Nanoscale
·
2021
·Vol. 13
·期 47
·20170-20185
·
IF 7.79
Yanqin Song,Muhammad Ismail,Qi Shan,Jianing Zhao,Yanping Zhu,Leiming Zhang,Yuan Du,Longbing Ling
Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder that has seriously affected human health worldwide and its current management requires more successful therapeutic approaches. The combination of nanomedicines and pathophysiology into one system may provide an alternative strategy for precise RA treatment. In this work, a practical ROS-mediated liposome, abbreviated as Dex@FA-ROS-Lips that comprised synthetic dimeric thioether lipids (di-S-PC) and a surface functionalized with folic acid (FA), was proposed for dexamethasone (Dex) delivery. Incorporation with thioether lipids and a FA segment significantly improved the triggered release and improved the triggered release of cytotoxic Dex as well as the active targeting of RA, altering its overall pharmacokinetics and safety profiles in vivo. As proof, the designed Dex@FA-ROS-Lips demonstrated effective internalization by LPS-activated Raw264.7 macrophages with FA receptor overexpression and released Dex at the inflammatory site due to the ROS-triggered disassembly. Intravenous injection of this Dex@FA-ROS-Lips into adjuvant-induced arthritis (AIA) mice led to its incremental accumulation in inflamed joint tissues and significantly alleviated the cartilage destruction and joint swelling via suppression of proinflammatory cytokines (iRhom2, TNF-α and BAFF), as compared to the effect of commercial free Dex. Importantly, the Dex@FA-ROS-Lips nanoformulation showed better hemocompatibility with less adverse effects on the body weight and immune organ index of AIA mice. The anti-inflammatory mechanism of Dex@FA-ROS-Lips was further studied and it was found that it is possibly associated with the down-regulation of iRhom2 and the activation of the TNF-α/BAFF signaling pathway. Therefore, the integration of nanomedicines and the RA microenvironment using multifunctional Dex@FA-ROS-Lips shall be a novel RA treatment modality with full clinical potential, and based on the enhanced therapeutic effect, the signaling pathway of iRhom2/TNF-α/BAFF reasonably explained the mechanism of Dex@FA-ROS-Lips in anti-RA, which suggested a molecular target for RA therapy and other inflammatory diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Animal Science and Biotechnology
·
2023
·Vol. 14
·期 1
·1-17
·
IF 7
He Zhaoqi,Zhao Caijun,He Yuhong,Liu Zhuoyu,Fan Guyue,Zhu Kun,Wang Yiqi,Zhang Naisheng,Fu Yunhe,Hu Xiaoyu
Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusion sIn conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Yuanming Xing,Fujia Kang,Chuanxin Chen,Jingjing Lan,Cuiyu You,Kai Dong,Ying Zhang
Oxidative stress is a key factor in the progression of inflammatory bowel disease (IBD) and enteropathic arthritis, and scavenging excessive intracellular reactive oxygen species (ROS) is an effective therapeutic strategy. Chondroitin sulfate-modified cerium oxide nanozymes (CS-CNPs) were synthesized for the first time in this study with dual-cell targeting properties, which regulated the redox homeostasis of the inflammatory sites of the colon and joints through scavenging intracellular ROS, and thus treating IBD and enteropathic arthritis. The results showed that CS-CNPs possessed multiple mimetic antioxidant enzyme activities and could target inflammatory intestinal epithelial cells and macrophages to scavenge ROS. The good cellular targeting of CS-CNPs enhanced the ability to scavenge ROS from inflammatory cells in the colon of colitis mice, and they produced a good IBD therapeutic effect by inhibiting the intestinal inflammatory response and repairing the damaged intestinal mucosal barrier. In addition, for the treatment of experimental enteropathic arthritis, CS-CNPs demonstrated colonic and joint inflammatory site targeting, and exerted anti-inflammatory effects by scavenging ROS. The conveniently synthesized dual-targeted nanozymes lay the foundation for “kill two birds with one stone” in treating IBD and enteropathic arthritis, as well as an effective solution for the multi-targeted treatment of oxidative stress-related diseases. Download: Download high-res image (125KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Jia Ding,Nan Wang,Xiao-kun Ouyang,Junhong Ling
Ulcerative colitis (UC) is associated with epithelial barrier disruption, oxidative stress, inflammation, and gut microbiota dysbiosis. Oral colon-localized delivery remains challenging because therapeutic cargos must resist gastric exposure, avoid premature release, be retained at inflamed colonic sites, and respond to pathological microenvironments. Herein, a pH/reactive oxygen species (ROS) dual-responsive calcium alginate microalgal hydrogel, denoted SP@GaTa@ALG (SGA), was developed for localized UC therapy. Gallium-tannic acid nanoparticles (GaTa NPs) were loaded onto Spirulina (SP) and encapsulated within a Ca 2+ -crosslinked alginate matrix. The calcium alginate network provided gastric protection and pH-dependent control over Ga 3+ diffusion, while GaTa enabled ROS-responsive Ga 3+ release and antioxidant activity. In vitro , SGA scavenged free radicals, reduced intracellular ROS accumulation, protected epithelial cells against H 2 O 2 -induced injury, preserved mitochondrial membrane potential, and promoted an anti-inflammatory-like macrophage phenotype. After oral administration, SGA showed prolonged gastrointestinal retention and enhanced colonic localization compared with non-encapsulated SP@GaTa (SG). In dextran sulfate sodium (DSS)-induced colitis mice, SGA alleviated body-weight loss, reduced disease activity, restored colon length, improved zonula occludens-1 (ZO-1) and Occludin expression, suppressed inflammatory mediators, and was associated with gut microbiota remodeling. These findings support SGA as a traceable, carbohydrate-polymer-based oral platform for inflammation-responsive UC intervention.
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Chengfang Zhang,Dong Wang,Qinglong Liu,Jingchun Tang
Nanoscale zero-valent iron (nZVI) can react with molecular oxygen to produce reactive oxygen species, but very low yield limits its widespread use. In this study, the effect of ligand-citric acid (CA) addition on the dissolved oxygen (DO) activation for in-situ generation of ROS and subsequent 2,4-DCP degradation by graphene carbon layer coated nZVI composites (GBC@nZVI) was systematically investigated. It was found that the introduction of CA significantly increased the ROS production and resulted in the generation of OH, O 2 − and 1 O 2 with values of 2.1, 2.3, and 1.5 times higher than that in systems without CA, respectively. Ligand CA could enhance the degradation of adsorbed 2,4-DCP over a wide pH range. The CA addition resulted in a significant increase in the degradation of 2,4-DCP from 40.8 % to 79.9 % and a significant decrease in the adsorption from 51.1 % to 19.1 % compared to the system without CA. This phenomenon can be attributed to the fact that the incorporation of CA promoted the efficient recycling of Fe(II)/Fe(III) in the surface-bound state from the iron oxide film on the GBC@nZVI which enhanced the generation of interfacial ROS using DO, and further facilitated the degradation of adsorbed 2,4-DCP rather than immobilization by adsorption alone. On the other hand, the formation of Fe(Ⅲ)-CA complexes with high stability provides enough soluble Fe(II) to produce more ROS in solution via the oxygen reduction. Furthermore, the graphene carbon layer is able to act as an electron conductor to promote the efficient transfer of electrons except to inhibiting the rapid oxidation of Fe 0 . The study not only reveals the promotion effect of ligand-CA addition on the in-situ generation of ROS from nZVI activated dissolved oxygen, but also provides a simple and green strategy for the removal of electron-rich aromatic pollutants from water pollution.
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Hailing Wang,Liucan Wang,Yuhua Chen,Jixi Huang,Yuxin Xing,Lu Wang,Jixi Zhang,Hua Yang
Ceria nanozyme-based ROS scavengers hold a great potential in the treatment of inflammatory bowel disease (IBD) by microenvironment regulation. However, the currently developed nanotherapeutics suffer from difficulties in concomitantly achieving small sizes and stable interparticle dispersion which are pivotal to sufficient oxygen vacancies facilitating electron transfer and oxygen storage in the dynamic cycling of Ce3+/Ce4+ redox pairs. Herein, a hybrid nanosystem consisting of ceria nanodots supported on redox-active mesoporous hosts was developed to address the challenge of ROS scavenging, in particular the efficient downregulation of the readily renewable, highly concentrated H2O2 species. Specifically, Ce4+ ions oxidized from Ce3+ in weakly basic solution was captured and reduced in time by the abundant catechols on the mesoporous polydopamine nanoparticles. This led to strong restriction of ceria growth (~2.8 nm) in the ion precipitation process and efficient maintenance of Ce3+/Ce4+ ratio at a high value of 1.59 which is 4.8 fold higher than homogeneously nucleated ceria nanoparticles. By this design, the nanohybrid showed an attractive catalytic performance in scavenging multiple ROS species, particularly the fast and recyclable conversion of H2O2. Thereby, a significant suppression of the inflammatory cytokines/chemokines secretion was achieved by inhibiting the activation of NF-κB signaling pathways (5.1 fold higher as compared with the pristine ceria nanoparticles), downregulating the Nrf2 signaling pathway, and reducing the proportion of M1 macrophages at IBD sites. The therapeutic efficiency was also demonstrated by the effective repair of intestinal mucosal barrier by recovering the tight junction integrity in vivo. This study shed the light on the employment of redox-active hosts to support ceria catalysts for advancing anti-inflammation applications by boosting ROS scavenging performance.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Junjun Li,Rong Du,Qiong Bian,Danping Zhang,Siqian Gao,Anran Yuan,Xiaoying Ying,Youqing Shen,Jianqing Gao
During the occurring of cutaneous trauma, increasing oxidative stress response in wound site retards the progress of proliferation phase, impeding sequent efficient wound repair. At the same time, high-quality healing also requires adequate new blood vessels in order to furnish the wound site with a nutrient and oxygen-sufficient environment. Here we synthesized a novel hyaluronic acid (HA) material modified with a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (ATEMPO) for prevention of excessive reactive oxygen species (ROS) and promotion of angiogenesis after full-thickness skin excision in rats. Amines in ATEMPO attaching with carbonyls in HA chains was fabricated through N-acylation. The HA-g-TEMPO exerted a ROS-scavenging and angiogenesis-promoting function in vitro . In acute wound rat model, the wound closure efficacy was significantly improved to almost 55% at day 6 in comparison to 49% of HA, and wound sites in initial wound phase was also narrowed down sharply. Moreover, initially formed blood vessels were found in wound sites, further proved the angiogenesis-promoting function of HA-g-TEMPO. More interestingly, wound sites demonstrated an exciting regenerative healing effect which was characterized by marked skin appendages as well as reduced scarring. Therefore, this strategy showed a promising future that could be considered as a reliable and effective method to cutaneous wound healing.
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Yumeng Miao,Yun Zheng,Yanzhi Geng,Ling Yang,Na Cao,Yue Dai,Zhifeng Wei
Background: Peroxisome proliferator-activated receptor gamma (PPARγ) has the ability to counter Th17 responses, but the full mechanisms remain elusive. Herein, we aimed to elucidate this process in view of cellular metabolism, especially glutaminolysis. Methods: MTT, CCK-8, Annexin V-FITC/PI staining or trypan blue exclusion assays were used to analyze cytotoxicity. Flow cytometry and Q-PCR assays were applied to determine Th17 responses. The detection of metabolite levels using commercial kits and rate-limiting enzyme expression using western blotting assays was performed to illustrate the metabolic activity. ChIP assays were used to examine H3K4me3 modifications. Mouse models of dextran sulfate sodium (DSS)-induced colitis and house dust mite (HDM)/lipopolysaccharide (LPS)-induced asthma were established to confirm the mechanisms studied in vitro . Results: The PPARγ agonists rosiglitazone and pioglitazone blocked glutaminolysis but not glycolysis under Th17-skewing conditions, as indicated by the detection of intracellular lactate and α-KG and the fluorescence ratios of BCECF-AM. The PPARγ agonists prevented the utilization of glutamine and thus directly limited Th17 responses even when Foxp3 was deficient. The mechanisms were ascribed to restricted conversion of glutamine to glutamate by reducing the expression of the rate-limiting enzyme GLS1, which was confirmed by GLS1 overexpression. Replenishment of α-KG and 2-HG but not succinate weakened the effects of PPARγ agonists, and α-KG-promoted Th17 responses were dampened by siIDH1/2. Inhibition of KDM5 but not KDM4/6 restrained the inhibitory effect of PPARγ agonists on IL-17A expression, and the H3K4me3 level in the promoter and CNS2 region of the il-17 gene locus down-regulated by PPARγ agonists was rescued by 2-HG and GLS1 overexpression. However, the limitation of PPARγ agonists on the mRNA expression of RORγt was unable to be stopped by 2-HG but was attributed to GSH/ROS signals subsequent to GLS1. The exact role of PPARγ was proved by GW9662 or PPARγ knockout, and the mechanisms for PPARγ-inhibited Th17 responses were further confirmed by GLS1 overexpression in vivo . Conclusion: PPARγ agonists repressed Th17 responses by counteracting GLS1-mediated glutaminolysis/2-HG/H3K4me3 and GSH/ROS signals, which is beneficial for Th17 cell-related immune dysregulation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 9
·5044-5054
·
IF 3.361
Botao Qu,Yahong Han,Juan Li,Qian Wang,Bingyu Zhao,Xiaoyang Peng,Ruiping Zhang
Photoacoustic (PA) imaging has emerged as a promising bio-imaging technique due to its non-invasive visualization of lesions at great penetration depths. Fluorescence (FL) imaging in the second near-infrared window (NIR-II, 1000–1700 nm) achieves a higher imaging resolution and lower background signals compared to NIR-I. However, the single imaging method possesses its own disadvantages. Thus, we have demonstrated ZIF-8–IR820–MnPc–HA nanoparticles (ZIMH NPs) that can achieve visualization and localization of tumors in mice models with the help of a dual-modality PA/NIR-II FL imaging performance. Meanwhile, these excellent nanoparticles also induce the efficient generation of singlet oxygen (1O2) upon 808 nm laser illumination, and display excellent photodynamic therapy efficacy in cells, further indicating their potential application for in vivo PDT. In ZIMH NPs, hyaluronic acid (HA) impressively acts as a “sponge”, enhancing the generation of 1O2 and facilitating the cellular therapeutic effects. We believe that ZIF-8–IR820–MnPc–HA NPs present a brand-new strategy for the exploration of efficient PDT photosensitizers with dual-modality imaging performance for use in various biomedical applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xiaoya Hou,Hua Lin,Xiudi Zhou,Ziting Cheng,Yi Li,Xue Liu,Feng Zhao,Yanping Zhu,Peng Zhang,Daquan Chen
Although the clinical usage of drugs administration was raising, the application of nanoparticles encapsulating the hydrophobic drugs with plummy efficiency was very scarce for atherosclerosis (AS) treatment. In this work, a novel dual ROS-sensitive and CD44 receptors targeting amphiphilic carrier material, oligomeric hyaluronic acid-2′-[propane-2,2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (oHA-TKL-Fc), named HASF, was synthesized and characterized by 1 H-NMR spectra. Then, we combined curcumin (Cur) with HASF into nano-micelles ( [email protected] micelles) by self-assembling method. The resulting [email protected] micelles had the average size of 150.8 nm and zeta potential of -35.04 mV to maintain the will-defined spheroidal structure and stability. Importantly, the [email protected] micelles had ultrahigh entrapment efficiency (about 51.41 %). Moreover, in vitro release study, Cur release from [email protected] micelles was effective in the reactive oxygen species (ROS) condition, and the release rate was interrelated with the concentration of hydrogen peroxide (H 2 O 2 ). Further, fluorescence imaging showed that the [email protected] micelles could more selective access to Raw 264.7 cells than free Cur via oHA-receptor mediated endocytosis. The MTT assay attested the safety of amphiphilic carrier material HASF. Additionally, the results of in vivo Oil red O lipid staining studies showed that the lesion area of the aorta was reduced to 47.3±3.4 % with [email protected] micelles, compared with the lesion area of Cur group (63.2±2.7 %), [email protected] micelles had the more remarkable effect in reducing lesion area (*P < 0.05). Consequently, the novel dual ROS-sensitive and CD44 receptors targeting drug delivery system would become a promising strategy for atherosclerosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Zhang Yuan,Bailong Tao,Ye He,Ju Liu,Chuanchuan Lin,Xinkun Shen,Yao Ding,Yonglin Yu,Caiyun Mu,Peng Liu,Kaiyong Cai
To inhibit bacterial infection in situ and improve osseointegration are essentially important for long-term survival of an orthopedic implant , in particular for infection-associating revision surgery. Herein, we fabricate a functional molybdenum disulfide (MoS 2 )/polydopamine (PDA)-arginine-glycine-aspartic acid (RGD) coating on titanium (Ti) implant to address above concerns simultaneously. The coating not only improved the osteogenesis of mesenchymal stem cells (MSCs), but also endowed Ti substrates with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. It accelerated glutathione (GSH) oxidation via photothermal energy and induced intrinsic ROS-independent oxidative stress damage deriving from MoS 2 nanosheets . The results displayed that RGD-decorated MoS 2 nanosheets significantly increased the cellular osteogenic behaviors of MSCs via up-regulating osteogenesis-related genes (ALP, Runx2, Col I and OCN) in vitro. Moreover, the functionalized Ti substrates demonstrated great antibacterial efficiency of over 92.6% inhibition for S. aureus and E. coli under NIR-irradiation. Hyperthermia induced by photothermal effect accelerated the GSH consumption and ROS-independent oxidative stress destroyed the integrity of bacteria membranes , which synergistically led to protein leakage and ATP decrease. Furthermore, co-culture experiment showed that S. aureus contamination was efficiently cleaned from MoS 2 /PDA-RGD surface after NIR photothermal treatment, while MSCs adhered and proliferated on the MoS 2 /PDA-RGD surface. In an S. aureus infection model in vivo, MoS 2 /PDA-RGD modified Ti rods killed bacteria with an efficiency of 94.6% under NIR irradiation, without causing damage to normal tissue. More importantly, the MoS 2 /PDA-RGD modified Ti implants accelerated new bone formation in comparison with TNT implants in vivo .
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2019
·
IF 3.585
Wu Luo,Yiyi Jin,Gaojun Wu,Weiwei Zhu,Yuanyuan Qian,Yali Zhang,Jieli Li,Aisong Zhu,Guang Liang
Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. A multitude of factors are involved in the pathogenesis of DCM including chronic inflammation and oxidative stress . We have recently shown that compound LF10 prevents inflammatory responses in an animal model of lung injury. In the present study, we explored the protective effects and mechanism of LF10 against DCM using a mouse model of streptozotocin-induced diabetes and high glucose (HG)-challenged cultured cardiomyocytes. We show that LF10 suppressed diabetes-induced cardiomyocyte hypertrophy and fibrosis , which was accompanied by preservation of cardiac function in mice. Mechanistically, LF10 prevented increases in the levels of pro-inflammatory molecules and oxidative stress under in vitro and in vivo diabetic conditions. Moreover, LF10 restored HG-downregulated sirtuin 1 (SIRT1) in cardiomyocytes and prevented HG-induced activation of MAPKs. Using specific small-molecule regulators, we found that SIRT1 was an upstream signal of MAPKs. In conclusion, LF10 inhibited ROS and MAPKs-mediated inflammation by restoring SIRT1, and prevented development of DCM. LF10 targeted both oxidative stress and inflammation, two tightly interconnected pathogenic pathways, which makes LF10 a highly advantageous therapeutic drug potential.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）