MOLECULES
·
2025
·Vol. 30
·期 8
·1667
·
IF 4.6
Zenan Chen,Wei Li,Yan Zhao,Dingrui Liu,Jiahong Han,Enbo Cai
Tumorigenesis and progression are closely associated with apoptosis and primarily regulated by mitochondria, which are considered major targets for cancer therapy. In this study, twelve novel icaritin (ICT) derivatives were designed and synthesized, four of which were specifically targeted to mitochondria. Biological studies demonstrated that all compounds containing triphenylphosphine (TPP+) exhibited a substantial increase in antitumor activity compared to ICT and control compounds while also exhibiting notable selectivity for tumor cells over normal cells. Among these derivatives, Mito-ICT-4 exhibited the strongest antiproliferative effect, with an IC50value of 0.73 ± 0.06 μM for BEL-7402 cells, which is 29 times lower than that of ICT, and an IC50value of 67.11 ± 2.09 μM for HEK293 cells, indicating approximately 33-fold selectivity for tumor cells. High-performance liquid chromatography (HPLC) analysis revealed that Mito-ICT-4 significantly accumulated in the mitochondria of BEL-7402 cells, with the level of accumulation approximately 2.5 times greater than that of ICT. Further investigations demonstrated that upon entering the mitochondria of tumor cells, Mito-ICT-4 downregulated SIRT3 protein expression, disrupted intracellular redox homeostasis, and led to a substantial increase in mitochondrial ROS levels, abnormal CypD-dependent MPTP opening, mitochondrial membrane potential depolarization, and ROS release into the cytoplasm, ultimately triggering ROS-mediated apoptosis in BEL-7402 cells. Transcriptomic analysis identified differentially expressed genes and enriched pathways, highlighting the ROS-mediated p38-MAPK signaling pathway as a key mediator of Mito-ICT-4-induced mitochondria-dependent apoptosis. The effects of Mito-ICT-4 on the expression of key genes (SIRT3, CypD, P-MKK6, P-P38, and DDIT3) were further validated by qRT-PCR and Western blot analysis, with results aligning with transcriptomic data. The novel ICT derivatives synthesized in this study, with mitochondria-targeting functionality, provide a basis for the development of targeted antitumor drugs.
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Magnetochemistry
·
2026
·Vol. 12
·期 7
·74
·
IF 2.8
Bin Chen,Ge Gao,Yuhua Liu,Wei Ding,Hong Li
Conventional water treatment relies on sequential flocculation and disinfection, which inflates infrastructure costs and heightens the risk of disinfection byproduct formation. Here, we report a magnetic lignin-based flocculant (LS-DMC-AM@Fe3O4) that integrates flocculation, sterilization, and rapid magnetic separation within a single material. The composite was synthesized by thermally initiated graft copolymerization of methacryloyloxyethyl trimethylammonium chloride (DMC) and acrylamide (AM) onto sodium lignosulfonate (LS), followed by incorporation of Fe3O4nanoparticles (NPs) at 15 wt% loading; the product exhibited a saturation magnetization of 12.8 emu g−1. LS-DMC-AM@Fe3O4achieved 98.2% kaolin turbidity removal at 1 mg L−1and 98.6%E. coliremoval at 8 mg L−1, and displayed a markedly broader effective dosage window than its non-magnetic analog. We attribute this broadened window to Fe3O4-enhanced membrane disruption, which liberates anionic intracellular contents that buffer excess cationic charge and thereby suppress restabilization. The bactericidal efficiency reached 90% at 18 mg L−1, 1.6-fold higher than LS-DMC-AM, governed by a synergistic dual mechanism: quaternary ammonium contact-killing coupled with Fe3O4NP-induced intracellular reactive oxygen species (ROS) accumulation. Under an external magnetic field, flocs underwent rapid phase separation and displayed enhanced shear-regrowth capacity (E. colifloc recovery factor: 53% vs. 26%); Fe3O4NPs were recovered at >95% efficiency over two cycles. Despite higher unit production costs, LS-DMC-AM@Fe3O4delivers competitive per-unit-volume treatment economics through its ultralow effective dosage and magnetic seed recyclability. These results establish a viable strategy for engineering multifunctional, recyclable flocculants from industrial lignin waste.
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Antioxidants
·
2026
·Vol. 15
·期 5
·649
·
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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CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2026
·
IF 3.5
Qingmao Yang,Anyan He,Junyan Tan,Weichen Zhao,Haoyi Wu,Shengning Luan,Wei Feng,Chun Shen
Developing a novel EPCS combining GOase with Au/TiO 2 . • Achieving ∼92.3% DFF yield with ∼97.0% selectivity within 2 h in pure water. • The by-product H 2 O 2 is in-situ decomposed into O 2 by Au/TiO 2 . • •OH, •O 2 – and O 2 precisely required for GOase activation generated by Au/TiO 2 . 2,5-Diformylfuran (DFF), as the oxidation product of the biomass platform molecule 5-hydroxymethylfurfural (HMF), has attracted considerable attention because of its broad utility as a precursor for pharmaceuticals, renewable polymers, and other functional products. Efficient oxidation of HMF into DFF through biocatalysis in pure water is extremely desirable but still faces significant challenges: complex multi-enzyme systems and low reaction efficiency. Herein, we develop a novel enzyme-photo-coupled catalytic system (EPCS) combining GOase with Au/TiO 2 photocatalyst, achieving “waste-to-wealth”. The mechanism study reveals that the Au/TiO 2 acts as the role of “killing two birds with one stone”: in-situ decomposing inhibitory H 2 O 2 by-product into O 2 and H 2 O, thereby mitigating enzyme inhibition; and ingeniously generating reactive oxygen species (ROS) (hydroxyl radicals (·OH) and superoxide radicals ( )) and regenerative O 2 that precisely are required for GOase activation. Under visible light conditions, the EPCS achieves (92.3±1.4)% DFF yield with (97.0±0.8)% selectivity within 2 h, significantly outperforming the single enzyme system (DFF yield: (40.9±2.4)%). The “green chemistry” concept is implemented in the EPCS, which provides a generalizable strategy for developing efficient, green, and concise oxidation systems by turning a toxic by-product into catalytic promoters. Download: Download high-res image (335KB) Download: Download full-size image
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Pharmaceutics
·
2026
·Vol. 18
·期 5
·602
·
IF 6.9
Jiangtao He,Chunyu Gan,Tongxia Chi,Jia Liu,Tuya Bai,Xin Wu,Guodong Liang,Ruijuan Li,Yuheng Ma
Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD.
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DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2025
·
IF 2.2
Yanli Zhao,Yimu Li,Yan Chen,Yuanyuan Li,Lingbing Li,Wei Xu
Objective The aim of this study was to develop a chemotherapy drug paclitaxel (PTX) and a tumor specific ROS generation agent β-lapachone(LAP) co-loaded human serum albumin (HSA) based nanoparticles (ANPs) for synergistic anticancer therapy.Significance: Albumin based nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. In this study, we mimicked the natural fatty-acid binding process in vivo to construct ANPs to synergistically elevate ROS with β-lapachone for cooperative cancer therapy.Methods: Firstly a polyethylene glycol monostearate(PGM) modified redox-sensitive paclitaxel prodrug(PTX-SS-PGM) was synthesized and stearic acid capable of binding with HSA was introduced. Furtherly, a LAP/PTX-SS-PGM complex was engineered through the π − π stacking interaction and H-bonding between LAP and PTX. The PTX and LAP co-loaded ANPs (PTX-SS-PGM&LAP@HSA) were obtained through the binding between LAP/PTX-SS-PGM complex and HSA.Results: The percentage of apoptosis for PTX, Abraxane®, PTX-SS-PGM@HSA ANPs and PTX-SS-PGM&LAP@HSA ANPs was 8.17%, 9.53%, 15.17% and 28.6%, respectively, demonstrating synergistic cytotoxicity effect. The in vivo imaging test confirmed that PTX-SS-PGM&LAP@HSA had targeting ability to tumor tissues. The obtained ANPs exhibited better tumor growth inhibition in vitro and in vivo.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jingjing Wang,Pingping Qu,Fuhan Wang,Man Qian,Ziyi Li,Mengyao Guo,Xuejiao Gao
Zearalenone is an estrogen-like mycotoxin produced by Fusarium fungi. Growing evidence shows that ZEA causes multisystem damage via oxidative stress. Glycyrrhizic acid (GA), from Glycyrrhiza glabra, has anti-inflammatory/antioxidant properties. The mechanisms of GA and ZEA in chicken pulmonary oxidative stress and inflammation remain elusive. Therefore, we established zearalenone-exposed chicken lung and CP-II cells models. ZEA exposure triggers an inflammatory cascade via the ROS-NF-κB axis, activating NLRP3 inflammasomes and promoting the release of proinflammatory factors. It also increased the apoptosis-related factors and fibrosis-related factors. GA treatment reduced oxidative stress, inflammation, and apoptosis, while suppressing fibrosis. This study reveals that GA reverses lung tissue injury by suppressing oxidative stress, inflammation, and the apoptosis-necrosis network through regulating the NF-κB/NLRP3 signaling axis by scavenging ZEA-induced reactive oxygen species (ROS). These results elucidate the antioxidant mechanism of GA and provide insights into the toxicology of ZEA.
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Journal of Macromolecular Science Part B-Physics
·
2024
·
IF 1.2
Chunbo Pan,Guanghua Gu
Potentially beneficial novel approaches to cancer treatment, particularly for drug-resistant malignancies, include synergistic therapies that combine chemotherapy with photothermal therapy. In our research described here we developed a unique silk protein-functionalized gold nanoparticles (AuNP) formulation for effective combinatorial photothermal therapy (PTT) and chemotherapy against ovarian cancer cells. The main goal of the present investigation was the fabrication of silk protein-functionalized gold nanoparticles (AuNPs) embedded with Dichlororuthenium (II) (p-cymene) (1,3,5-triaza-7-phosphaadamantane) (RAPTA-C) molecules (RC@Au-SF NPs) to improve apoptosis in ovarian cancer cells. The structural and morphological analyses of the prepared nanoformulations confirmed the successful fabrication and uniform distributions of Au-SF NPs with RAPTA-C. We observed the RC@Au-SF NPs showed enhanced toxicity to ovarian cancer cell lines with near infrared (NIR)-light exposure. The RAPTA-C loaded Au-SF NPs significantly improved the internalization of the nanoparticles inside the cells resulting in intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) and cell apoptosis on ovarian cancer (SKOV-3 & A2780) cells. We suggest the outcome of the developed formulation for anti-ovarian cancer action will be highly promising for future cancer control research.
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POULTRY SCIENCE
·
2025
·Vol. 104
·期 4
·104918
·
IF 4.2
Linghuan Luo,Ming Ge,Yiming Sun,Yihan Hu,Xiaoyi Yang,Ruili Zhang
2-Ethylhexyl diphenyl phosphate ( EHDPHP ) is a pervasive environmental pollutant known to induce oxidative damage in organisms; however, its precise mechanisms of toxicity remain unclear. Furthermore, limited research has been conducted on potential therapeutic agents to counteract EHDPHP toxicity. Glycyrrhizic acid ( GA ), a triterpenoid saponin compound with recognized antioxidant, anti-inflammatory, and immunomodulatory properties, represents a promising candidate for mitigating EHDPHP-induced oxidative injury. In chickens, the thymus is the main immune organ. This study aims to investigate the mechanism of EHDPHP-induced thymus damage and the role and mechanism of GA intervention in this process. A potential ‘EHDPHP/GA-Target-Oxidative Stress ( OS )’ network was constructed using network biology. A model of EHDPHP-induced chicken thymic injury was established by continuous oral administration of EHDPHP (160 mg/kg) for 42 days. Moreover, the mechanism of action by which GA antagonizes EHDPHP-induced oxidative damage was explored using MDCC-MSB1 cells in vitro. Network biology analyses showed that ‘EHDPHP/GA-OS’ targets were mainly enriched in the adipocytokine and apoptotic signaling pathways. Molecular docking demonstrated the binding interactions of GA and EHDPHP with Kelch-like ECH-associated protein 1 ( Keap1 ), nuclear factor erythroid 2-related factor 2 ( Nrf2 ), and signal transducer and activator of transcription 3 ( STAT3 ) proteins. Both in vitro and in vivo experiments revealed that GA attenuated EHDPHP-induced damage to thymus and MDCC-MSB1 cells, as evidenced by reductions in oxidative stress markers (ROS, MDA, T-AOC, SOD, and GSH-Px), inflammation factors (NF-κB, IL-6, and TNF-α), and the apoptotic factor (Caspase 3) expression. GA treatment increased the expression of Nrf2 and HO-1 while reducing the expression of Keap1, JAK1, Phospho-JAK1 ( P-JAK1 ), STAT3, and Phospho-STAT3 ( P-STAT3 ). Furthermore, the protective effect of GA against EHDPHP-induced MDCC-MSB1 cell injury, as well as its inhibition of the JAK1/STAT3 pathway, was diminished by the Nrf2 inhibitor ML385. These findings suggest that GA exerts its protective effects through Nrf2 and mitigates EHDPHP-induced thymic injury in chickens by modulating the crosstalk between the Nrf2/ROS/STAT3 signaling pathways. Overall, this study highlights the novel role of GA in treating EHDPHP-induced injury and underscores its potential application in diseases treatable with Nrf2 activators.
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Xiyue Xue,Yanpeng Chen,Yuxin Xiao,Saidi Wang,Hongjie Zhang,Jin Wang,Wen-Hui Zhang
This study pioneers a sustainable “waste-to-wealth” strategy for fabricating a high-performance, pH-universal Fenton-like catalyst (FeCu 2 @BC T4 ) through the one-step co-pyrolysis of acid-precipitated black liquor (APBL) and Fenton sludge with a copper precursor. The innovation lies in the precise engineering of a Fe 0 /Fe 3 O 4 heterojunction synergistically coupled with Cu 0 nanoparticles on a functional APBL-derived biochar. By tuning the Cu/Fe mass ratio and pyrolysis time, the phase composition and electron-transfer properties were optimized. The resulting catalyst exhibits exceptional activity and stability across a broad pH range (3–9), achieving >92.3% methylene blue degradation within 60 min, and demonstrates superior removal efficiency toward various cationic dyes (rhodamine B, crystal violet, malachite green) and an anionic dye (methyl orange). Mechanistic investigations reveal a clear pH-governed transition of reactive oxygen species (ROS) pathways: under acidic conditions (pH 3), •OH-dominated homogeneous–heterogeneous catalysis prevails; under neutral conditions, the system shifts to a heterogeneous process driven by synergistic •OH/ 1 O 2 oxidation. This unique ROS switch is sustained by efficient electron mediation from the biochar matrix, coupled with robust electron supply and transfer enabled by the Fe 0 /Fe 3 O 4 heterojunction and Fe Cu galvanic coupling. This work provides a novel paradigm for converting industrial solid wastes into advanced catalytic materials with a well-elucidated mechanism, effectively overcoming the critical pH limitation of conventional Fenton technologies and showing broad application prospects for organic wastewater remediation.
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CHEMICAL RESEARCH IN TOXICOLOGY
·
2016
·
IF 3.025
Zixuan Liu,Qiong Shi,Xiufang Song,Yuxin Wang,Yawen Wang,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ) is a downstream metabolite of pentachlorophenol (PCP). Previously, we demonstrated that TCBQ caused cytotoxicity due to mitochondrial-related apoptosis. Here, we confirmed the upregulation of death receptor 5 (DR5) followed by the construction of the death-inducing signaling complex (DISC). We also detected the activation of the caspase cascade, which was correlated with TCBQ-induced apoptotic cell death in PC12 cells. The upregulation of DR5 included transcriptional activation and de novo protein synthesis in response to TCBQ. We also identified the endoplasmic reticulum (ER) as a new target for the TCBQ challenge in PC12 cells. The protein kinase R-like ER kinase/eukaryotic translation initiation factor 2α (PERK/eIF2α)-mediated activating transcription factor 4 (ATF4)-ATF3-C/EBP homologous protein (CHOP) signaling pathway contributed to the process of TCBQ-induced ER stress. Blocking ATF4, ATF3, or CHOP signaling by gene silencing technology resulted in decreased cell apoptosis after exposure to TCBQ. Finally, NAC ameliorated TCBQ-induced apoptosis and ER stress, which illustrated that TCBQ-induced apoptosis is somehow ROS-dependent. In summary, this study provided important mechanistic insight into how TCBQ utilizes ER stress-related signaling to exhibit pro-apoptotic activity in PC12 cells.
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