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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 5 ·2493 · IF 4.9

Iron Stress Affects the Growth and Differentiation of Toxoplasma gondii

Zhu Ying,Meng Yin,Zifu Zhu,Zheng Shang,Yanqun Pei,Jing Liu,Qun Liu

Iron is an indispensable nutrient for the survival ofToxoplasma gondii; however, excessive amounts can lead to toxicity. The parasite must overcome the host’s “nutritional immunity” barrier and compete with the host for iron. SinceT. gondiican infect most nucleated cells, it encounters increased iron stress during parasitism. This study assessed the impact of iron stress, encompassing both iron depletion and iron accumulation, on the growth ofT. gondii. Iron accumulation disrupted the redox balance ofT. gondiiwhile enhancing the parasite’s ability to adhere in high-iron environments. Conversely, iron depletion promoted the differentiation of tachyzoites into bradyzoites. Proteomic analysis further revealed proteins affected by iron depletion and identified the involvement of phosphotyrosyl phosphatase activator proteins in bradyzoite formation.Keywords:Toxoplasma gondii;iron depletion;iron accumulation;bradyzoite differentiation

CAS / MDL: 7783-85-9
研究领域: 寄生虫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2020 · IF 7.489

Interfacial and emulsion characterisation of chemically modified polysaccharides through a multiscale approach

Yue Wei,Yanping Xie,Zhixiang Cai,Yalong Guo,Min Wu,Pengguang Wang,Ruiqi Li,Hongbin Zhang

Hypothesis The structural modification of natural emulsifiers may greatly impact their interfacial behaviours and bulk properties. The relationship between the microscopic interfacial viscoelasticity and the macroscopic emulsion stability in emulsifiers with different degrees of modification can be clarified using a multiscale approach. Experiments A polysaccharide emulsifier of corn fibre gum (CFG) with different octenyl succinate anhydride (OSA) contents was used to obtain a broad variety of interfacial properties . Interfacial adsorption kinetics and viscoelastic responses were measured by combining interfacial shear rheology and quartz crystal microbalance with dissipation monitoring, and the emulsion properties (droplet size and physical stability) at other scales were evaluated. Findings Compared with native CFG, esterified CFG formed thick interfacial films with higher elasticity and viscosity , and their corresponding emulsions showed greater stability. There exists a satisfactory correlation between interfacial rheological properties and emulsion stability. However, such a satisfactory correlation can not be established among the degree of esterification of CFG, interfacial viscoelasticity and stability since depletion flocculation might occur in the emulsion stabilized by the OSA-CFG with the highest OSA content, which induced inferior bulk stability but exerted no impact on the measured interfacial properties. We propose that the depletion flocculation is responsible for this imperfection and provide detailed explanations.

研究领域: 食品科学 · 胶体化学 · 表面化学
✓ 已验证 DOI 高影响因子
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MOLECULES · 2024 ·Vol. 29 ·期 8 ·1845 · IF 4.2

Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy

Sitong Lai,Bing Wang,Kunhui Sun,Fan Li,Qian Liu,Xie-An Yu,Lihe Jiang,Lisheng Wang

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

研究领域: 药学 · 肿瘤学 · 纳米医学
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Gold nanoclusters-decorated graphitic carbon nitride nanocomposites with antibacterial and anti-biofilm activities

Yufeng Luo,Hean Zhang,Qianling Cui,Hui Li,Lidong Li

Gold nanoclusters (AuNCs) are of great potential in antibacterial field, but their unsatisfactory stability as a result of high surface free energy limits their practical applications. One efficient solution is loading the ultrasmall AuNCs onto a substrate or matrix. In this work, graphitic carbon nitride (CN) nanoparticles were firstly functionalized with imidazole groups via a photocatalytic reaction. Then, AuNCs were in-situ synthesized on surface of CN by using imidazole moieties as the reducing and stabilizing ligands via formation of Au-N bonds. Transmission electron microscopy (TEM) analysis of the obtained CN-AuNC nanocomposites verified the uniform distribution of AuNCs with a mean size of 1.8 nm on CN surface. Since the coordination strength of Au-N bond is weaker than that of Au-S bond, ligand exchange can occur for the imidazole-protected AuNCs due to ligand exchange in the presence of thiol compounds. Accordingly, the obtained CN-AuNC nanocomposites exhibited thiol depletion ability. The AuNCs slowly released from the CN surface can enter Escherichia coli ( E. coli ) due to their ultrasmall size, consume bio-thiols reducing species and increase the oxidative stress , which effectively killed the bacteria and inhibited subsequent biofilm formation . This paper provides a promising bactericidal nanocomposite with intrinsic properties for sterilization.

研究领域: 材料科学 · 微生物学 · 纳米医学
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RSC Advances · 2024 ·Vol. 14 ·期 21 ·15106-15111 · IF 3.9

Mechanism insight into the high-efficiency catalytic killing of E. coli by metal–phenolic network as a nanozyme

Weiyun Guo,Chaoyun Wu,Guanghui Li,Yonghui Wang,Shenghua He,Jihong Huang,Xueli Gao,Xiaoyue Yue

Glutathione (GSH) as an antioxidant greatly attenuates the reactive oxygen species (ROS) treatment strategy based on peroxidase-activity nanozymes. Therefore, nanozymes with multiple properties that generate ROS and further GSH-depletion functions would be of great benefit to improve antimicrobial efficacy. Herein, focusing on the green, safe and abundant functional prospects of metal–phenolic networks (MPNs) and the strong prospect of biomedical applications, we have synthesized copper tannic acid (CuTA) nanozymes with dual functional properties similar to peroxidase-like activity and GSH depletion. CuTA can catalyze the decomposition of H2O2 to hydroxyl radicals (˙OH). In addition, CuTA nanozymes can efficiently deplete available GSH, thus enhancing ROS-mediated antimicrobial therapy. The antibacterial results show that CuTA has an excellent antibacterial effect against E. coli.

研究领域: 生物医学 · 材料科学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Chemistry Frontiers · 2021 ·Vol. 5 ·期 5 ·2442-2451 · IF 6.482

Benzoperylene-grafted and Cu2+ chelated polymeric nanoparticles for GSH depletion and chemodynamic therapy

Niu Niu,Huipeng Zhou,Na Yang,Dong Wang,Cong Yu

Polymeric nanoparticles that can respond to a specific tumor microenvironment (TME) show great potential as anticancer agents. In this study, a highly water-soluble polymeric nanoparticle BPP was obtained via atom transfer radical polymerization (ATRP). The strong tendency of self-aggregation of the grafted aromatic benzoperylene facilitated the self-assembly of the polymer into nanoparticles. BPP showed strong excimer emission and could chelate with various metal ions with quenched emission. Cu2+ was then chelated with BPP to form BPC nanoparticles, which were subsequently used as chemodynamic therapy agents. After entering into the cancer cells, BPC could deplete GSH and produce Cu+. Cu+ reacted with intracellular H2O2 and generated toxic hydroxyl radicals (˙OH) via the Fenton-like reaction, which had a fast reaction rate in TME. Because of the high GSH and H2O2 concentrations in tumor cells, BPC NPs exhibited selective cytotoxicity to cancer cells. Additionally, the excimer fluorescence of BPC recovered after entering into the cancer cells, denoting the potential for real time tracking/visualization of drug delivery. The in vivo results also demonstrate that BPC NPs efficiently inhibited tumor growth without obvious systemic toxicity. As a novel Cu2+ chelated polymeric nanomaterial responsive to TME, BPC NPs show excellent potential in chemodynamic cancer therapy.

研究领域: 生物医学工程 · 癌症治疗 · 材料科学
✓ 已验证 DOI 高影响因子
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Cell Reports Methods · 2022 · IF 0

Bacteriophages allow selective depletion of gut bacteria to produce a targeted-bacterium-depleted mouse model

Yanqing Li,Feng Zhu,Yan Li,Shunli Pan,Hongliang Wang,Zai Yang,Zhihao Wang,Zhenyu Hu,Jianfeng Yu,Joseph D Barritt,Tianhui Li,Xi Liu,Yawen Wang,Xiancang Ma,Bing Liu

The gut microbiome is essential for human health. Mouse microbiota models, including gnotobiotic mice, are the most prominent tools to elucidate the functions of gut bacteria. Here, we propose a targeted-bacterium-depleted (TBD) model using lytic bacteriophage to selectively deplete gut bacterium of healthy or otherwise defined mice. These phage-treated animals should have a near-complete spectrum of gut bacteria except for the depleted bacterium. To prove the concept, we employed Escherichia coli -specific phage T7 to repress E. coli in the healthy mice. Our results showed that the E. coli- depleted mice exhibited bravery-like behaviors, correlated to the presence of E. coli rather than the equilibrium among gut bacteria. Thus, we demonstrate that the TBD model is a powerful tool to elucidate the function of a specific bacterial species within a near-intact gut microbiota environment and complements gnotobiotic mice models.

研究领域: 微生物学 · 医学研究 · 分子生物学
✓ 已验证 DOI PubMed
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NATURE CELL BIOLOGY · 2025 ·Vol. 27 ·期 8 ·1357-1366 · IF 19.1

Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity

Du Xian,Li Wenyan,Li Guiying,Guo Chenyue,Tang Xuyi,Bao Rujuan,Li Runchang,Huang Haiyan,Xu Shuiyu,Yu Xiaoyan,Han Qiaoqiao,Wan Jie,Li Song,Sun Jiayuan,Zhao Ren,Ye Youqiong,Gao Qiang,Ni Zhi-Yu,Cui Xingang,Zou Qiang

Dietary nutrients are inextricably linked to antitumour immune responses. However, the effect of diet-derived galactose on antitumour immunity remains unclear. Here we show that dietary galactose augments CD8 + T cell immunity to suppress tumour progression. High-galactose feeding drives hepatocyte-derived insulin-like growth factor binding protein 1 (IGFBP-1) production, thus restraining IGF-1 signalling-dependent T cell exhaustion. IGF-1 receptor (IGF-1R) deficiency in T cells potentiates antitumour CD8 + T cell responses and phenocopies high-galactose feeding by preventing T cell exhaustion. Circulating galactose reprograms hepatocyte metabolism to inactivate mTORC1, thereby inducing the production of IGFBP-1 to boost CD8 + T cell function. Furthermore, patients with cancer who have high plasma IGFBP-1 levels exhibit blocked T cell exhaustion and enhanced T cell responses in tumour tissues. These findings reveal that dietary galactose specifically elicits potent antitumour CD8 + T cell responses by facilitating hepatocyte-derived IGFBP-1 production, providing insights into the development of more effective immunotherapies against cancers.

CAS / MDL: 8001-30-7
研究领域: 免疫学 · 肿瘤学 · 分子生物学 · 转化医学 · 代谢调控
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR PHARMACEUTICS · 2023 · IF 4.9

H2O2 Self-Supplying and GSH-Depleting Nanocatalyst for Copper Metabolism-Based Synergistic Chemodynamic Therapy and Chemotherapy

Zhaomin Tang,Shuting Jiang,Wanlan Tang,Qian He,Huangzhao Wei,Chengyu Jin,Shuai Wang,Hui Zhang

Chemodynamic therapy (CDT) that involves the use of Fenton catalysts to convert endogenous hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) constitutes a promising strategy for cancer therapy; however, insufficient endogenous H2O2 and glutathione (GSH) overexpression render its efficiency unsatisfactory. Herein, we present an intelligent nanocatalyst that comprises copper peroxide nanodots and DOX-loaded mesoporous silica nanoparticles (MSNs) (DOX@MSN@CuO2) and can self-supply exogenous H2O2 and respond to specific tumor microenvironments (TME). Following endocytosis into tumor cells, DOX@MSN@CuO2 initially decomposes into Cu2+ and exogenous H2O2 in the weakly acidic TME. Subsequently, Cu2+ reacts with high GSH concentrations, thereby inducing GSH depletion and reducing Cu2+ to Cu+ Next, the generated Cu+ undergoes Fenton-like reactions with exogenous H2O2 to accelerate toxic ·OH production, which exhibits a rapid reaction rate and is responsible for tumor cell apoptosis, thereby enhancing CDT. Furthermore, the successful delivery of DOX from the MSNs achieves chemotherapy and CDT integration. Thus, this excellent strategy can resolve the problem of insufficient CDT efficacy due to limited H2O2 and GSH overexpression. Integrating H2O2 self-supply and GSH deletion enhances CDT, and DOX-induced chemotherapy endows DOX@MSN@CuO2 with effective tumor growth-inhibiting properties alongside minimal side effects in vivo.

研究领域: 肿瘤学 · 生物医学工程 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2024 · IF 15.8

Targeted Liposomes Sensitize Plastic Melanoma to Ferroptosis via Senescence Induction and Coenzyme Depletion

Lanlan Fan,Panyu Du,Yaru Li,Xuefei Chen,Fang Liu,Yuning Liu,Alexey M. Petrov,Xin Li,Zheng Wang,Yanjun Zhao

Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.

CAS / MDL: 8002-43-5 571190-30-2
研究领域: 癌症治疗 · 药学 · 纳米技术 · 肿瘤学 · 细胞生物学 · 分子生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Construction of an anti-anionic-depletion layer to mitigate the tip deposition effect for dendrite-free zinc anode

Xiaohui Li,Dan Qiu,Qiancheng Zhou,Ze Yang,Xing Zhou,Wenping Wang,Chenchen Wei,Ting Zou,Ying Yu

Rechargeable aqueous zinc-ion batteries have been plagued by the well-known problem of zinc dendrite formation. This issue mainly arises from the inherent depletion of anions in the vicinity of the zinc anode during deposition process, leading to a strong spatial electric field that influences Zn 2+ cations deposition and triggers dendrite growth. Herein, the anti-anionic-depletion strategy is proposed that involves anions anchored in the surface region of zinc anode to mitigate the adverse effects of the spatial electric field and inhibit dendrite growth. By theoretical calculations and experimental verification, layered double hydroxides (LDHs) materials were selected to immobilize SO 4 2- anions and construct a protective coating layer against anion depletion (anti-anionic-depletion layer). Furthermore, the deposition flux of Zn 2+ cations was also regulated by in-situ growing LDH nanosheets. Benefiting from these modifications, the in-situ grown ZnAl-LDH modified electrode (Zn@ZnAl) exhibits outstanding stability (5500 cycles at 40 mA cm −2 ), and shows negligible capacity degradation in both Zn-Mn full cells and zinc hybrid capacitors.

研究领域: 材料科学 · 电化学
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Small · 2025 · IF 12.1

ATP-Exhausted Strategy Induced Anti-Tumor Low-Temperature Photothermal Therapy Based on Rare Earth Nanocrystals Modified Hollow Porous MnOx Nanozyme with TME-Activated NIR-II Imaging

Xiaozhao Wang,Jing Li,Zhengtao Luo,Zhimin Gao,Yongxin Huang,Jiamin Luo,Xinyi Wang,Yaru Zhang,Meiling Tan,Zhiyao Hou

Insufficient adenosine triphosphate (ATP) can reduce the synthesis of heat-stress-induced heat shock proteins (HSPs) to promote the efficiency of mild photothermal therapy (mPTT), thus the rational design of ATP-exhausted strategy based on nanotechnology is an effective approach to resuscitate mPTT. Herein, Nd 3+ doped nanocrystals (NaYF 4 :Nd@CaF 2 , Nd-NCs) modified hollow mesoporous manganese oxide (H-MnO x ) nanocomposite (H-MnO x @Nd-NCs, MN) is synthesized, and loaded with glucose transporters (GLUTs) inhibitor KL-11743, noted as MN-KL nanozyme. In tumor microenvironment (TME), MN-KL can react with overexpressed glutathione (GSH) to release KL-11743, which can suppress the synthesis of intracellular ATP at the source by blocking glucose uptake to inhibit HSPs expression, meanwhile, MN-KL catalyzes the production of ·O 2 − / 1 O 2 /·OH and lipid peroxidation (LPO) to cleave existing HSPs. Through a two-pronged strategy with ATP inhibition and oxide accumulation, reducing the level of HSPs can be guaranteed for achieving efficient mPTT in both subcutaneous and in situ tumor models in mice. During this process, Nd-NCs can absorb near-infrared light and convert it into heat, and the quenched fluorescence of Nd-NCs by H-MnO x can be recovered through GSH-triggered biodegradation in tumors, thus the modification of Nd-NCs not only provides photothermal effect but also enables MN to own TME-activated fluorescence imaging.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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