CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Shuangshuang Chen,Zelin Sang,Yumei Li,Hui Li,Zhenhua Chen,Xifan Mei,Xianbing Dai,Xiuli Ren
Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system. How to effectively deliver drugs to the site of spinal cord injury lesions through the blood spinal cord brain barrier (BSCB) has always been a challenge. There is an urgent need for developing a controllable and effective method to continuously release drug for SCI repair. Microneedles are a promising drug delivery method, however, how to control drug release smartly from microneedles remains a cutting-edge field. Herein, a NIR triggered photothermal responsive microneedles patch with Au@polyphenol nanospheres encapsulated was designed for SCI repair. By regulating the NIR irradiation, the thermal swelling rate of the microneedles can be precisely controlled. Therefore, the releasing of Au@polyphenol nanospheres from the microneedles could be controlled. Gold nanoparticles are known as nanozyme in photothermal therapy. Polyphenol nanospheres released from microneedles are helpful in promoting spinal cord injury repair by modulating mitochondrial ROS microenvironment. This NIR responsive microneedles array patch loaded with gold@polyphenol nanospheres has the advantages of effectively clearing reactive oxygen species, promoting mitochondrial autophagy, rebuilding redox balance, and reducing neuronal apoptosis.
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Plants-Basel
·
2023
·Vol. 12
·期 4
·940
·
IF 4.5
Youmei Huang,Xinpeng Xi,Mengnan Chai,Suzhuo Ma,Han Su,Kaichuang Liu,Fengjiao Wang,Wenhui Zhu,Yanhui Liu,Yuan Qin,Hanyang Cai
Reactive oxygen species (ROS), a type of oxygen monoelectronic reduction product, play integral roles in root growth and development. The epigenetic mechanism plays a critical role in gene transcription and expression; however, its regulation of ROS metabolism in root development is still limited. We found that the chromatin remodeling complex SWR1 regulates root length and lateral root formation inArabidopsis. Our transcriptome results and gene ontology (GO) enrichment analysis showed that the oxidoreductase activity-related genes significantly changed in mutants for theArabidopsisSWR1 complex components, such asarp6andpie1, and histone variant H2A.Z triple mutanthta8 hta9 hta11.The three encoding genes inArabidopsisare the three H2A.Z variantshta8,hta9, andhta11. Histochemical assays revealed that the SWR1 complex affects ROS accumulation in roots. Furthermore, chromatin immunoprecipitation quantitative real-time PCR (ChIP-qPCR) analysis showed that the reduced H2A.Z deposition in oxidoreductase activity-related genes caused ROS to accumulate inarp6,pie1, andhta8 hta9 hta11. H2A.Z deposition-deficient mutants decreased after the trimethylation of lysine 4 on histone H3 (H3K4me3) modifications and RNA polymerase II (Pol II) enrichment, and increased after the trimethylation of lysine 27 on histone H3 (H3K27me3) modifications, which may account for the expression change in oxidoreductase activity-related genes. In summary, our results revealed that the chromatin complex SWR1 regulates ROS accumulation in root development, highlighting the critical role of epigenetic mechanisms.Keywords:ROS;root;SWR1;Arabidopsis;H2A.Z;oxidoreductase activity-related genes
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REPRODUCTIVE TOXICOLOGY
·
2021
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IF 3.143
Yingying Zhang,Jiaqi Tang,Na Li,Jianying Tao,Yan Zhang,Yumeng Zhang,Yang Ye,Qiutong Zheng,Ting Xu,Yanping Liu,Pengjie Zhang,Lingjun Li,Huan Li,Yun He,Hongyu Su,Qinyuan He,Miao Sun,Zhice Xu
Pulmonary arterial hypertension is a progressive disorder characterized by remodeling and increased small pulmonary arteries resistance. Endothelin-1 (ET-1) was related to PAH and ET-1 receptors were up-regulated selectively in the lung when exposed to toxic factor hypoxia. However, the role of ET-1 signaling in the pathogenesis of prenatal hypoxia-induced pulmonary abnormalities remains to be elucidated. Pregnant rats were divided into prenatal hypoxia (10.5 % O 2 from gestational day 4–21) and control group. Their three-month-old offspring male rats were tested for vascular functions and molecular analysis, DNA methylation was assessed for cellular hypoxia. Functional testing showed that ET-1-mediated vasoconstriction was enhanced, and the expressions of endothelin A receptor/B receptor (ET A R/ET B R), inositol 1,4,5-trisphosphate receptor, type 1, and the sensitivity of calcium channels were increased in the small pulmonary arteries following prenatal hypoxia. q-PCR and DHE staining showed that the expressions of NADPH oxidase 1/4 (Nox1/4) were up-regulated, along with the increased production of superoxide anion. Furthermore, superoxide anion promoted ET-1-mediated pulmonary artery contraction. In the pulmonary artery smooth muscle cell experiments, q-PCR, Western Blot, CCK8 and DHE staining showed that the expressions of ET B R, Nox1/4, and superoxide anion were increased by hypoxia, along with promoted cell proliferation. 2,2,6,6-Tetramethyl-1-piperidinyloxy reversed hypoxia-induced cell proliferation. ET B R antagonist BQ788 inhibited hypoxia-increased expressions of Nox1/4, superoxide anion production, and proliferation of cells. Moreover, methylation analysis indicated that hypoxia decreased the methylation levels of the ET B R promoter in the pulmonary artery smooth muscle cells. The results indicated that prenatal toxic factor hypoxia resulted in abnormal ET B R activation, which enhanced ET-1-mediated vasoconstriction of pulmonary arteries and pulmonary artery smooth muscle cell proliferation through ET B R/Nox1/4-derived ROS pathway.
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Acta Biomaterialia
·
2025
·
IF 9.6
Chaorong Wei,Lingke Feng,Jing Liu,Mingxia Xu,Yongsheng Cui,Fengyi Lin,Honglian Yu,Zhanzhan Feng,Hong Zhang,Changyang Gong,Peng Mi
X-ray-induced photodynamic therapy (X-PDT) shows significant promise in tumor treatments due to its unlimited tissue penetration but requires delivering sensitizers to tumors. Here, we engineered photosensitizer verteporfin (VP) and T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor OTS964-encapsulated polymeric nanocarriers (VP/OTS964@NPs) for effective tumor X-PDT, molecule-targeted therapy and inducing robust antitumor immunity for synergistic immunotherapy of low immunogenic breast tumors and their lung metastases when combined with PD-L1 blockade. The VP/OTS964@NPs are monodisperse and can be disassembled to release drugs in response to high reactive oxygen species (ROS) levels in the tumor microenvironment or generated during X-PDT. It can efficiently deliver drugs into the TOPK-high expression breast cancer cells, generate ROS and induce ICD effects. By i.v. injection, VP/OTS964@NPs efficiently accumulated in the breast tumors and effectively eradicated tumors upon X-PDT. Additionally, the VP/OTS964@NPs activated the systemic antitumor immune responses, significantly inhibited the distant breast tumors and the lung metastasis of breast tumors, and enhanced the survival rates in combination with PD-L1 blockade. This study presented a strategy for engineering nanocarriers for synergistic molecular therapy, tumor XDT and immunotherapy. Statement of Significance X-PDT is a promising therapeutic modality for cancer treatment. However, its clinical application is hindered by the limited availability of suitable sensitizers and their insufficient tumor-targeting capability. This work aims to construct ROS-sensitive nanocarriers co-loaded with the photosensitizer verteporfin and the TOPK inhibitor OTS964 to achieve synergistic X-PDT for triple-negative breast cancer. By further activating antitumor immune responses, this strategy is designed to suppress the distant and metastatic breast tumors. Overall, this work provides both a nanodrug platform and a therapeutic strategy for the treatment of poorly immunogenic solid tumors.
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Advanced Healthcare Materials
·
2025
·Vol. 15
·期 3
·e00355
·
IF 9.6
Xin Liu,Shaopeng Liu,Bo Ma,Yang Zhang,Qianxiang Meng,Mingyue Chen,Fangye Chen,Miaomiao Tian,Song Liu,Peng Liu,Kaiyong Cai
Photothermal therapy (PTT) in antimicrobial treatment of diabetic wounds faces the challenge of damaging normal tissues with high temperatures. In this study, mesoporous polydopamine (MPDA) as the core, encapsulated by Zeolitic Imidazolate Framework-8 (ZIF-8) shell, and loaded with berberine (BBR) are used to fabricate MPDA@ZIF-8/BBR core–shell nanoparticles (NPs). Then, those NPs are incorporated into hydrogels formed by reacting carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) via Schiff base chemistry, creating a photothermal nanocomposite hydrogel capable of scavenging ROS (Gel- MPDA@ZIF-8/BBR). The hydrogel achieves low-temperature PTT antimicrobial activity by controlled degradation under the weak acidic conditions of the bacterial infection microenvironment and simultaneous release of BBR and Zn 2 ⁺, combined with the mild photothermal effect of MPDA. The released BBR synergistically enhances the photothermal effect by inhibiting bacterial community sensing, effectively disintegrating the bacterial biofilm. More importantly, the composite hydrogels showed good biocompatibility, effectively inhibited the wound inflammatory response, and significantly accelerated wound healing, which achieved low-temperature PTT antibacterial therapy and has the potential to treat diabetic-infected chronic wounds.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Wenjia Xie,Yuxuan Wang,Jicenyuan Wu,Xu Wang,Jiaxin Wu,Bin Cheng,Hao Feng,Xinxu Huang,Xinting Cheng,Junyu Chen,Qianbing Wan,Jian Wang,Xibo Pei
Diabetic periodontitis is characterized by persistent and aggravated inflammation, largely driven by a reactive oxygen species (ROS) vicious loop in M1 macrophages driven by mitochondrial dysfunction. To disrupt this pathogenic cascade, we developed hierarchically targeted polymeric nanoparticles (MPPT NPs) by conjugating the tuftsin peptide for selective uptake by M1 macrophages and loading mitoquinone mesylate (MitoQ) to restore mitochondrial function after mitochondrial localization. For local retention and responsive drug release, MPPT NPs were incorporated into a ROS-responsive hydrogel (MTP hydrogel) constructed by cross-linking poly(vinyl alcohol) (PVA) with a ROS-cleavable linker (N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1,3-diaminium (TSPBA)). This constructed platform not only enabled the on-demand release of MPPT NPs but also provided additional ROS-scavenging ability. In vitro studies demonstrated that MTTP NPs effectively repaired oxidatively damaged mitochondria and suppressed NLRP3 inflammasome priming and activation. MTP hydrogel platform reduced pro-inflammatory cytokine release and rescued inflammation-induced osteogenic impairment. In a diabetic periodontitis rat model, local administration of the MTP hydrogel significantly attenuated periodontal tissue destruction and promoted alveolar bone regeneration, achieving BV/TV 1.5 times that of previous reports. Collectively, this hierarchically targeted and ROS-responsive platform disrupts the ROS vicious loop in M1 macrophages by repairing damaged mitochondria, offering a promising therapeutic strategy for the management of diabetic periodontitis.
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Gao Chengcheng,Sun Xin,Wu Zhipan,Yuan Huahua,Han Haote,Huang Hongliang,Shu Yuhan,Xu Mengting,Gao Ruilan,Li Shouxin,Zhang Jianbin,Tian Jingkui
Introduction: The leaves of Morus alba L is a traditional Chinese medicine widely applied in lung diseases. Moracin N (MAN), a secondary metabolite extracted form the leaves of Morus alba L, is a potent anticancer agent. But its molecular mechanism remains unveiled.Objective: In this study, we aimed to examine the effect of MAN on human lung cancer and reveal the underlying molecular mechanism.Methods: MTT assay was conducted to measure cell viability. Annexin V-FITC/PI staining was used to detect cell apoptosis. Confocal microscope was performed to determine the formation of autophagosomes and autolysosomes. Flow cytometry was performed to quantify cell death. Western blotting was used to determine the related-signaling pathway.Results: In the present study, we demonstrated for the first time that MAN inhibitd cell proliferation and induced cell apoptosis in human non-small-cell lung carcinoma (NSCLC) cells. We found that MAN treatment dysregulated mitochondrial function and led to mitochondrial apoptosis in A549 and PC9 cells. Meanwhile, MAN enhanced autophagy flux by the increase of autophagosome formation, the fusion of autophagsomes and lysosomes and lysosomal function. Moreover, mTOR signaling pathway, a classical pathway regualting autophagy, was inhibited by MAN in a time- and dose-dependent mannner, resulting in autophagy induction. Interestingly, autophagy inhibition by CQ or Atg5 knockdown attenuated cell apoptosis by MAN, indicating that autophagy serves as cell death. Furthermore, autophagy-mediated cell death by MAN can be blocked by reactive oxygen species (ROS) scavenger NAC, indicating that ROS accumulation is the inducing factor of apoptosis and autophagy. In summary, we revealed the molecular mechanism of MAN against lung cancer through apoptosis and autophagy, suggesting that MAN might be a novel therapeutic agent for NSCLC treatment.
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INFLAMMATION RESEARCH
·
2014
·Vol. 63
·期 7
·597-608
·
IF 2.143
Pan Xiaolong,Cao Xiang,Li Na,Xu Yimiao,Wu Qiuyue,Bai Jing,Yin Zhimin,Luo Lan,Lan Lei
Objective Forsythin (FOR) is an active ingredient extracted from the fruit of the medicinal plant Forsythia suspensa (Thunb.) Vahl. Here, we investigated the effect of FOR on LPS-induced inflammatory response and the underlying molecular mechanisms in RAW264.7 macrophages. Materials and methods RAW264.7 cells were pre-treated with or without FOR and then stimulated with or without LPS. The productions of TNF-α, IL-1β, IL-6, PGE 2 and NO were determined by ELISA and nitrite analysis, respectively. The expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were measured by Western blotting and RT-PCR analysis. The activations of signaling molecules were detected by Western blotting using phosphorylation specific antibodies. Reactive oxygen species (ROS) production was determined by ROS assay. Results LPS-induced productions of IL-1β, IL-6, TNF-α, NO and PGE 2 were inhibited by FOR in a dose-dependent manner. FOR also suppressed the LPS-elevated expressions of iNOS and COX-2. Further investigations revealed that FOR significantly inhibited the LPS-induced activations of JAK-STATs and p38 MAPKs, but not of IKKα/β in LPS-stimulated RAW264.7 cells. Additionally, FOR interfered with both JAK-STATs and p38 MAPKs signaling pathways to modulate the expressions of IL-1β, IL-6, TNF-α, iNOS and COX-2. Furthermore, FOR reduced the LPS-induced ROS accumulation, validating that FOR serves as an antioxidant. Conclusions Our data suggested that FOR exerts anti-inflammatory action, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signalings and production of ROS in macrophage cells.
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CARBOHYDRATE POLYMERS
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2025
·
IF 12.5
Mingxiao Shao,Yan Peng,Liyan Qiu
Oxidative stress-mediated tumor therapy leverages reactive oxygen species (ROS) for cancer treatment, but protective autophagy, a major survival pathway for tumor cells, causes therapy resistance. Herein, a self-amplifying ROS-responsive nanovesicle system (CQ/Cu@CT) is designed to enhance oxidative stress while blocking autophagy. Firstly, amphiphilic oligochitosan derivative COS-PEG2KTA-UB is synthesized, where ROS-responsive thioketal acetal (TA) is introduced in form of cinnamaldehyde (CA) prodrug. This polymer self-assembles into nanovesicles, integrating chloroquine (CQ) and supplemental TA to immobilize Cu 2+ via carboxylic coordination. Intracellular ROS triggers nanovesicle dissociation to release CA, Cu 2+ , and CQ. CA induces mitochondrial dysfunction and ROS burst, while Cu 2+ depletes glutathione and generates Cu + for Fenton-like reactions to produce hydroxyl radicals. Meanwhile, due to the inhibition effect of CQ on protective autophagy, CQ/Cu@CT produces significantly high ROS level. The amplified ROS not only aggravates oxidative stress but also accelerates drug release from nanovesicles, which facilitates the drug action against tumors. CQ/Cu@CT also induces immunogenic cell death (ICD) to stimulate dendritic cell maturation and enhance cytotoxic T lymphocyte infiltration. Consequently, CQ/Cu@CT inhibits tumor growth by 67.8 % in a subcutaneous 4 T1 tumor model. This study provides a potent strategy to enhance oxidative stress-based cancer therapy.
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Nano Today
·
2025
·
IF 10.9
Pengchen Wang,Jintong Na,Xiyu Liu,Minhui Cui,Ganghao Liang,Xinyue He,Haihua Xiao,Yongxiang Zhao,Yuan Liao,Liping Zhong
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by low immune response rates and high recurrence. This underscores an urgent need for more effective treatment strategies for liver cancer patients. Ferroptosis, a type of cell death associated with iron-dependent lipid peroxidation, has shown significant potential in HCC treatment. However, the efficacy of this monotherapy for tumor treatment remains limited. Enhancing reactive oxygen species (ROS) accumulation and lipid peroxide formation by inhibiting the tumor cell antioxidant system has emerged as a promising anti-tumor strategy. In this study, we developed a nanoplatform, NP (nanoparticle)-BSD@WFR, specifically tailored for HCC treatment. This system combines a biodegradable sonodynamic polymer (BSD) with warfarin (WFR), a VKORC1L1 inhibitor that prevents intracellular peroxide elimination and enhances ferroptosis. Under ultrasound irradiation, NP-BSD@WFR generates ROS and releases WFR, directly targeting cancer cells. Concurrently, ROS and WFR synergistically enhance lipid peroxide production in cancer cells, triggering ferroptosis and activating the immune system. Animal studies further demonstrate that combining sonodynamic therapy with WFR-induced ferroptosis produces a synergistic anti-tumor effect, promoting a strong immune response in vivo. This study introduces an innovative therapeutic approach combining sonodynamic therapy and WFR for HCC treatment and highlights its promising efficacy.
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NEUROCHEMISTRY INTERNATIONAL
·
2025
·
IF 4
Yinpei Huang,Hailun Xie,Lian Liu,Heng Zhao,Bing Li,Feng Zhang
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (IH), which induces oxidative stress and neuronal apoptosis, ultimately leading to progressive cognitive impairment. This study investigated the neuroprotective potential of a reactive oxygen species (ROS)-responsive nanotherapeutic, namely TPCD nanoparticles (TPCD NP), synthesized through the conjugation of Tempol and phenylboronic acid pinacol ester to β-cyclodextrin, in both in vivo and in vitro models. In rats, intravenous administration of TPCD NP improved memory performance as assessed by the Morris water maze test, and preserved hippocampal neuronal morphology. TPCD NP significantly reduced intracellular ROS content and malondialdehyde (MDA) levels while restoring antioxidant capacity, including superoxide dismutase (SOD) and glutathione (GSH). Apoptosis was attenuated, as evidenced by the downregulation of Bax and cleaved caspase-3, and the upregulation of Bcl-2 expression. Mechanistically, TPCD NP enhanced the nuclear translocation of nuclear factor erythroid 2–related factor 2 (NRF2), suppressed Kelch-like ECH-associated protein 1 (KEAP1), and increased heme oxygenase-1 (HO-1) expression. The protective effects were abolished by ML385, a selective NRF2 inhibitor, confirming the essential role of NRF2 activation in mediating the antioxidant and anti-apoptotic effects of TPCD NP. In conclusion, TPCD NP attenuates oxidative stress and apoptosis induced by IH in the hippocampus by activating the NRF2/KEAP1/HO-1 pathway. These findings highlight TPCD NP as a promising therapeutic strategy for OSA-associated neurodegeneration.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Danya Zhang,Peilin Zhuang,Yunyi Wang,Bingxu Lu,Jiajia Linghu,Yaping Yin,Baohan Xie,Guichao Zhang,Qin Mao,Zhaoqiang Zhang
The clinical management of chemotherapy-induced oral mucositis (CIOM) remains a clinical challenge, primarily due to the moist and mechanically dynamic environment, which limits the adhesion and retention of conventional wound dressings. To address these clinical challenges, we designed a dynamic wet-adhesive hydrogel named AC-PEG-ALIP, which is composed of four-arm polyethylene glycol succinimidyl ester (Tetra-PEG-SS), amino-modified recombinant human type III collagen (rhCOL3-NH 2 ) and reactive oxygen species (ROS)-responsive Alkannin-encapsulated liposomes (Lip@Alk). The AC-PEG-ALIP hydrogel exhibited multiple therapeutic activities, including potent anti-inflammatory activity, robust antioxidant capacity, tissue-repair potential, and anti-senescent effects. Material characterization demonstrated that the material exhibited strong wet adhesion, with a maximum adhesion stretch of 160 kPa, sustained-release drug, and excellent biocompatibility. In vitro assessments confirmed the hydrogel's excellent biocompatibility. AC-PEG-ALIP enhanced HOK cell migration, achieving 75% wound closure at 24 h, and significantly decreased the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) and NF-κB by 50-70%. In vivo, AC-PEG-ALIP significantly accelerated wound healing in a rat CIOM model, reducing residual wound area to 11.03% on day 7 versus 61.41% in untreated controls. Histological analyses further revealed enhanced collagen deposition and a 2-fold increase in angiogenesis on day 3. In conclusion, the dynamic wet-adhesive hydrogel AC-PEG-ALIP provides a promising strategy for CIOM, highlighting the role of bio-interface design in mucosal drug delivery.
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