Advanced Science
·
2025
·
IF 14.1
Haoran Lv,Guanning Huang,Hongyu Li,Hanzhi Liang,Huajing Peng,Kefei Wu,Wenfang Chen,Dandan Zhang,Kexin Ma,Yufei Du,Siweier Luo,Yi Zhou,Haiping Mao,Wei Chen,Tianfeng Chen,Yiming Zhou,Qinghua Liu
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is largely driven by dysregulated macrophage responses. However, the heterogeneity of macrophages hinders the development of targeted therapies for LN. Here, through single-cell analysis and clinical specimen validation, it is found that pro-inflammatory M2b macrophages are increased in the kidneys of patients with LN and are strongly associated with clinical indicators. To target and modulate M2b macrophages, mannose-functionalized selenium nanoparticles are engineered that can selectively suppress M2b polarization and activation by reducing reactive oxygen species (ROS), restoring mitochondrial function, and inducing selenoprotein glutathione peroxidase 1 (GPX1). In vivo, SeZM NPs accumulate in the kidneys of lupus mice and reduce M2b-derived pro-inflammatory cytokines, preserving renal structure and function. Together, these findings highlight pro-inflammatory M2b macrophages as pathogenic drivers of LN and demonstrate the translational potential of selenium-based nanotherapy.
研究领域:
免疫学
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纳米医学
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自身免疫性疾病
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肾脏病理学
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氧化还原生物学
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2022
·
IF 3.889
Bo Lu,Jianhua Li,MingTai Gui,Lei Yao,Mingsong Fan,Xunjie Zhou,Deyu Fu
Context Salvianolic acid B (SalB) can attenuate myocardial ischemia/reperfusion (I/R) injury, but the mechanisms are not entirely known.Objective Our study investigates if SalB protects cardiomyocytes against I/R injury by regulating Tripartite motif (TRIM) protein.Materials and methods AC16 cardiomyocytes were treated with I/R, and then with SalB (10, 25 and 50 μM) for 24 h, while control cells were cultured under normal conditions. Female Sprague-Dawley rats were subjected to I/R injury, and then intravenously injected with 20, 40, or 60 mg/kg SalB or saline, as a control, rats received sham operation and saline injection.Results Upon treatment, apoptotic rate, reactive oxygen species (ROS), and malondialdehyde (MDA) were increased 10-, 3.8-, and 1.3-fold, respectively, while superoxide dismutase (SOD) activity was reduced by 62.1% compared to control cells. I/R treatment elevated the mRNA and protein expression of TRIM8. SalB treatment remarkably abolished the above-mentioned effects of I/R treatment. TRIM8 knock-down could partially alleviate I/R-induced myocardial injury. TRIM8 overexpression promoted cardiomyocyte injury, which was alleviated by SalB. Moreover, TRIM8 negatively regulated protein expression of antioxidant enzyme glutathione peroxidase 1 (GPX1). TRIM8 protein interacted with GPX1 and TRIM8 overexpression promoted GPX1 ubiquitnation. GPX1 knock-down abolished the protective effects of SalB on I/R-injured cardiomyocytes. Our in vivo experiments confirmed the effects of SalB on I/R-induced myocardial injury.Discussion and conclusions SalB protected cardiomyocytes from I/R-induced apoptosis and oxidative stress in vitro and in vivo, which was partly mediated by the TRIM8/GPX1 axis. This suggests that down-regulation of TRIM8 expression may ameliorate I/R-induced myocardial injury.
研究领域:
心脏病学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 13.2
Zhen Wan,Qian Wu,Tian Deng
Periodontitis is a chronic inflammatory disease initiated by bacterial pathogens, resulting from complex interactions between microbial infection and host immune responses. In current clinical practice, antibiotics represent the most frequently utilized adjunctive therapy for periodontitis. However, the overuse of antibiotics not only contributes to the emergence of bacterial resistance but also demonstrates limited efficacy in inflammation resolution. In this study, we synthesized selenium/Ti 3 C 2 (Se/Ti 3 C 2 ) through a one-step redox method using Ti 3 C 2 as a template. The Se/Ti 3 C 2 demonstrated significant antibacterial activity against Escherichia coli ( E.coli ), Staphylococcus aureus ( S.aureus ), and Porphyromonas gingivalis ( P.gingivalis ) under near-infrared (NIR) light irradiation, as evidenced by comprehensive evaluations including colony-forming unit (CFU) counting assays, live-dead fluorescence staining, scanning electronic microscopy (SEM) observations, growth curves, and membrane potential staining assays. Furthermore, the anti-inflammatory and antioxidant properties of Se/Ti 3 C 2 were investigated using various methodologies, including 1,1-diphenyl-2-pyridine-hydratedacyl (DPPH) scavenging assay, 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) scavenging assay, glutathione peroxidase (GPX) activity measurement, intracellular reactive oxygen species (ROS) fluorescence staining, flow cytometry, and quantitative real-time polymerase chain reaction (qPCR) assays. Through GPX1 gene knockdown experiments, we demonstrated that the anti-inflammatory effects of Se/Ti 3 C 2 were closely associated with GPX1 expression. RNA sequencing analysis was subsequently performed to elucidate the underlying mechanisms of its anti-inflammatory and antioxidant activities. Finally, in vivo experiments using a mouse periodontitis model demonstrated the remarkable therapeutic potential of Se/Ti 3 C 2 in periodontitis treatment. Therefore, Se/Ti 3 C 2 holds great promise as a potential alternative to antibiotics, emerging as a novel therapeutic material for periodontitis treatment.
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Binhua Zou,Zushuang Xiong,Yanzi Yu,Sujiang Shi,Xiaoling Li,Tianfeng Chen
Osteoclast hyperactivation stands as a significant pathological factor contributing to the emergence of bone disorders driven by heightened oxidative stress levels. The modulation of the redox balance to scavenge reactive oxygen species emerges as a viable approach to addressing this concern. Selenoproteins, characterized by selenocysteine (SeCys 2 ) as the active center, are crucial for selenium-based antioxidative stress therapy for inflammatory diseases. This study reveals that surface-active elemental selenium (Se) nanoparticles, particularly lentinan-Se (LNT-Se), exhibit enhanced cellular accumulation and accelerated metabolism to SeCys 2 , the primary active Se form in biological systems. Consequently, LNT-Se demonstrates significant inhibition of osteoclastogenesis. Furthermore, in vivo studies underscore the superior therapeutic efficacy of LNT-Se over SeCys 2 , potentially attributable to the enhanced stability and safety profile of LNT-Se. Specifically, LNT-Se effectively modulates the expression of the selenoprotein GPx1, thereby exerting regulatory control over osteoclastogenesis inhibition, and the prevention of osteolysis. In summary, these results suggest that the prompt activation of selenoproteins by Se nanoparticles serves to suppress osteoclastogenesis and pathological bone loss by upregulating GPx1. Moreover, the utilization of bioactive Se species presents a promising avenue for effectively managing bone disorders.
研究领域:
生物材料
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生物医学工程
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药理学
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骨骼生物学
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DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Jingyuan Wang,Zekun Wang,Yuqing Li,Yajun Hou,Chenyang Yin,Endong Yang,Ziyu Liao,Cundong Fan,Lisandra L. Martin,Dongdong Sun
Alzheimer's disease (AD) as a common neurodegenerative disease showed progressive cognitive dysfunction and behavioral impairment. Currently, the deposition of amyloid β-protein (Aβ) remains the main pathomechanism. However, preventing neuronal death induced by Aβ remains elusive, and no effective strategy in clinic was found to combat AD. Herein, a multifunctional double selenium nanosphere (CLNDSe) was designed and prepared, and A 2A AR agonist (CGS) modification endowed CLNDSe NPs with A 2A AR-targeted blood brain barrier (BBB) delivery in vitro and in vivo . CLNDSe NPs after modification of LPFFD short peptide effectively inhibited Aβ 42 aggregation and attenuated Aβ 42 -induced neural toxicity by inhibiting oxidative damage and mitochondrial dysfunctions. Nerve growth factor (NGF) linked to large Se sphere significantly attenuated Tau phosphorylation and gliocytes activation in APP/PS1 mice. CLNDSe NPs administration in vivo also effectively restored GPX1/4 antioxidant ability, alleviated neural loss and neurofibrillary tangles, prevented neural ferroptosis, and eventually ameliorated cognitive deficits of APP/PS1 mice. Importantly, CLNDSe NPs showed good safety and biocompatibility. Taken together, our finding validated the rational design that BBB-targeted delivery of double selenium nanosphere may be a novel strategy to ameliorate Alzheimer's disease by inhibiting neural ferroptosis.
研究领域:
神经科学
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纳米技术
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药理学
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神经退行性疾病
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DOI
高影响因子
iMeta
·
2025
·Vol. 4
·期 6
·e70100
·
IF 33.2
Sen-Lin Zhu,Yu-Nan Yan,Ming-Hui Jia,Hou-Cheng Li,Bo Han,Tao Shi,Lian-Bin Xu,Xiao-Wen Wang,Qi Zhang,Wei-Jie Zheng,Jing-Hong Xu,Liang Chen,Wenlingli Qi,Sheng-Jun Cai,Xin-Peng Chen,Feng-Fei Gu,Jian-Xin Liu,George E. Liu,Yu Jiang,Dong-Xiao Sun,Ling-Zhao Fang,Hui-Zeng Sun
Oxygen signaling is essential for cellular homeostasis and tightly linked to metabolism, growth, and survival. In dairy cows, oxidative stress, arising from an imbalance between reactive oxygen species and antioxidants, is a major postpartum challenge that contributes to disease susceptibility. Using single-cell transcriptomes from 1,793,854 cells across 59 tissues, we analyzed oxygen signaling states within 1006 cellular clusters. The gastrointestinal tract (GIT) epithelium, particularly the forestomach, exhibits the strongest antioxidant activity, closely coupled to oxidative phosphorylation (OXPHOS) and glycolysis, with OXPHOS levels surpassing those of cardiomyocytes and hepatocytes (Cohen's d > 3.9, p < 0.001). Pseudotime and spatial transcriptomics demonstrated that both OXPHOS and antioxidant capacity increase progressively along the basal-to-luminal differentiation axis. Functional experiments in primary rumen epithelial cells showed that antioxidant supplementation or GPX1 modulation enhances mitochondrial respiration, boosts intracellular glutathione, and accelerates epithelial differentiation. Limited proteolysis-mass spectrometry (LiP-MS) analysis identified GPX1 , GSTP1 , COX7A2 , and COX6B1 as candidate targets mediating antioxidant-driven metabolic remodeling. Together, these results reveal a redox-governed metabolic program in the forestomach epithelium and highlight antioxidant interventions as a potential strategy to support epithelial development and mitigate oxidative stress-related disorders in dairy cattle. Graphical Single-cell and transcriptomics from 1.79 million cells identify the forestomach epithelium as the dominant site of antioxidant activity and oxidative phosphorylation (OXPHOS) in the bovine gastrointestinal tract. Along the basal-to-luminal differentiation axis, antioxidant capacity and OXPHOS rise in a coordinated metabolic–redox gradient. Primary rumen cell assays show that this gradient is strengthened by Cys-Cys-Cys supplementation or modulation of GPX1 expression, demonstrating a direct causal influence on epithelial metabolism. Key redox-metabolic regulators, including GPX1 and GSTP1 , mediate these responses. Overall, antioxidants actively drive metabolic remodeling and promote epithelial differentiation in the cattle forestomach epithelium. Highlights A single-cell transcriptomic atlas of 1.79 million bovine cells revealed the forestomach epithelium as one of the most antioxidant-active tissues. As the forestomach epithelium differentiates from the basal layer towards the luminal surface, both mitochondrial respiration and antioxidant capacity progressively intensify, establishing a coupled metabolic–redox gradient. Functional assays identified GPX1 as a key antioxidant target mediating OXPHOS and cell differentiation.
研究领域:
动物科学
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反刍动物生理学
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转录组学
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氧化还原生物学
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代谢
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单细胞分析
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Fan Yang,Rui Shu,Wenyu Dai,Bin Li,Chuang Liu,Hang Yang,Hannah M. Johnson,Sheng Yu,Ding Bai,Weizhong Yang,Yi Deng
Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H 2 Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe 2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H 2 Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H 2 Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H 2 Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.
研究领域:
生物材料
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伤口愈合
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生物医学工程
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细胞生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xudong Yao,Miner Hu,Xinrang Zhai,Junxin Lin,Xiaojun Xia,Wei Wei,Shudong Xia
Elderly patients predispose to cardiovascular implantable electronic devices (CIEDs) pocket infections due to multiple comorbidities. Treating infections with the antibiotics further carry higher risks for complications, and surgical intervention can be costly when device removal and reimplantation are required, both emphasizing the importance of novel preventive strategies to minimize the incidence of pocket infections. To meet the unique needs for elderly, we constructed an CIED surface modified hydrogel which crosslinked polyethylene glycol diacrylate (PEGDA) with hyaluronic acid-nitrobenzene (HN) to form the polymeric structures that mimic the natural environment for promoting “Pocket” surrounding tissue integration and healing. Importantly, we synthesized the new peptidomimetics FK-13 derived by shortening amino acid sequence of LL-37 which is the only human cathelicidin-derived antimicrobial peptide. By incorporating FK-13 with initial PN hydrogel via Schiff base formation, the created PN-FK hydrogel exhibited broad-spectrum antimicrobial activity against bacteria with excellent biocompatibility and mechanical properties in a long-term release manner. In an in vitro setting, PN-FK hydrogel demonstrated the regeneration capacity by expression of Hmox1, Col5 and Col6 associated genes in fibroblasts as well as expression of Gpx1, Cdc20 and MMP9 genes in stem cells to accelerate self-renewal, collagen secretion and reconstitution of matrix components. In the following in vivo model of subcutaneous implantation, CIED-shape titanium mesh with surface modification by PN-FK hydrogel efficiently subsided over-inflammation compared to bare titanium implant, and expedited collagen deposition and angiogenesis in peri -pocket tissues within 2 weeks. These findings underscore the potential of the PN-FK hydrogel as a transformative approach to CIED postoperative management, offering a dual-action solution that combines infection resistance with tissue regeneration capabilities.
研究领域:
生物医学工程
·
材料科学
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生物材料
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组织工程
·
抗菌技术
·
心脏病学
·
老年医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）