and pyroptosis, respectively. We characterized the role of ALKBH5, which exhibited elevated expression in the ischemic heart tissue of rats and mice and hypoxic cardiomyocytes (RCMs and H9c2 cells). ALKBH5 knockdown alleviated hypoxia-induced H9c2 cell pyroptosis by inhibiting NLRP3 inflammasome activation, whereas ALKBH5 overexpression had the opposite effect. NLRP3 knockdown alleviated hypoxia-induced H9c2 cardiomyocyte pyroptosis by inhibiting ALKBH5 expression, whereas NLRP3 overexpression had the opposite effect. Mechanistically, ALKBH5 mediated m 6 A modification of NLRP3 mRNA in an IGF2BP2-dependent manner, and NLRP3, as a nuclear transcription factor, regulated the ALKBH5 transcription process. Targeting the ALKBH5-NLRP3 loop with the small-molecule inhibitors alleviated cardiomyocyte pyroptosis. Our results highlight that ALKBH5-NLRP3 forms a positive feedback loop that promotes cardiomyocyte pyroptosis after MI. Therefore, inhibiting the ALKBH5-NLRP3 loop is a potential strategy for treating cardiovascular diseases.
研究领域:
心血管疾病
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表观转录组学
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分子生物学
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PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xiujie Zhao,Yan Ma,Jianhao Di,Yanqi Qiao,Jie Yu,Yongmei Yin,Rimo Xi,Meng Meng
Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12 was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).
研究领域:
肿瘤学
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免疫学
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药理学
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PubMed
高影响因子
JOURNAL OF MEDICINAL FOOD
·
2024
·
IF 1.7
Ruixi Luo,Yudie Hu,La Wang,Wenjia Wang,Ping Wang,Zunli Ke,Didong Lou,Weiyi Tian
It is currently thought that excess fatty acid-induced lipotoxicity in hepatocytes is a critical initiator in the development of nonalcoholic fatty liver disease (NAFLD). Lipotoxicity can induce hepatocyte death; thus, reducing lipotoxicity is one of the most effective therapeutic methods to combat NAFLD. Abundant evidence has shown that hesperidin (HSP), a type of flavanone mainly found in citrus fruits, is able to ameliorate NAFLD, but the molecular mechanisms are unclear. We previously reported that pyroptosis contributed to NAFLD development and that inhibiting pyroptosis contributed to blunting the progression of NAFLD in rat models. Therefore, we questioned whether HSP could contribute to ameliorating NAFLD by modulating pyroptosis. In this study, a high-fat diet (HFD) induced dyslipidemia and hepatic lipotoxicity in rats, and HSP supplementation ameliorated dyslipidemia and insulin resistance. In addition, the HFD also caused pyroptosis in the liver and pancreas, while HSP supplementation ameliorated pyroptosis. In vitro, we found that HSP ameliorated palmitic acid-induced lipotoxicity and pyroptosis in HepG2 and INS-1E cells. In conclusion, we showed for the first time that HSP has a protective effect against liver and pancreas damage in terms of pyroptosis and provides a novel mechanism for the protective effects of HSP on NAFLD.
研究领域:
药理学
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营养学
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肝病学
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细胞生物学
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分子生物学
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PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Hongyuan Zhao,Xiaoyu Chen,Li Zhang,Fanqiang Meng,Libang Zhou,Zhaoxin Lu,Yingjian Lu
Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis, but the adverse effects of hyperuricemia on the liver have been seriously neglected. This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo . Cell free extracts of high dose L. rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1 % to 14.9 % by inhibiting NLRP3 recruitment, which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder. In purine dietary induced hyperuricemia (PDIH) mice model, liver oedema and pyroptosis were ameliorated after L. rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3, caspase-1 and gasdermin-D from 1.61 to 0.86, 3.15 to 1.01 and 5.63 to 2.02, respectively. L. rhamnosus Fmb14 administration restored mitochondrial inner membrane protein (MPV17) and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice, indicating that dysbiosis of mitochondrial membrane potential was restored in liver. Intriguingly, PDIH pyroptosis stimulates the process of apoptosis, which leads to severe leakage of hepatocytes, and both of pyroptosis and apoptosis were decreased after L. rhamnosus Fmb14 treatment. Therefore, L. rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.
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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药理学
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病理学
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高影响因子
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