ACS Applied Materials & Interfaces
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2025
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IF 8.2
Xiaoli Zhang,Wei Zhou,Jin Yu,Ruibin Jiang,Jie Han,Haorong Li,Yang Liu,Xiaohong Fang,Xiaoling Zhang
Immune-suppressive tumor-associated macrophages (TAMs) that infiltrate the tumor microenvironment (TME), along with the presence of the blood–brain barrier (BBB), influence the effectiveness of immunotherapy for glioblastoma. In this study, we report the use of difluoromethylornithine (DFMO), aPD-L1, and Indocyanine Green (ICG) in combination with target TAMs for their repolarization. DFMO repolarizes TAMs by inhibiting the expression of aconitate decarboxylase 1 (ACOD1), while aPD-L1 blocks the PD-1/PD-L1 immune checkpoint on TAMs, achieving efficient phenotypic switching and enhancing the phagocytic activity against glioblastoma (GBM). When combined with the photothermal agent ICG, the photothermal effect induces immunogenic tumor cell death and further strengthens the repolarization of TAMs. This increases the conversion efficiency of TAMs, reverses immune suppression at the tumor site, and transforms the anti-inflammatory “cold” tumor into a pro-inflammatory “hot” tumor. This approach showed better therapeutic effects in an orthotopic glioma model in mice, with the repolarization of our combined treatment DFMO + N-aP@ICG (nanovesicles containing aPD-L1 and ICG), increasing by 179% compared to other combined treatments for glioma. In summary, we propose this innovative immunotherapy for glioma, which effectively penetrates the blood–brain barrier, targets M2-TAMs, enhances the aPD-L1 immune response, and inhibits the proliferation of glioma.
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PubMed
高影响因子
APPLIED ORGANOMETALLIC CHEMISTRY
·
2025
·Vol. 39
·期 7
·e70249
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IF 0
Conghao Liu,Yang Yang,Runzhi Li,Xiaoqing Zhang,Dionisio Zaldivar Silva,Yuefeng Zhao,Ruizhuo Ouyang,Yuqing Miao,Baolin Liu,Shuang Zhou
Three new thiosemicarbazone ligands (L1–L3) were synthesized, followed by their complexation with bismuth (Bi, III) producing the corresponding Bi (III) complexes (I–III). A series of in vitro biological studies of both the ligands and bismuth complexes were well assessed on a panel of human cancer cell lines, A549 and H460, including cytotoxicity assay, inhibition rate, clonogenic assay, scratch assay, and cell apoptotic evaluation. Compared to the ligands, the bismuth complexes displayed greatly enhanced ability to suppress colony formation and cell migration and thus significantly induced apoptosis of human lung cancer cells, sticking out remarkable anticancer activities of the Bi-based complexes. Significantly, Complexes I and III were found to be more active and exhibited potent cytotoxicity against the A549 cancer cell line, with IC 50 values of 2.68 and 1.08 μM, respectively. Accordingly, the antitumor effects of Complexes I and III on lung cancer cell line A549 in vivo human lung model were further investigated to simulate the clinical manifestations of A549 in BALB/c mice. The results indicate that Complex III mostly inhibited A549 xenograft growth in mice, with tumor volume reduced by 94.74% and tumor weight lightened by 98.27%, as compared to control. More importantly, no harmful effect was observed on the mouse liver, spleen, and lung. Good preliminary results obtained in mice reveal the great potential of Bi (III) thiosemicarbazone complexes as anticancer drugs.
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Advanced Science
·
2025
·
IF 14.1
Wei Zhang,Xiangbing Wu,Wenming Li,Haifeng Zhang,Yijun Wang,Jing Xu,Wenhao Li,Yi Qin,Zebin Wu,Gaoran Ge,Shujun Lv,Lu Mao,Liangliang Wang,Dechun Geng
Pro-inflammatory cytokines such as TNF, IL-1, and IL-6 trigger aberrant osteoclastogenesis and result in massive bone loss. During RANKL-induced osteoclastogenesis, pyroptosis of macrophages/preosteoclasts acts as a pivotal mechanism for IL-1β release, thereby promoting osteoclast maturation and bone resorption. In the current study, it is observed that Pinosylvin (PIN), a compound extracted from European red pine, selectively inhibits LPS- and RANKL-induced release of IL-1β effectively reducing osteoclastogenesis. Notably, PIN inhibits the assembly of NLRP3 and the cleavage of GSDMD, pro-IL-1β, and pro-caspase-1, suggesting its therapeutic effects are NLRP3-targeted. Mechanistically, PIN blockes the NEK7/NLRP3 interaction, but not the NLRP3/ASC interaction, through its 3,5-dihydroxy groups by binding to NEK7, thereby inhibiting subsequent pyroptosis and osteoclastogenesis. Importantly, PIN alleviates inflammatory bone loss due to estrogen deficiency, reduces cranial bone destruction from local LPS injections, and improves survival in LPS-induced septic mice. This study uncovers the specific mechanism behind PIN's potent anti-inflammatory effects and identifies a new therapeutic target for NLRP3-driven diseases.
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高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Jieming Zhang,Fangfang Zhou,Xin Du,Meiru Zhang,Suxiao Li,Songtao Niu,Qungang Chang,Yongju He
Cisplatin-based chemotherapy is widely used to combat cancers through an apoptosis pathway. However, drug resistance induced by upregulated glutathione (GSH) in tumor cells and systemic side effects significantly compromise its therapeutic efficacy. The application of nanocarriers with a GSH-scavenging ability is a promising strategy to overcome these obstacles. In addition, ferroptosis has shown great potential in eliminating the limitation of apoptosis-mediated chemotherapeutics. Herein, a multifunctional nanoplatform (S4MON-Cis@TA-Fe3+), loaded with cisplatin in tetrasulfide bonds-bridged mesoporous organosilica nanoparticles (S4MON) and then coated with tannic acid (TA)-Fe3+ metal-phenolic network, is developed for apoptosis–ferroptosis synergistic therapy. In the acidic tumor cells, the outer TA-Fe3+ network is disassembled into Fe3+ and TA, and the internal S4MON-Cis network is exposed. The released TA and endogenous GSH reduce Fe3+ to Fe2+, which significantly increases cellular oxidative stress through the Fenton reaction and GSH consumption. Moreover, S4MON-Cis decreases the intracellular GSH content through redox reaction between tetrasulfide bonds and GSH, which further augments cellular oxidative stress and triggers nanoparticle degradation to release cisplatin. Subsequently, cisplatin induces apoptosis and elevates the cellular hydrogen peroxide level to improve the Fenton reaction efficiency. The multiple oxidative stress amplification greatly promotes lipid peroxidation and glutathione peroxidase 4 downregulation, boosting tumor ferroptosis. Meanwhile, the dual GSH elimination significantly improves the antitumor effect of cisplatin. As a result, S4MON-Cis@TA-Fe3+ exhibits effective tumor growth inhibition through self-enhanced apoptosis–ferroptosis synergistic therapy, which holds great promise for cancer therapy.
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高影响因子
FREE RADICAL RESEARCH
·
2025
·
IF 2.9
Doudou Lu,Ling Yuan,Zhaozhao Wang,Duojie Xu,Fandi Meng,Shumin Jia,Yahong Li,Weiqiang Li,Yi Nan
The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells’ wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
·
IF 9.7
Bowen Song,Ziye Zhao,Zhanhong Qiao,Ji Li,Dawei Chen,Ming Zhao,Haiyang Hu
Despite significant advancements in tumor immunotherapy, challenges including insufficient immunogenicity and immunosuppressive microenvironment continue to hinder therapeutic effect. The immunogenic cell death (ICD) enhances the tumor immune microenvironment and potentiate immunotherapy response. Certain chemotherapeutic agents can induce ICD; however, their limited immunogenicity, poor tumor-site targeting, and low tumor permeability restrict their efficacy. Herein, bacteria-driven liposomes were designed. Liposomes co-loaded with mitoxantrone (MTO) and iron ions (Fe 3+ ) were engineered to leverage the hypoxia-responsive properties of Escherichia coli Nissle 1917 (EcN) for precise tumor-site targeting. In the acidic tumor environment, mitoxantrone/ferric ions liposomes (LFM) released Fe 3+ and MTO. Intracellular Fe 3+ is reduced to Fe 2+ , catalyzing the Fenton reaction to generate reactive oxygen species (ROS) and induce ferroptosis. Concurrently, mitoxantrone (MTO) exerts direct cytotoxic effects on tumor cells. The synergistic interplay of these mechanisms significantly enhances the immunogenicity of tumor cells, triggering ICD and subsequently activating systemic antitumor immune responses. The drug delivery system constructed in this study integrated chemotherapy, ferroptosis, and immune activation, providing an innovative and effective strategy for tumor therapy. This approach paves the way for advanced combination therapies in cancer treatment.
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Small
·
2025
·
IF 12.1
Shiyu Xu,Yin Yuan,Yukun Pan,Huihui Zhang,Siyuan Yin,Xinya Zhang,Yayun Zhang,Sheng Dai,Huawei Shen,Yongsheng Li,Dechao Niu
The unsaturated coordination alters the electronic structure of metal atoms, exposing more active sites, and thereby demonstrating high catalytic activity. It is extremely difficult to precisely regulate the unsaturated coordination environment of single-atom catalysts due to the thermodynamically unstable structure. Herein, a facile “micelle-confined oxidative crosslinking and coupled coordination” strategy is proposed to construct a copper single-atom catalyst with an unsaturated Cu-N 2 coordination structure in a confined silica-carbon framework (Cu SA@MCSN), which demonstrate unique pH-dependent multiple-enzymatic activity (peroxidase (POD)-like activity in an acidic environment with a low K m of 6.9 mM and V max of 6.3 × 10 −8 M s −1 and superoxide dismutase (SOD)- and catalase (CAT)-like activity under neutral conditions). Density functional theory calculations also further confirm that the asymmetric Cu-N 2 sites with edge configurations exhibit a strong adsorption capacity for oxygen-containing intermediates showing a faster reaction rate compared to their saturated coordination structure. More importantly, the metformin (MET)-loaded Cu SA@MCSN demonstrates multi-pathway antibacterial ability in acidic microenvironments and long-term anti-inflammatory effects in neutral microenvironments through the downregulation of pro-inflammatory factors and the up-regulation of anti-inflammatory and tissue regeneration factors on a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds.
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高影响因子
Advanced Science
·
2025
·
IF 14.1
Jianxin Ye,Peng Hu,Rui Zhang,Lei Zhou,Zonghua Luo,Yanan Chen,Shengzhe Ruan,Mengyi Zhu,Huaze Ding,Yike Qian,Yan Xing,Tong Meng,Changping Wang,Dianwen Song
Bone is the most common site of breast cancer metastasis, yet understanding the intricate mechanisms and potential therapeutic targets remains nascent. Here it is reported that breast cancer establishes a hyperglycemic bone pre-metastatic niche before migrating to bone tissue and further enhances glucose metabolism following metastatic colonization. An intervention strategy is subsequently proposed targeting glucose metabolism utilizing a biomimetic-engineered enzyme-based nanoplatform. This platform's membrane shielding reduces the interaction between engineered glucose oxidase and circulating glucose, while the engineered enzyme specifically targets glucose metabolism, enabling self-amplifying starvation combined with selective chemotherapy. Such precision can precisely inhibit breast cancer bone metastases and block distal tumor dissemination. This study provides novel insights into the role of glucose metabolism in the pre-metastatic niche and presents a proof-of-concept for metabolic-targeted strategies in breast cancer bone metastasis treatment. This approach holds significant promise for improving therapeutic outcomes in metastatic breast cancer by targeting the metabolic vulnerabilities of the bone microenvironment and halting systemic tumor spread.
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高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Haisha Lu,Tianle Zhang,Jian Liang,Jinxiang Zeng,Junwei He,Jixiao Zhu,Jinbin Yuan,Xuelan Fu,Huiqing Li,Guoyue Zhong
Gastric ulcer (GU) is one of the most common diseases in humans. Liuwei Muxiang powder (LWMXP), a Tibetan medicine, is a traditional compound prescription used for treating GUs. However, there is currently no in-depth report on its effective substances and action mechanisms. In this study, first, the method of serum pharmacochemistry was adopted to identify 61 prototype components and 18 metabolites of LWMXP. Then, network pharmacology was used to predict the core components, key targets, and important pathways of LWMXP for treating GUs. Subsequently, the effects of LWMXP and its core components on the viability, biochemical indices, cell cycle, reactive oxygen species (ROS), and apoptosis rate of gastric epithelial cell line-1 (GES1) cells in the ethanol-induced GU model were explored. After that, molecular docking was utilized to predict the interactions between the positive drug (omeprazole), six core components, and eight key targets of the PI3K-AKT signaling pathway, and Western blot experiment was carried out for verification. Finally, it was determined that LWMXP for treating GES1 cells in the ethanol-induced GU model mainly acts on the PI3K-AKT signaling pathway, and its effective substances include protopine, piperine, eugenol, methyl gallate, gallic acid, and costunolide. This provides ideas for the follow-up research of LWMXP. Graphical First, the main blood-entering components of LWMXP were identified by serum pharmacochemistry methods. Then, the core components, key targets, and important pathways of LWMXP in treating gastric ulcers were screened through network pharmacology. Subsequently, the effects of LWMXP and its core components on the activity, biochemical indicators, cell cycle, ROS, and apoptosis rate of GES1 cells in the ethanol-induced gastric ulcer model were explored. Then, molecular docking was used to validate the interactions between the positive control drug (omeprazole), six core components, and eight key targets in the PI3K-AKT signaling pathway. Finally, Western blot experiments were carried out to verify the effects of LWMXP and the six core components on the aforementioned targets, ultimately identifying the bioactive substances and mechanisms of LWMXP in the treatment of gastric ulcer.
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高影响因子
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2025
·
IF 1.9
Xiao-Liang Zhao,Kai-Li Qi,Hui Han,Hai-Dong Wen,Yan-Mei Liu,Qing-Song Zhou,Yuan-Yuan Ma,Cun-Jin Wang,Jing Zhang,Ji Zhang,Wei-Jie Zhang
Olive pomace, a by-product of olive oil production, remains underexplored despite its potential environmental and economic benefits. This study sequentially extracted three polysaccharides (OERC, OERH, and OERA) from olive pomace using water at room temperature, hot water (80 °C), and 2% Na2CO3 solution (60 °C). Characterization through UV–Vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, high-performance liquid chromatography, and Congo red experiment revealed that these polysaccharides are heteropolysaccharides primarily composed of glucose, mannose, rhamnose, and galactose, each with distinct molar ratios. The polysaccharides exhibited significant antioxidant activity by scavenging hydroxyl, DPPH, and superoxide radicals, with OERC showing the highest potency. They also repaired H2O2-induced oxidative damage in HepG2 cells, with OERC at 400 μg/mL and OERH/OERA at 200 μg/mL displaying optimal efficacy. Additionally, these polysaccharides effectively inhibited α-glucosidase activity, enhanced glucose consumption, and increased glycogen content in insulin-resistant models, thereby exerting hypoglycemic effects. Furthermore, they promoted proliferation, phagocytosis, and nitric oxide release in RAW264.7 macrophages, demonstrating immunomodulatory effects. These results indicate that sequential extraction under varying conditions is an effective method for preparing polysaccharides. The three polysaccharides isolated in this study show great potential for development as functional products with antioxidant, hypoglycemic, and immunomodulatory applications.
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高影响因子
PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Wei Zhao,Di Zou,ZhengYang Wang,GuiQiang Wang,HongBo Jiang,Guy Smagghe,JinJun Wang,DanDan Wei
BACKGROUND Bactrocera dorsalis (Diptera: Tephritidae) is a highly adaptable invasive pest that causes significant economic losses. Long-term chemical control strategies have led to high levels of insecticide resistance and severe environmental risks. C-type lectins (CTLs), key pattern recognition receptors in insect innate immunity, are named for their calcium-dependent carbohydrate recognition domains (CRDs) and they play a critical role in detecting and binding to foreign pathogens. This study aims to identify B. dorsalis CTLs (BdCTLs) and investigate their roles in pathogen defense. RESULTS A total of 42 BdCTL genes were identified. Based on the number of CRDs, 36 genes were classified into the S subfamily, while the remaining six were assigned to the X subfamily. Spatio-temporal expression analysis by qPCR revealed that BdCTL genes were expressed throughout all developmental stages with a higher expression observed in the midgut, Malpighian tubules, and fat body. The expression levels of BdCTL-S4 , BdCTL-S12 , and BdCTL-S31 were significantly upregulated under the infection of the entomopathogenic fungus Beauveria bassiana . Notably, BdCTL-S12 also exhibited upregulated expression patterns in response to four different pathogens bacteria with sustained expression over time. Using RNA interference (RNAi), we successfully knocked down BdCTL-S12 expression, achieving a silencing efficiency of 68%. Survival assays demonstrated a 10–30% reduction in the survival rate of B. dorsalis after pathogen infection following dsRNA injection compared to the control group. Further in vitro experiments confirmed that BdCTL-S12 can agglutinate and bind to pathogens in a calcium-dependent manner. This binding was competitively inhibited by polysaccharides, underscoring a key functional mechanism of BdCTL-S12 in pathogen recognition. CONCLUSION In summary, we identified 42 BdCTLs and demonstrated that BdCTL-S12 is critical for pathogen recognition and immune defense in B. dorsalis . These results advance our understanding of the molecular mechanisms underlying B. dorsalis immunity. Specifically, elucidating the role of CTLs may facilitate the development of microbial-based biological control strategies (e.g., entomopathogenic fungi or bacteria) against this invasive pest. Additionally, RNAi-mediated knockdown of CTL-encoding genes could weaken the immune system of Bactrocera flies, increasing their susceptibility to microbial infections and thereby enhancing the effectiveness of biological control. © 2025 Society of Chemical Industry.
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Jinsong Che,Yi Zhang,Shida Li,Xiujuan Li
The antioxidant and anti-inflammatory properties of Xianju wheat paste (XJWP), a traditional condiment originating from Hubei Province, China, were evaluated for the first time. XJWP is an essential appetizer and condiment for local residents. It is also utilized for its anti-inflammatory properties in treating minor wounds in daily life, which suggests that it possesses bioactive properties, notably anti-inflammatory effects. In this study, five extracts of XJWP were obtained using different polar solvents, and all of them exhibited antioxidant activity through DPPH, •OH, ABTS free radical scavenging tests and ferric reducing antioxidant power. Subsequently, a lipopolysaccharide-induced RAW264.7 cell model was established to evaluate their anti-inflammatory effects. All of the XJWP extracts significantly inhibited NO secretion in the cells ( p < 0.05), and ethyl acetate extract (XJ-EA) exhibited the most potent effect characterized by an EC 50 value of 61.92 μg/mL. At a concentration of 40 μg/mL, XJ-EA suppressed the overproduction of TNF-α, IL-6, and IL-1β to normal levels. The in vivo anti-inflammatory activity of XJ-EA was evaluated using a mouse model of ear edema induced by xylene exposure. The result revealed that high-dose XJ-EA reduced the ear edema rate in mice by 56 %, mitigated oxidative damage, inhibited the activity of COX-2 and iNOS, decreased the levels of prostaglandin E2 and NO, and achieved significant anti-inflammatory effects ( p < 0.05). Qualitative analysis identified 21 potential anti-inflammatory components in XJ-EA, and molecular docking studies showed favorable interactions with iNOS and COX-2. These findings provide a theoretical foundation for the development of XJWP as a functional condiment, and even as a natural antioxidant and anti-inflammatory drug resource to improve public health and increase the economic value of this product.
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高影响因子
危险品化学品经营许可证（带存储）