CARBOHYDRATE POLYMERS
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2020
·
IF 7.182
Jin Wang,Lehao Zhou,Qihao Sun,Haibo Cai,Wen-Song Tan
The proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) needed to be promoted for their use in stem cell-based therapy for large bone defects. This study aimed to prepare porous 2a-2 g scaffolds with antioxidant activity to reduce intracellular reactive oxygen species (ROS), which resulted in promoting the proliferation and osteogenic differentiation of MSCs. A series of novel chemically modified 2a-2 g scaffolds were fabricated by an acid-soluble/alkali-insoluble method. Besides, these 2a-2 g scaffolds had good biocompatibility, physicochemical properties and the ability to promote osteogenic differentiation of human adipose-derived stem cells ( h ADSCs). However, the proliferation ability of h ADSCs on 2a-2f scaffolds was weakened. Interestingly, 2 g scaffold had a positive effect on h ADSCs proliferation. These results indicated that the reduction of intracellular ROS was not conducive to h ADSCs proliferation but beneficial to h ADSCs osteogenic differentiation. Taken together, these significant results highlighted potential therapeutic benefit of 2 g scaffold in large bone defects.
研究领域:
生物材料
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干细胞研究
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组织工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 15
·3401-3411
·
IF 6.331
Ming Wang,Miao Li,Yunli Wang,Yiran Shao,Yingchun Zhu,Shiping Yang
Hydroxyapatite (HA) has attracted wide attention for medical application due to its biocompatibility and bioactivity. However, the infection problems of HA remain among the leading reasons for implantation failure. Thus, it is urgent to endow HA biomaterials with antibacterial activity. Herein, the high antibacterial activity was achieved by introducing trace Mn3+ and H vacancy couples in HA through a facile heat-treatment strategy in air. The theoretical results indicated that Mn3+ was preferentially substituted for the Ca(2) site in the HA structure with a charge-compensating H vacancy appearing at the adjacent OH− site. The antibacterial tests showed that Mn-HA possessed antibacterial activity towards both E. coli and S. aureus with trace Mn content at the ppm level, and implied that Mn3+ and centers may play an important role in the antibacterial process. The Mn3+ and couples in Mn-HA, serving as oxidative and reductive centers respectively, could then collectively participate in the CoQ/CoQH2 redox cycling and synergistically facilitate the accumulation of CoQ˙− and ROS radicals. This enhanced ROS production was the main factor to endow Mn-HA with efficient antibacterial activity. Moreover, the in vitro bioactivity assay showed that Mn-HA materials exhibited enhanced osteogenic activity and good biocompatibility. Therefore, this work not only provides a feasible method to control the oxidation state of Mn elements in HA, but also proposes a novel trace Mn3+-doped HA for potential applications in tissue engineering.
研究领域:
材料科学
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生物材料
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生物医学工程
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PubMed
高影响因子
TOXICOLOGY
·
2022
·
IF 4.571
Peng Lin,Xu Tong,Fan Xue,Chi Qianru,Tang Xinyu,Li Zhe,Bai Zhikun,Li Shu
Polystyrene nanoplastics (PS NPs) contamination is a serious problem for human and animal health. Excessive exposure to PS NPs can affect the structure and function of the heart. And lipopolysaccharide (LPS) induces myocardial damage , leading to myocardial fibrosis (MF). To investigate whether PS NPs exacerbate LPS-induced myocardial autophagy and fibrosis , we established in vivo and in vitro models of PS NPs/LPS exposure alone and in combination. We found that PS NPs/LPS exposure disrupts myocardial structure, significantly increases reactive oxygen species (ROS), triggers oxidative stress , promotes TGF-β1/Smad pathway activation, and leads to elevated levels of fibrotic proteins and collagen. Meanwhile, activation of AMPK/mTOR/ULK1 signaling pathway induced autophagy onset, and combined exposure of PS NPs/LPS exacerbated MF and autophagy. H9C2 cells were used for in vitro experiments, and the experimental results showed that the addition of TGF-β receptor inhibitor LY2109761 to the exposed group not only inhibited the upregulation of fibrotic genes but also effectively reduced the expression of autophagic signals, indicating that combined exposure of PS NPs and LPS mediates and regulates cardiac autophagy through TGF-β1. The above results suggest that PS NPs exacerbate LPS-induced MF and autophagy in mice via ROS/TGF-β1/Smad. Our study provides some new evidence to clarify the potential mechanisms of PS NPs-induced cardiotoxicity.
研究领域:
毒理学
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心脏病学
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纳米技术
·
细胞生物学
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DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2021
·
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.
研究领域:
药理学
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生理学
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分子生物学
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心血管疾病
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DOI
PubMed
高影响因子
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
研究领域:
植物生物学
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表观遗传学
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分子遗传学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2026
·
IF 7.8
Yan Shi,Jinrui Li,Jiaxuan Zhao,Lu Liu,Ruimin Zhan,Dandan Jing,Xiaoya Wang,Dongwei Ma,Junmin Lee,Zhiguo Wang,Ming Kong
Pathological scars are fibrotic disorders arising from aberrant wound healing. PDT is effective but limited by a dense matrix, hypoxia, and post-PDT excessive ROS-induced secondary inflammation. To address this, a NIR-switchable ROS-regulatory liposome (ICC@Lip) with CaO2 NPs (oxygenation to strengthen PDT) and Cu5.4O nanozymes (ROS scavenging) was developed. In addition, inspired by Cyperaceae stems and triangular arrows, a highly penetrable biomimetic microneedle platform loaded with ICC@Lip and collagenase I (ICC@Lip/HPMN) was constructed to realize efficient transdermal cargo delivery and diffusion into a rigid pathological scar matrix. The puncture resistance of ICC@Lip/HPMN was only 56.4% that of conventional rectangular pyramid microneedles, with an effective puncture rate of 96% in mouse skin. In vitro, under NIR irradiation-mediated PDT/PTT, ICC@Lip significantly alleviated intracellular hypoxia and related fibrotic indicators, achieving a cytotoxicity rate of 93.71% against myofibroblasts─1.49-fold higher than that of the IR808 alone group (62.74%)─while reducing M2 macrophage polarization and TGF-β secretion. Notably, timely post-PDT ROS clearance decreased M1 polarization of macrophages and reduced the release of over 50% of inflammatory cytokines. In rabbit ear, a hypertrophic scar model exhibited that ICC@Lip/HPMN reduced the scar elevation index from 3 to 1.7, significantly alleviating collagen deposition and inflammation. The antifibrotic efficacies were majorly exerted through cross-downregulation of TGF-β, IL-4, and toll-like receptor signaling pathways. This study provided a promising adaptive therapeutic strategy of self-strengthened PDT coupling ROS precise regulation for pathological scars.
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产品关联
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Xinyu Tan,Man Li,Zhibin Lan,Wenxiang Zhang,Junjie Zou,Yibo An,Jingwen Zheng,Xuwen Xiang,Jing Lin,Sheng Lin,Wenjie Ni,Lin Che,Gang Liu,Jing Chen,Zhixiang Lu
To address the intertwined pathologies of oxidative stress, immune dysregulation, and lipid metabolic disorders in acute liver injury (ALI), we engineered an innovative nanosystem: M2@SAM-F21. M2@SAM-F21 features an M2 macrophage membrane coating encapsulating diselenide-bridged mesoporous silica nanoparticles for silymarin and FGF21 plasmid DNA codelivery, enabling synergistic multidimensional treatment. First, reactive oxygen species (ROS)-responsive oxidative stress is mitigated. Diselenide bonds undergo ROS-triggered cleavage, achieving precise silymarin release that efficiently scavenges multiple ROS types, significantly mitigating hepatic oxidative damage. Simultaneously, FGF21 drives immune reprogramming. Efficiently expressed FGF21 protein drives macrophage polarization toward the M2 anti-inflammatory phenotype, effectively reducing proinflammatory cytokine levels, with TNF- α decreased to 61 pg/mL and IL-6 reduced to 20 pg/mL, while increasing IL-10 to 68 pg/mL to reverse the immune microenvironment imbalance. In addition, metabolic homeostasis is restored. Activated fatty acid oxidation pathways substantially decrease serum concentrations of total cholesterol (TC) to 4.984 mmol/L and triglycerides (TG) to 0.586 mmol/L, and almost reduce hepatocellular lipid droplet accumulation by 76%, resolving metabolic dysregulation. In both alcoholic and drug-induced ALI models, M2@SAM-F21 demonstrates exceptional hepatoprotection. For example, it significantly restores serum alanine aminotransferase (ALT) to 46.6 U/L and aminotransferase (AST) to 180 U/L in the alcoholic ALI model, while markedly alleviating histopathological vacuolization and steatosis, with biological distribution imaging confirming inflammation-targeted accumulation and proteomic analysis further elucidating therapeutic mechanisms. Exhibiting superior biosafety and dual therapeutic-prophylactic potential, this system serves as a pioneering paradigm that integrates targeted delivery, intelligent release, and multipathway synergy for ALI treatment.
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DOI
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 6
·722
·
IF 8.2
Quan Zhu,Yangyang Zhang,Xinyi Zhu,Huijuan Zhang,Chuyu Xiao,Yingying Yang,Ting Huang,Jun Lu,Chang Liu,Chunjing Chen,Yueyuan Zhou,Tao Liu,Biyuan Liu,Fangguo Lu
Ferroptosis and cuproptosis are promising anti-tumor treatment strategies. Elesclomol (ES) is a kind of common cuproptosis inducer, and cisplatin (DDP) is a commonly used drug in liver cancer chemotherapy, which can induce cells to undergo ferroptosis. Both of these cell death processes require inducing cells to generate oxidative stress. Therefore, elesclomol and cisplatin may have a synergistic effect in anti-tumor treatment. Here, we designed an active oxygen-responsive nano-delivery system and conducted in vitro and in vivo to study the synergistic anti-liver cancer effect of elesclomol and cisplatin. Our data showed that the elesclomol nanoparticles can effectively inhibit the growth of liver cancer cells and showed extremely low organ toxicity. Elesclomol exhibited a synergistic effect with cisplatin in vitro, but the combined treatment of the two did not outperform single drug treatment in vivo. The reason might be that the nuclear factor erythroid 2-related factor 2 (Nrf2) protein in liver cancer cells is feedback-expressed, inhibiting the oxidative stress effects induced by elesclomol and cisplatin. Therefore, this study provides reference data for exploring the mechanism of elesclomol’s synergistic anti-liver cancer treatment with cisplatin and offers a feasible strategy for future precise liver cancer treatment and improving chemotherapy efficacy.
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Jiaqi Li,Zheng Zhong,Yuhe Tan,Xiaohong Ma,Ruohong Wang,Guoyao Gao,Xian Zhang,Ziqing Zhou,Yin Zhao,Jia Liu,Xufang Sun
Background The multifaceted pathogenesis of diabetic retinopathy (DR) involves numerous pathways, among which oxidative stress and Rho-associated kinase (ROCK) signaling are critically implicated. The failure of current anti-VEGF monotherapies to address these key pathological processes limits their efficacy. While the ROCK inhibitor Fasudil is a promising candidate, its clinical translation for DR is hindered by poor ocular retention and lack of target specificity.Methods We engineered a reactive oxygen species (ROS)- and pH-dual responsive polydopamine nanoplatform (Fasudil@PDA) to deliver Fasudil while concurrently scavenging oxidative stressors.Results The Fasudil@PDA nanoparticles achieved a high drug loading capacity of ~28%. The release kinetics were specifically engineered to be responsive to the DR microenvironment. Under high ROS conditions in vitro, the platform demonstrated a sustained and efficient release profile, achieving a cumulative release of 87.3% over 56 days — demonstrating remarkable longevity. Separately, the pH-responsive drug release capability was also confirmed under acidic conditions. The platform effectively neutralized multiple ROS species in vitro and significantly restored endothelial barrier integrity by inhibiting the ROCK/MLC pathway. In a laser-induced choroidal neovascularization model, a single injection suppressed pathological angiogenesis by 45%. In diabetic mice, the same treatment markedly reduced vascular leakage, attenuated neuroinflammation, and restored retinal function, with b-wave amplitudes recovering to near-normal levels.Conclusion This study establishes a multi-faceted nanotherapeutic strategy that synergizes sustained, long-acting ROCK inhibition with innate antioxidant activity. Designed to be activated by the pathological cues of DR, including acidic pH and ROS, our approach precisely targets multiple pathological pathways, offering a promising and translatable paradigm for overcoming the limitations of current monotherapies.
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DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2026
·
IF 3.3
Xiaofeng Jia,Yijia Guan,Weijie Cao,Xiaoshuo Zhang,Huazhen Duan,Hui Guo,Huichang Chen,Binbin Wang,Tao Li,Jianguo Liao
Alzheimer’s disease (AD), marked by the misfolding/aggregation of β-amyloid (Aβ), is a major global health challenge. Polyoxometalates (POMs), as anionic therapeutic agents, exhibit potential in depolymerizing Aβ fibrils, inhibiting Aβ fibrillation, and photocatalyst. To achieve targeted reactive oxygen species (ROS) amplification, we developed a chitosan-modified near-infrared (NIR)-responsive upconversion nanoplatform, UCNPs(Tm/Er)@SiO2@GPS@CH, as a targeted carrier for POMs. The nanoplatform was constructed by sequentially modifying upconversion nanoparticles (UCNPs) with a silica layer, 3-glycidoxypropyltrimethoxysilane (GPS, as a linker), and chitosan (CH, a cationic biomacromolecule). The cationic CH layer enabled efficient loading of anionic POMs through electrostatic interactions with an optimal POMs loading capacity of 415.41 μg/mg that positively correlated with CH modification levels. Under NIR irradiation, the nanoplatform triggered a photodynamic effect with abundant ROS. Notably, compared with the control group and Aβ monomer group, the ROS generation in the Aβ fibril group was approximately doubled, which further enhanced the targeted therapeutic efficacy of system. By integrating NIR responsiveness, cationic chitosan, targeted ROS generation, and low systemic toxicity, the nanoplatform provides a novel strategy for the photooxidative treatment of AD and offers insights into the design of chitosan-modified upconversion nanoparticles-based drug carrier systems.
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PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Xuedi Zhang,Xue Zhao,Zheng Hua,Shanghua Xing,Jiaxuan Li,Siyuan Fei,Mingqian Tan
Smart delivery systems with stimuli-responsive capability are able to improve the bioaccessibility through increasing the solubility, physicochemical stability and biocompatibility of bioactive compounds. In this study, the astaxanthin nanoparticles with reactive oxygen species (ROS) and pH dual-response function were design and constructed using poly (propylene sulfide) covalently modified sodium alginate as carriers based on ultrasonic assisted self-assembly strategy. Atomic force microscope and scanning electron microscope analysis showed that the nanoparticles were spherical in shape with a size of around 260 nm. Meanwhile, the astaxanthin nanoparticles showed both pH and ROS stimuli-responsive release characteristics. In vitro cell experiments showed that astaxanthin nanoparticles significantly inhibited the production of ROS and mitochondrial depolarization induced by oxidative stress . In vivo colitis experiment of mice revealed that astaxanthin nanoparticles could significantly relieve colitis, protect the integrity of colon tissue and restore the expression of tight junction proteins ZO-1 and occludin . The abundance of Lactobacillus and Lachnospiraceae , and the ratio of Firmicutes/Bacteroidota of gut microbiota were significantly improved after intervention of the stimuli-responsive astaxanthin nanoparticles. This work provided a simple strategy for constructing ROS/pH dual response delivery system, which provided an experimental basis for improving the oral bioavailability of hydrophobic active compounds.
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Wanfeng Wu,Yanan Qin,Yan Fang,Yukun Zhang,Shuxuan Shao,Fanxing Meng,Minwei Zhang
Currently, graphene quantum dots (GQDs) are widely used as antibacterial agents, and their effects are dependent on the reactive oxygen species (ROS) generated by photodynamic and peroxidase activities. Nevertheless, the supply of substrates or light greatly limits GQDs application. Besides, due to compensatory mechanisms in bacteria, comprehensive analysis of the molecular mechanism underlying the effects of GQDs based on cellular-level experiments is insufficient. Therefore, N-GQDs with inherent excellent, broad-spectrum antibacterial efficacy under acidic conditions were successfully synthesized. Then, via multi-omics analyses, the antibacterial mechanisms of the N-GQDs were found to not only involve generation ROS but also be associated with changes in osmotic pressure , interference with nucleic acid synthesis and inhibition of energy metabolism. More surprisingly, the N-GQDs could destroy intracellular acid-base homeostasis , causing bacterial cell death. In conclusion, this study provides important insights into the antibacterial mechanism of GQDs, offering a basis for the engineering design of antibacterial nanomaterials .
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PubMed
高影响因子
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