MOLECULAR BIOLOGY REPORTS
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2025
·Vol. 53
·期 1
·82
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IF 2.8
Qi Xue,Hu Yanjun,Yang Jinghan,Jiang Mingxuan,Zhang Junhao,Du Yanting,Hu Changmin
Background The pathogenesis of bovine mastitis involves inflammation and cell death, with pyroptosis being a key factor in its development. Currently, antibiotics remain the primary therapeutic option for bovine mastitis, however, the increasing prevalence of antibiotic resistance constitutes a major public health threat. Selenium (Se) has been reported to alleviate inflammation primarily through its antioxidant properties, but the mechanism by which Se regulates pyroptosis in bovine mastitis remains unclear. Methods and results In this study, an in vitro mastitis model was established by infecting MAC-T cells with inactivated Staphylococcus aureus ( S. aureus ) (MOI = 10, 12 h). The results revealed that the mitochondrial membrane potential of the MAC-T cells in the infection group decreased significantly. Moreover, the accumulation of Reactive oxygen species (ROS) was accompanied by the activation of NOD-like receptor family containing pyrin domain 3 (NLRP3), the expression of the pyroptosis-related genes gasdermin D amino terminal fragment (GSDMD-N), and cysteine aspartate specific protease 1 (cleaved-caspase 1). Pretreatment with Se, the NLRP3 inhibitor MCC950 and the antioxidant N-acetylcysteine (NAC) attenuated mitochondrial damage, ROS accumulation, and the inhibition of pyroptosis. An in vivo mastitis model was established in mice fed a high-selenium diet (containing 1.5 mg/kg Se) and intramammarily injected with inactivated S. aureus (1 × 10 8 CFU/mL). Histological analysis revealed intact alveolar structure and reduced inflammatory cell infiltration in mice fed the high-selenium diet. The expression of the inflammasome NLRP3 downregulated, and the expression of GSDMD-N, a direct executor of pyroptosis, upregulated. Conclusion Our in vitro and in vivo results confirmed that Se alleviate mitochondrial damage and pyroptosis by inhibiting the NLRP3 pathway, ultimately alleviating mastitis. Graphical
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JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Manlin Qi,Yulin Xie,Jing Zhou,Chengyu Liu,Qihang Ding,Fanrou Zhang,Fangyu Shi,Biao Dong,Chunxia Li,Lin Wang
Chronic bacterial infections in diabetic wounds remain a major clinical challenge due to persistent inflammation, biofilm formation, and antibiotic resistance. Herein, we report a glucose-responsive cascade nanozyme system (PPCG) that functions as a microenvironment-adaptive reactive oxygen species (ROS) delivery platform for localized treatment of infected diabetic wounds. The PPCG integrates glucose oxidase (GOx) with a PdPtCu nanozyme core, enabling a triggered and self-sustaining catalytic cycle that amplifies ROS generation in glucose-rich infectious microenvironments while minimizing ROS release in glucose-deficient healthy tissue. GOx initiates the cascade by converting glucose into gluconic acid and H 2 O 2 . This locally generated H 2 O 2 is then transformed into hydroxyl radicals via peroxidase- and glutathione oxidase-like activities, while catalase-like activity decomposes excess H 2 O 2 into oxygen to reinforce the catalytic loop. Upon near-infrared-II laser irradiation, PPCG further enables synergistic photothermal disruption of bacterial biofilms. Multi-omics analyses revealed that PPCG triggers severe redox imbalance and metabolic stress, including impairing glucose uptake and glycolytic flux, triggering maladaptive carbon metabolic reprogramming, and ultimately resulting in ATP depletion and bacterial collapse. This spatiotemporally controlled ROS-generating platform represents a promising infection therapy that couples nanozyme cascade catalysis with metabolic targeting for enhanced bacterial eradication and minimal off-target effects.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Na Peng,Chun Song,Xiaoting Liu,Michał Nowicki,Roman Szewczyk,Yanyang Wang,Yi Liu
Tumor-associated macrophage (TAM) polarization is related to mitochondrial function, stability, and ROS production. The development of a mitochondria-targeted nanosystem with immunomodulatory impact on TAM repolarization is crucial for macrophage-targeted immunotherapy. First, zirconium(IV) coordinated with tetra-kis(4-caboxyphenyl) porphyrin to synthesize PCN-224, which encapsulated CO-releasing molecule 401 (CORM-401) via the hollow structures (PCN-CORM), and then, an amphiphilic copolymer containing triphenylphosphine (TPP) was synthesized to load PCN-CORM via self-assembly and surface-coated with hyaluronic acid (HA) to obtain the mitochondria-targeted nanosystem (HA@MR@PCN-CORM). Mediated by HA and TPP motifs, HA@MR@PCN-CORM efficiently targeted mitochondria of TAMs via HA-CD44 interaction and re-exposed TPP groups by digesting HA and caused reactive oxygen species (ROS) and carbon dioxide (CO) storm under a laser irradiation of 660 nm (20 mW cm–2), and the killing rate of M2-like TAMs reached 66.8% at a PCN-224 concentration of 15 μg/mL. Moreover, HA@MR@PCN-CORM, through depletion of GSH, inhibition of glutamine metabolism, and metabolic reprogramming, resulted in an increased ratio of M1/M2-type TAMs from 0.29 to 1.20 and an in vivo tumor volume inhibition rate of 93.4% with synergistically enhanced infiltration of CD3+/CD4+, CD3+/CD8+ T lymphocytes, and DCs in tumor tissues. The nanosystem was exhibited as a promising strategy for depletion and modulation of TAMs in an immunosuppressive tumor microenvironment for antitumor therapy.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Liyun Jie,He Huang,LuYing Sha,Lidan Zhang,Ye Wang,Yu Cao
Cutaneous squamous cell carcinoma (cSCC) is a common type of skin tumor with high incidence and significant disease burden. Current clinical treatments face challenges such as high recurrence rates and drug resistance, making the discovery of novel drugs and therapeutic targets critically important. Previous studies have confirmed that Mangiferin(MF) can inhibit the proliferation of various tumors, promote apoptosis, and regulate cellular oxidative stress. This study investigated the therapeutic effects and mechanisms of MF in cutaneous squamous cell carcinoma (cSCC). CCK-8 and EDU assays demonstrated that MF significantly inhibited A431 cell proliferation, induced apoptosis, and caused G0/G1 phase arrest. Network pharmacology, molecular docking, and molecular dynamics simulations identified HSP90α as a direct target of MF, which was highly expressed in clinical cSCC tissues and validated through CETSA and DARTS experiments. Genetic manipulation experiments revealed that HSP90α knockdown promoted apoptosis, while its overexpression accelerated proliferation and attenuated MF's effects. Mechanistically, MF induced ROS generation, leading to mitochondrial and DNA damage, which could be reversed by the antioxidant NAC. Furthermore, ROS-mediated activation of the MAPK pathway contributed to apoptosis and DNA damage. In vivo, MF effectively suppressed cSCC growth without causing organ toxicity. In conclusion, MF inhibits cSCC progression both in vitro and in vivo with minimal toxicity, primarily through targeting HSP90α and activating the ROS/MAPK pathway.
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JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Honggui Wang,Qi Dai,Yanhui Yin,Linjie Wang,Chenxi Li,Qingqing Sheng,Zhe Piao,Ya Zhang
The widespread dissemination of antibiotic resistance genes (ARGs) across the globe poses a growing and significant threat to both environmental and human health. Chlorinated paraffins (CPs) are extensively used worldwide and are increasingly detected across diverse environmental compartments. However, the impact of CPs on ARGs dissemination remains inadequately understood. This study systematically evaluates the effects of CPs (C10 - C30 mixture) with varying chlorination levels (CPs42, CPs52, CPs58) on ARGs spread in aquatic environments, utilizing a natural transformation (NT) model based on the plasmid pWH1274 and Acinetobacter baylyi ADP1. The results demonstrated that bacterial exposure to CPs induced the production of reactive oxygen species (ROS), which increased with rising CPs concentrations and chlorination levels. Lethality was observed at high CPs concentrations (e.g., 100 - 400 mg/L). Mechanistic investigations revealed that CPs-enhanced ARG dissemination primarily occurs through ROS-driven facilitation of natural transformation. Further analysis indicated this enhancement stems from ROS-mediated processes that elevated bacterial cellular competence and recombinational activity. Critically, our findings confirm that the risk of ARGs dissemination amplification escalates with increasing chlorination levels of CPs. This work advances our understanding of the environmental risks associated with CPs and provides crucial theoretical foundations for mitigating their detrimental effects.
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Biomolecules
·
2023
·Vol. 13
·期 10
·1464
·
IF 5.5
Xiaoyan Yuan,Junting Yang,Yuling Huang,Jia Li,Yuanyuan Li
There has been a growing interest in studying the communication of gut microbial metabolites between the gut and the liver as liver fibrosis progresses. Although 3-Indolepropionic acid (IPA) is regarded as a clinically valuable gut metabolite for the treatment of certain chronic diseases, the effects of oral administration of IPA on hepatic fibrosis in different animal models have been conflicting. While some mechanisms have been proposed to explain these contradictory effects, the direct impact of IPA on hepatic fibrosis remains unclear. In this study, we found that IPA could directly activate LX-2 human hepatic stellate cells in vitro. IPA upregulated the expression of fibrogenic marker genes and promoted the features associated with HSCs activation, including proliferation and contractility. IPA also increased reactive oxygen species (ROS) in mitochondria and the expression of inflammation-related genes in LX-2 cells. However, when a ROS-blocking agent was used, these effects were reduced. p38 and JNK, the downstream signaling cascades of ROS, were found to be required for the activation of LX-2 induced by IPA. These findings suggest that IPA can directly activate hepatic stellate cells through ROS-induced JNK and p38 signaling pathways.Keywords:gut–liver axis;3-Indolepropionic acid;HSCs;liver fibrosis
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BIOMATERIALS
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2018
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IF 8.806
Jie Li,Chunyang Sun,Wei Tao,Ziyang Cao,Haisheng Qian,Xianzhu Yang,Jun Wang
Controlling poly(ethylene glycol) (PEG) shielding/deshielding at the desired site of action exhibits great advantages for nanocarrier-based on-demand drug delivery in vivo . However, the current PEG deshielding strategies were mainly designed for anticancer drug delivery; even so, their applications are also limited by tumor heterogeneity. As a proof-of-concept, we explored a photoinduced PEG deshielding nanocarrier TK-NP Ce6&PTX to circumvent the aforementioned challenge. The TK-NP Ce6&PTX encapsulating chlorin e6 (Ce6) and paclitaxel (PTX) was self-assembled from an innovative thioketal (TK) linkage-bridged diblock copolymer of PEG with poly(d, l -lactic acid) (PEG- TK -PLA). We demonstrated that the high PEGylation of TK-NP Ce6&PTX in blood helps the nanocarrier efficiently avoid rapid clearance and consequently prolongs its circulation time . At the desired site (tumor), 660-nm red light irradiation led to ROS generation in situ , which readily cleaved the TK linkage, resulting in PEG deshielding. Such photoinduced PEG deshielding at the desired site significantly enhances the cellular uptake of the nanocarriers, achieving on-demand drug delivery and superior therapeutic efficacy. More importantly, this strategy of photoinducing PEG deshielding of nanocarriers could potentially extend to a variety of therapeutic agents beyond anticancer drugs for on-demand delivery.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Yufei Cao,Mingsheng Liu,Ju Cheng,Juanjuan Yin,Congshu Huang,Haiyan Cui,Xiangdong Zhang,Guanghui Zhao
Nitric oxide (NO) gas therapy has aroused intense interest in recent years. l-Arginine (l-Arg) reacts with reactive oxygen species (ROS) in tumor cells to generate NO. This phenomenon represents an effective method for tumor therapy. However, endogenous ROS levels in most types of tumor cells cannot enable an effective reaction. β-Lapachone is generally used to increase H2O2, which can oxidize guanidine derivatives to form nitric oxide in tumor cells. In addition, based on the ferrocene (Fc)-catalyzed Fenton reaction, ·OH is generated from H2O2, and the ONOO– could be generated from an interaction between ·O2– (generated through the Haber–Weiss reaction) and NO. Arg-rich poly(ε-caprolactone) (PCL)-b-PArg, a macromolecular NO donor, was accurately synthesized to avoid premature l-Arg leakage during in vivo transport. In this design, the self-assembled PCL-b-PArg nanoparticles were dressed with the tumor-shreddable masking (PEG-b-PDMA, a negatively charged pH-sensitive hydrophilic diblock polymer), to prepare P-lapa-Fc nanoparticles and hide penetrative capability in the circulation. The experimental results confirmed that this synergistic therapy based on ROS and NO had a significant inhibitory effect on cancer cells, thereby providing new inspiration for NO gas treatment.
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Advanced Healthcare Materials
·
2021
·Vol. 11
·期 4
·2101855
·
IF 9.933
Jieqi Xie,Yuejun Yao,Shuqin Wang,Linge Fan,Jie Ding,Yun Gao,Shifen Li,Liyin Shen,Yang Zhu,Changyou Gao
Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch. Inflammation and fibrosis are also reduced in the PFTU/gelatin-treated hearts, resulting in the reduced left ventricular remodeling and better cardiac functions postimplantation for 28 d.
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JOURNAL OF DRUG TARGETING
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2020
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IF 3.38
Peng Ji,Le Wang,Siqi Wang,Yongxin Zhang,Xiaole Qi,Juan Tao,Zhenghong Wu
Artesunate (AS), as an effective new tumour treatment drug, induces cancer cell death based on high intracellular reactive oxygen species (ROS) produced by interacting with ferrous ions. However, the relatively low intracellular ferrous iron ion concentrations and the low efficiency of ROS generation limit its clinical application. Herein, we developed a metal-organic framework-Fe2+ (MOF), and AS was loaded in the MOF and then coated with hyaluronic acid (HA) on the surface of the MOF (HA@MOF-AS) for targeted and enhanced cancer treatment. HA@MOF-AS has high loading efficiency, good monodispersity, biocompatibility, strong cell uptake capacity and high intracellular ROS production, and it can target tumour tissues. In addition, in vivo anticancer studies have shown that HA@MOF-AS not only has high accumulation in tumours but also significantly inhibits tumour growth without significant damage to major organs. Therefore, HA@MOF-AS has excellent potential and may open a new approach for targeted cancer treatment.
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SENSORS AND ACTUATORS B-CHEMICAL
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2023
·
IF 8.4
Shen Wang,Yingyong Ni,Junjun Wang,Yingcui Bu,Yuxin Yang,Xianshun Sun,Xiaojiao Zhu,Lin Kong,Sen Wang,Hongping Zhou
Lipid droplets (LDs) have attracted much attention due to their unique structure and key connections with various organelles in cells. Here, we constructed a reactive oxygen species (ROS) -generating system by carefully designing photosensitizers ( TT2CN ) with proper lipophilicity , excellent light stability and cell imaging ability. In detail, TT2CN can selectively accumulate into LDs (as carriers for TT2CN ) and then a subcellular photo-inducible ROS-generating system was formed. Confocal fluorescence imaging revealed the contact behavior of dynamic LDs with other organelles in the cells and the photo-produced ROS can induce multiple organelle damages. Flow cytometry , AM / PI and 3D multicellular tumor spheres (3D MCTs) experiments further verified and demonstrated its promising biological application . This work not only uncovers the communication behavior between LDs and other organelles, but also provides a new anticancer strategy of LDs-mediated photodynamic therapy.
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MOLECULES
·
2024
·Vol. 29
·期 8
·1845
·
IF 4.2
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.
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