NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2025
·
IF 3.1
You Xujun,Li Honghan,Li Qixin,Zhang Qing,Cao Yiguo,Fu Wei,Wang Bin
Prostate cancer (PCa) is an epithelial malignancy affecting the prostate gland. Astragaloside IV combined with polypeptide extract from scorpion venom (PESV) has been reported to inhibit the growth of PCa. This study aimed to investigate the mechanisms by which this combination mitigates the progression of PCa. Bioinformatic analysis was utilized to investigate the correlation between zinc finger DHHC-type containing 1 (ZDHHC1) expression and PCa progression. The extent of pyroptosis in PCa cells was assessed by measuring cell viability, IL-1β and IL-18 secretion, LDH release, and HMGB1 content. PCa mouse models were constructed by subcutaneous injection of DU145 or PC-3 cells into nude mice, with subsequent monitoring of tumor weight and volume. ZDHHC1 expression was significantly lower in PCa patient tissues, which correlated with a poor prognosis. ZDHHC1 overexpression inhibited PC-3 and DU145 cell viability and increased IL-1β, IL-18, LDH, and HMGB1 levels in cell supernatants. Notably, the pyroptosis inhibitor LDC7559 partially reversed these effects. Co-IP assay demonstrated an interaction between ZDHHC1 and GSDMD. ZDHHC1 overexpression significantly enhanced GSDMD palmitoylation-mediated membrane translocation and pyroptosis; however, this effect was partially reversed by the palmitoylation inhibitor 2-BP. The combination of Astragaloside IV and PESV promoted GSDMD membrane translocation and pyroptosis in PCa cells, with ZDHHC1 knockdown partially reversing the effects of Astragaloside IV-PESV. Furthermore, treatment with Astragaloside IV-PESV significantly inhibited tumor tissue growth in tumor-bearing nude mouse models. Astragaloside IV-PESV enhances palmitoylation-mediated membrane translocation of GSDMD-N by upregulating ZDHHC1 expression, thereby facilitating pyroptosis in PCa cells and attenuating PCa progression.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
·
IF 12.6
Yang Ningning,Hua Rongrong,Lai Yingying,Zhu Peijun,Ding Jian,Ma Xianhui,Yu Gaoxiang,Xia Yiheng,Liang Chao,Gao Weiyang,Wang Zhouguang,Zhang Hongyu,Yang Liangliang,Zhou Kailiang,Ge Lu
In the field of large-area trauma flap transplantation, preventing avascular necrosis remains a critical challenge. Key mechanisms for improving flap viability include angiogenesis promotion, oxidative stress inhibition, and cell death prevention. Recently, two-dimensional ultrathin Ti 3 C 2 T X (MXene) nanosheets have gained attention for their potential contributions to these processes, though MXene’s physiological impact on flap survival had not been previously investigated. This study is the first to confirm MXene's biological effects on the ischaemic microenvironment post-skin flap transplantation. Findings indicated that MXene significantly decreased the necrotic area in ischaemic flaps (37.96% ± 2.00%), with reductions of 30.40% ± 1.86% at 1 mg/mL and 20.19% ± 2.11% at 2 mg/mL in a concentration-dependent manner. Mechanistically, MXene facilitated in situ angiogenesis, mitigated oxidative stress, suppressed pro-inflammatory pyroptosis, and activated the PI3K-Akt pathway, particularly influencing vascular endothelial cells. Comparative transcriptome analysis of skin tissues with and without MXene treatment provided additional evidence, highlighting mechanisms such as pro-inflammatory pyroptosis, ROS metabolic processes, endothelial cell proliferation regulation, and PI3K-Akt signaling pathway activation. Overall, MXene demonstrated biological activity, effectively promoting ischaemic flaps survival and presenting a novel strategy for addressing ischaemic necrosis in skin flaps. Graphical abstract
研究领域:
医学
·
生物材料学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
·
2024
·Vol. 92
·期 1
·e13893
·
IF 2.5
Yongmei Peng,Yanan Xu,Sainan Li,Mingkun Shao,Zijia Shen,Wenjin Qi
Problem Vulvovaginal candidiasis (VVC) is a common mucosal fungal infection, and Candida albicans is the main causative agent. The NLRP3 inflammasome plays an important role in VVC, but the underlying mechanism is unknown. Method of Study Vaginal epithelial cells were divided into three groups: control, C. albicans strain SC5314 (wild-type, WT), and WT+ Matt Cooper Compound 950 (MCC950, a specific NLRP3 inhibitor). After human vaginal epithelial cells were pretreated with 1 µmol/L MCC950 for 2 h, C. albicans (MOI = 1) was cocultured with the human vaginal epithelial cells for 12 h. The cell supernatants were collected, LDH was detected, and the IL-1β and IL-18 levels were determined by ELISA. The expression of the pyroptosis-related proteins NLRP3, Caspase-1 p20 and GSDMD was measured by Western blotting analysis. The protein expression of the pyroptosis-related N-terminus of GSDMD (GSDMD-N) was detected by immunofluorescence. Results In this study, we showed that the WT C. albicans strain induced pyroptosis in vaginal epithelial cells, as indicated by the LDH and proinflammatory cytokine levels and the upregulated levels of the pyroptosis-related proteins NLRP3, Caspase-1 p20, and GSDMD-N. MCC950 reversed the changes in the expression of these proteins and proinflammatory cytokines in vaginal epithelial cells. Conclusion C. albicans activated the NLRP3 inflammasome to induce vaginal epithelial cell pyroptosis. MCC950 inhibited the NLRP3 inflammasome, reduced vaginal epithelial cell pyroptosis, and decreased the release of inflammatory cytokines.
研究领域:
微生物学
·
免疫学
·
细胞生物学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yukun Lin,Kunjing Liu,Jiahui Chen,Tingjie Li,Zijin Sun,Yifan Fan,Peng Zou,Yanting Liu,Chunyu Wang,Chongyang Ma,Xueqian Wang,Fang Lu,Fafeng Cheng,Changming Zhai
A B S T R A C T Ethnopharmacological relevance Pinellia ternata (Ban-xia) and Coptidis Rhizoma (Huang-lian) form a classic herb pair (BXHL) in traditional Chinese medicine that has demonstrated clinical efficacy against Helicobacter pylori ( H. pylori ) infection. However, its pharmacological mechanisms remain insufficiently defined. Aim of the study This study aimed to (1) evaluate the anti- H. pylori colonization effects of BXHL in vitro and in vivo; (2) elucidate its mechanism through the NLRP3-mediated pyroptosis pathway; and (3) assess its influence on gastrointestinal microbiota and identify potential active components. Materials and methods BXHL composition was characterized by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Anti- H. pylori activity was examined using GES-1 cell co-culture and infected mouse models. Gene expression and signaling pathways were analyzed by RNA-seq, ELISA, RT-qPCR, Western blotting and IHC. Histopathology, bacterial load assays, and ultrastructural observation assessed anti-colonization efficacy. Microbiota alterations were analyzed via 16S rRNA sequencing and molecular docking evaluated interactions between BXHL compounds and NLRP3 targets. Results BXHL significantly reduced H. pylori adhesion, colonization and restored NLRP3-mediated pyroptosis suppressed by infection. Transcriptomic and molecular analyses confirmed reactivation of the NLRP3 signaling cascade. BXHL preserved gut microbial diversity, unlike triple therapy, and exhibited moderate direct antibacterial effects. Conclusion BXHL inhibits H. pylori colonization through suppressing bacterial adhesion factors and activating NLRP3-mediated pyroptosis, while causing no disruption to the gut microbiota. These findings position BXHL as a safe and effective adjunctive therapy, which provides a novel strategy to improve H. pylori eradication that complements conventional antibiotics.
研究领域:
民族药理学
·
微生物学
·
中医中药
·
分子生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHYSICO-CHIMICA SINICA
·
2025
·
IF 13.5
Tiejin Chen,Xiaokuang Xue,Jian Li,Minhui Cui,Yongliang Hao,Mianqi Xue,Haihua Xiao,Jiechao Ge,Pengfei Wang
Photodynamic therapy (PDT), as a FDA-approved therapeutic modality, has witnessed substantial advancements in the field of oncology. However, the conventional PDT may suffer poor prognosis due to the transient nature of ROS, excessive phototoxicity, and inducing traditional apoptosis. In this study, a nanoengineered carbon dots (NCDs) was constructed through electrostatic interaction between a positive-charged carbon dots photosensitizers (PCDs) and new indocyanine green (IR820). The introduction of IR820 at variable ratios could change the surface charge and amphiphilic characteristics of NCDs, thereby modulating the membrane-anchoring capability of NCDs. Besides, the J-aggregation of IR820 led to a redshift of fluorescence from NIR-I to NIR-II region, thereby achieving NIR-II imaging. Furthermore, the photoactivity of PCDs was quenched by IR820, with subsequent restoration of PDT occurring contingent on the photobleaching of IR820 via 750 nm laser irradiation. Finally, both in vitro and in vivo studies had demonstrated that under a cascaded laser irradiation, the membrane-targeted NCDs could effectively induce cell pyroptosis, thereby eradicating tumors with minimal side effects while simultaneously activating immune responses to inhibit tumor lung metastasis. This study developed a multifunctional nanoengieering carbon dots and offered novel perspectives for tumor photodynamic-immunotherapy with enhanced controllability, improved efficacy and high security.
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2025
·Vol. 20
·期 6
·e0325189
·
IF 2.6
Yu Wang,Chaofan Chen,Yushan Li,Ran Li,Jinghan Wang,Chao Wu,Haonan Chen,Yingchao Shi,Shengfang Wang,Chuanyu Gao
Kaempferol exhibits various biological activities, including antioxidant and anti-inflammatory effects. Its role in modulating lipid metabolism and inhibiting inflammatory responses to suppress the progression of atherosclerosis has been confirmed. However, its impact on macrophage pyroptosis and the underlying mechanisms remain unclear. This study aims to investigate the effects of kaempferol (Kae) on lipopolysaccharide (LPS)-induced macrophage pyroptosis and its potential mechanisms. In the experiments, we used the CCK8 assay to evaluate cell viability, ROS detection kits to measure intracellular reactive oxygen species (ROS) levels, Western Blot to detect the expression of proteins such as NOD-like receptor family pyrin domain-containing 3 (NLRP3), nuclear factor erythroid 2-related factor 2 (NRF2), gasdermin D (GSDMD), and heme oxygenase-1 (HO-1), and immunofluorescence to observe NRF2 nuclear translocation. The results showed that kaempferol alleviated LPS-induced cell viability decline and lactate dehydrogenase (LDH) release, inhibited excessive ROS generation, and suppressed NLRP3 inflammasome activation by increasing glutathione (GSH) and HO-1 levels, thereby reducing the expression of inflammatory factors. Additionally, kaempferol promoted NRF2 nuclear translocation, and the application of the NRF2 inhibitor ML385 reversed its antioxidant and anti-inflammatory effects. In vivo experiments further confirmed that kaempferol inhibited oxidative stress and reduced macrophage pyroptosis by activating the NRF2 pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Shuge Shu,Xinting Chen,Jiawen Ren,Xiangyu Yu,Hao Zhang,Yongquan Yu
Glyphosate is reported to compromise the central nervous system and induce behavioral disorders in mammals. However, evidence is deficient with respect to the potential mechanisms involved. In this study, C57BL/6 mice were orally exposed to glyphosate at doses ranging from 0 to 200 mg/kg/day for 16 weeks. The results of behavioral tests showed that glyphosate decreased time spent and distance traveled within the central area of open field test, decreased the retention time and number of entries into the open arms, and increased the retention time and number of entries into the close arms of elevated plus maze test. The expressions of anxiety-related genes htr5 , htr6 , and tmem132d were also significantly upregulated by glyphosate. This behavioral phenotype was linked to the permeation of glyphosate into the brain via disrupting the functional tight junctions of blood–brain barrier (BBB). As a result, glyphosate directly compromised the morphological structure of neurons, increased the number of IBA-1 microglia, and activated the expression of NLRP3-mediated pyroptosis pathway (NLRP3, Caspase-1, GSDMD, and IL-18) in the hippocampus of mice. Moreover, the glyphosate-induced activation of NLRP3 pathway in microglia was markedly reversed by NLRP3 inhibitor MCC950. The conditional mediums from glyphosate-treated BV2 cells aggravated the cytotoxicity of HT-22 neurons, which was also rescued by MCC950. In conclusion, this work demonstrated that microglia-mediated activation of NLRP3 pyroptosis pathway plays a detrimental role in glyphosate-behavioral disorders and neuron damage. These findings provide novel evidence for glyphosate-induced neurotoxicity and support the growing association between glyphosate exposure and neurobehavioral disorders in humans.
研究领域:
神经科学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Li Xiaoyan,Wang Ying,Cao Xinyue,Song Xinran,Chen Liang,Chang Meiqi,Chen Yu,Huang Bingcang
Background Reactive oxygen species (ROS)-mediated pyroptosis provides a robust strategy for overcoming apoptosis resistance in breast cancer therapy. Nevertheless, the low efficiency of pyroptosis remains an undeniable challenge. Overcoming this obstacle necessitates the creation of innovative approaches and nanocatalysts to boost ROS generation. Herein, the distinct lanthanum-doped BiFeO 3 (La-BFO) piezoelectric nanozymes are rationally designed and engineered for the specific cell pyroptosis of breast cancer through inducing the amplified production of ROS and releasing La ions. Results The introduction of La reduces the recombination rate of electron-hole pairs through narrowing the bandgap and creating the oxygen vacancy of BFO, improving the harmful ROS generation efficiency. Importantly, the released La ions robustly disrupt the lysosomal membrane, ultimately inducing cell pyroptosis, in combination with ROS-induced biological effect. Conclusion In vitro and in vivo antineoplastic results confirm the desirable therapeutic effect on combating tumor. Especially, the iron and bismuth elemental components endow the nanocomposites with dual-mode computed tomography/magnetic resonance imaging ability, guaranteeing the potential therapeutic guidance and monitoring. Graphical
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Chengming Tian,Mengchi Sun,Zhichao Chen,Jiawei Shi,Chen Xu,Meng Niu,Jin Sun,Hongzan Sun
Treatment for triple-negative breast cancer (TNBC) is severely hampered by factors such as the lack of specific molecular targets and high tumor immunosuppression. Benefiting from the natural tumor-targeting properties of microbes, oncolytic bacteria-mediated antitumor therapy has shown great clinical potential in TNBC treatment but suffers from poor bioavailability and limited monotherapy efficacy. Herein, a coordination-guided therapeutic-coating strategy for oncolytic bacteria to synergistically enhance pyroptosis against is developed TNBC. By introducing calcium ions and the classical antitumor agent mitoxantrone (MTO) onto the surface of Salmonella typhimurium VNP20009, MTO@Ca-VNP20009 via intermolecular coordination interactions is constructed. The surface coating of VNP20009 reduces the immunogenicity of oncolytic bacteria during in vivo circulation. Given the tumor-targeting ability of VNP20009, MTO can be synchronously delivered to tumors. The responsive intratumoral release of MTO, in combination with VNP20009, potentiates tumor cell pyroptosis, triggering a robust immune response. Therapeutic outcomes demonstrate significantly inhibited orthotopic tumor growth and reduced distal and lung metastases in both subcutaneous and metastatic TNBC murine models. This intermolecular force-guided therapeutic-coating strategy holds significant potential for enhancing the bioavailability and therapeutic efficacy of oncolytic bacteriotherapy.
研究领域:
肿瘤学
·
微生物学
·
纳米医学
·
免疫治疗学
·
药理学
·
生物工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Linbang Wang,Rui Dou,Yunlong Ma,Jiayu Zhang,Xiaomeng Cai,Jinkun Liu,Xiaoguang Liu,Jun Chen
The immunosuppressive microenvironment (TME) of osteosarcoma (OS) results in an unsatisfactory conventional therapeutic effect. Conventional chemotherapy-induced apoptosis is unsuccessful to fully activate anti-tumor immunity as it fails to release Tumor-Associated Antigens (TAAs) and promotes efferocytosis of Tumor-Associated Macrophages (TAMs). In this study, we propose to remodel TME by inducing OS cells to immunogenic cell death, including pyroptosis and necroptosis induced by efferocytosis inhibition of TAMs. Specifically, we constructed a piezoelectric catalyst, BFO@CaO₂-TPP (BCT), which targets mitochondria. Under ultrasound, BCT generated reactive oxygen species (ROS) by enhancing the Fenton reaction and released Ca 2+ to trigger mitochondrial calcium overload, which synergistically activated the caspase-3/GSDME nonclassical pyroptosis pathway and prompted the release of proinflammatory molecules from tumor cells. At the same time, BCT disrupts mitochondrial oxidative phosphorylation (OXPHOS) in TAMs, inhibits their efferocytotic capacity. More importantly, TAMs facilitate the elevation of the GSDME express and TNF/TNFR1 interaction in osteosarcoma cells, favoring pyroptosis and necroptosis. Simultaneous endogenous and exogenous regulation is ultimately transforms the ‘cold’ TME into a ‘hot’ state. Patient-derived organoid-based validation confirmed the translational potential of this strategy.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
·
分子生物学
·
转化医学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
Pharmacognosy Magazine
·
2025
·
IF 0.9
Qing Liu,Ying Lan,Zhe Bai
BackgroundHyperoside is a potential liver cell and mitochondrial protector, but there is no evidence to suggest that hyperoside can effectively treat doxorubicin (DOX) related liver toxicity.PurposeThis study aims to determine the role of hyperoside in DOX related liver toxicity and liver cell damage in vivo and in vitro.MethodsA mouse model of liver toxicity was induced by intraperitoneal injection of DOX, and hyperoside was administered orally for treatment. During this period, the weight and food intake of the mice were recorded. The morphology of mouse liver tissue was observed by hematoxylin and eosin staining. Oxidative stress and inflammatory status in mice were observed through serum inflammatory factors and liver oxidative stress markers. Mitochondrial damage is determined by the degree of mitochondrial DNA damage. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of pyroptosis and genes in the liver and liver cells.ResultsHyperoside can effectively treat DOX-induced oxidative stress and inflammatory status, liver function damage, and hepatocyte necrosis in mice. Further research suggests that the beneficial effect of hyperoside is achieved by inhibiting mitochondrial DNA damage in liver cells.ConclusionThis study indicates that hyperoside improves DOX-induced liver toxicity by inhibiting mitochondrial DNA damage.
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Jiahao Hu,Yuejie Lu,Zhengyang Tan,Jialu Lang,Shihui Wu,Di Chen,Jucong Zhang,Xiaochuan Wu,Qi Zhu,Yuanyan Huang,Jiawen Zhu,Zijian Shen,Xiaolei Hao,Wenzhe Ma,Luwen Zhu,Jiansong Ji,Yongzhong Du
The efficacy of immune checkpoint blockade (ICB) is often constrained by insufficient tumor antigenicity and consequent weak immune activation. Among immunogenic cell death (ICD) modalities, gasdermin-mediated pyroptosis presents a promising strategy to counteract this limitation and potentiate ICB. However, it remains challenging to engineer nanoplatforms that reliably induce pyroptosis via coordinated activation of multiple pathways. Here, we report a sialic acid-functionalized lipid nanoparticle (LNP) that co-delivers GSDME mRNA and a self-assembling small molecule (1541B) as a potent pyroptosis amplifier. Delivered GSDME mRNA bypasses epigenetic silencing and replenishes the pyroptotic substrate, while 1541B self-assembles intracellularly into nanofibers that directly activate caspase-3, cleaving GSDME to initiate non-canonical pyroptosis. Moreover, these nanofibers disrupt mitochondrial function, leading to caspase-1-mediated GSDMD cleavage, thereby amplifying pyroptotic cell death via the canonical pathway. This dual-pathway engagement enhances the release of pro-inflammatory cytokines and remodels the tumor immune microenvironment. As a result, this nano-pyroptosis inducer overcomes resistance to anti-PD-1 therapy, triggering potent systemic anti-tumor immunity and significantly inhibiting tumor growth. Overall, our findings establish a novel therapeutic paradigm for reversing ICB resistance via orchestrated pyroptosis amplification.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）