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PLoS One · 2016 ·Vol. 11 ·期 2 ·e0149032 · IF 3.057

Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways

Zhao Gao,Yu Han,Yunhui Hu,Xiaoyan Wu,Yongbin Wang,Xiaoqun Zhang,Jinjuan Fu,Xue Zou,Jun Zhang,Xiongwen Chen,Pedro A. Jose,Xi Lu,Chunyu Zeng

Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1β), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1β. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation.

研究领域: 药理学 · 肾病学 · 氧化应激与炎症
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JOURNAL OF PERIODONTAL RESEARCH · 2023 · IF 3.5

Resveratrol modulates the inflammatory response in hPDLSCs via the NRF2/HO-1 and NF-κB pathways and promotes osteogenic differentiation

Yifan Ma,Yi Qian,Yuteng Chen,Xiaoxu Ruan,Xiaoya Peng,Yi Sun,Jue Zhang,Jingjing Luo,Songlin Zhou,Chao Deng

Objective The purpose of this study was to investigate resveratrol's specific role as an anti-inflammatory and osteogenic differentiation of hPDLSCs in periodontitis and to reveal the mechanisms involved. Background Numerous studies have shown that inhibiting the inflammatory response of periodontal tissues and promoting the regeneration of alveolar bone are crucial treatments for periodontitis. Resveratrol has been found to have certain anti-inflammatory property. However, the anti-inflammatory mechanism and osteogenic effect of resveratrol in periodontitis are poorly understood. Materials and Methods We constructed an in vitro periodontitis model by LPS stimulation of hPDLSCs and performed WB, RT-qPCR, and immunofluorescence to analyze inflammatory factors and related pathways. In addition, we explored the osteogenic ability of resveratrol in in vitro models. Results In vitro, resveratrol ameliorated the inflammatory response associated with activation of the NF-κB pathway through activation of the NRF2/HO-1 pathway, characterized by inhibition of p65/p50 nuclear translocation and the proinflammatory cytokines interleukin-1β levels. Resveratrol also has a positive effect on osteogenic differentiation. Conclusions Observations suggest that resveratrol modulates the inflammatory response in hPDLSCs via the NRF2/HO-1 and NF-κB pathways and promotes osteogenic differentiation.

CAS / MDL: 501-36-0
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CRYSTENGCOMM · 2023 ·Vol. 25 ·期 38 ·5452-5460 · IF 3.1

Upconversion luminescence and temperature sensing properties of Yb2(MoO4)3:Ln3+ (Ln = Ho, Tm, Er) phosphors based on energy transfer

Huimin Du,Yunhao Liang,Xingzuo Liu,Yue Deng,Jie Yang,Jun Yang,Shanshan Hu

Yb2(MoO4)3:Ln3+ (Ln = Ho, Tm, Er) phosphors were synthesized by a hydrothermal method with further calcination. The crystal structure and morphology of the samples were characterized by X-ray diffraction and scanning electron microscopy. The effects of rare earth ion interaction in the Yb2(MoO4)3:Ln3+ phosphors on the upconversion (UC) luminescence properties and energy transfer process at different doping concentrations were discussed. It is concluded that by doping Ho3+, Tm3+, and Er3+ in the Yb2(MoO4)3 host, the phosphors emit orange-yellow, blue and green light, respectively, and the energy transfer from Yb3+ → Ho3+/Er3+ and Yb3+ → Tm3+ is a two and three photon process, respectively. Under the excitation of a 980 nm laser, by changing the Ho3+/Tm3+ ratio in doped Yb2(MoO4)3, we have realized the transition of phosphors from cold white light to warm white light. The temperature sensitivity of the 2H11/2 and 4S3/2 energy levels of Yb2(MoO4)3:Er3+ in the range of 323–573 K was studied by the FIR technology. The experimental results show that the maximum absolute sensitivity was 0.0081 K−1 at 573 K and the maximum relative sensitivity was 0.01 K−1 at 323 K. Compared with other materials, the Er3+ doped Yb2(MoO4)3 phosphor is an excellent optical temperature sensing material.

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Pharmaceuticals · 2022 ·Vol. 15 ·期 12 ·1548 · IF 5.215

Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways

Fei Yang,Cuizhen Shen

On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway

CAS / MDL: 67920-52-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INORGANIC CHEMISTRY · 2022 · IF 5.436

RE(OH)2NO3 (RE = Tb, Dy, Ho, and Er): Synthesis and Nonlinear Optical Properties of Water-Resistant Lanthanide Hydroxide Nitrates

Min Chen,Zhengli Liang,Xiaoxiao Wang,Jiehua Li,Xingguo Chen,Xingxing Jiang,Zheshuai Lin,Zhen Ma,Hongming Liu

A series of lanthanide-containing water-resistant nitrates, namely RE(OH)2NO3 (RE = Tb(1), Dy(2), Ho(3), and Er(4)), was obtained through the hydrothermal process. As possible nonlinear optical materials, they feature a layered isomorph composed of an [REO3(OH)6] polyhedron and an [NO3] triangle, and the synergistic arrangement of the [REO3(OH)6] and [NO3] groups in their structures leads to their obvious second-order nonlinear optical effect. Nevertheless, the unique optical absorption caused by the electronic transitions on 4f–4f orbitals of lanthanides results in their second harmonic generation responses of different strengths, with 1 exhibiting 5.07 times that of KDP, but 2–4 showing less than half of KDP. In addition, 1 possesses an outstanding water-resistant capacity and a transparent cut-off edge around 300 nm, foreshadowing its potential value as a nonlinear optical crystal. Moreover, 1 is found to emit characteristic green fluorescence due to the typical 5D4 → 7F5 transitions of the excited Tb3+ ions

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Construction of Phlorotannin-Based Nanoparticles for Alleviating Acute Liver Injury

Fengxian Luo,Beiwei Zhu,Di Wu,Yu Xu,Tao Chen,Yanfei Li,Jiangning Hu

Acute liver injury (ALI) is a severe health condition with limited treatment options. Phlorotannin (PT), a natural compound extracted from seaweeds, has shown potential in improving liver function. However, its poor stability and bioavailability have limited its applications in vivo. In this study, we developed PT-based nanoparticles (NPs) through a Mannich reaction with glycine, which exhibited good biocompatibility and prolonged circulation time in vivo. Our results revealed that the PT NPs possess strong free radical scavenging ability, effectively reducing reactive oxygen species (ROS) and alleviating oxidative stress and proinflammatory responses in the H2O2-induced oxidative damage model of HepG2 cells. Furthermore, the PT NPs effectively attenuated oxidative stress and inflammation in the liver tissue of carbon tetrachloride (CCl4)-induced liver injury mice by regulating the Nrf2/HO-1 signaling pathway. In summary, our results suggested that the PT NPs could serve as a promising nano-therapeutic strategy for alleviating ALI.

研究领域: 药理学 · 纳米技术 · 肝病学
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PHYTOMEDICINE · 2025 · IF 8.3

Atraric Acid Attenuates Chronic Intermittent Hypoxia-Induced Brain Injury via AMPK-Mediated Nrf2 and FoxO3a Antioxidant Pathway Activation

Mengxin Li,Jun Wang,Zihan Xu,Yue Lin,Jingquan Dong

Background Obstructive sleep apnea syndrome (OSAS), a chronic disorder affecting approximately 10% of adults worldwide with heightened prevalence in males and obese populations, induces irreversible neurocognitive impairment. Atraric Acid (AA), a natural depside compound derived from lichens, exhibits dual functional properties through its molecular groups capable of free radical scavenging and metal chelation. However, its therapeutic potential in OSAS-related pathologies remains unexplored. Objective This study aims to investigate the neuroprotective effects and molecular mechanisms of AA against CIH-induced neuronal damage. Methods CIH mouse models and hypoxic injury models in HT22 neurons were established. AA was administered to mice at doses of 5, 10, and 20 mg/kg (selected based on literature references and preliminary experiments), and to cells at an optimal concentration of 20 μM (determined by CCK-8 assays). Therapeutic efficacy was evaluated through behavioral tests including the Morris Water Maze, Elevated Plus Maze, and Open Field Test. Neuroprotective effects were assessed via histopathological examination (e.g., neuronal survival in hippocampal CA3 and DG sub-regions) and detection of oxidative stress/ferroptosis markers (e.g., MDA levels, GPX4 expression, and related biomarkers). Transcriptomic sequencing and molecular docking analyses were employed to investigate differentially expressed genes, pathway enrichment, and underlying mechanisms. Results In vivo and in vitro experiments demonstrated that AA significantly alleviated neuronal damage in CIH mice and enhanced HT22 cell viability. AA down-regulated oxidative stress- and ferroptosis-related gene expression. Transcriptomic sequencing identified AMPK signaling as a key target. Combined AMPK inhibitor (Compound C) and nuclear-cytoplasmic fractionation experiments confirmed that AA synergistically regulates dual antioxidant pathways (Nrf2/HO-1 and FoxO3a/SOD2) via AMPK activation. Conclusion AA mitigates CIH-induced neurocognitive impairment by AMPK-dependent activation of the Nrf2/HO-1 and FoxO3a/SOD2 axes, establishing a dual antioxidant-ferroptosis defense barrier. This study is the first to systematically elucidate AA's molecular mechanisms using transcriptomics data integrated with computational simulations, providing novel therapeutic targets and a translational paradigm for developing natural compound-based therapies for OSAS.

CAS / MDL: 4707-47-5
研究领域: 神经生物学 · 睡眠医学 · 分子药理学 · 氧化应激 · 信号转导 · 转化医学 · 天然产物药理学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 14 ·6666 · IF 4.9

Kaempferol Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice by Regulating Intestinal Short-Chain Fatty Acids

Siqi Zhang,Fei Tang,Zhe Zhou,Linhui Li,Yang Tang,Kaiwen Fu,Yang Tan,Ling Li

Liver fibrosis remains a critical health concern with limited therapeutic options. Kaempferol (Kae) is a natural flavonoid widely present in natural plants, yet its role in modulating gut–liver axis interactions during fibrosis is unexplored. This study investigates the hepatoprotective effects of Kae on alleviating carbon tetrachloride (CCl4)-induced liver fibrosis, and its underlying mechanisms, focusing on oxidative stress, gut microbiota, and short-chain fatty acids (SCFAs), are revealed. A mouse model of hepatic fibrosis was built by the subcutaneous injection of CCl4. Meanwhile, Kae was administered by gavage at doses of 25, 50, and 100 mg/kg body weight. Serum biomarkers, liver histopathology, oxidative damage markers, and nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling were analyzed. AML12 hepatocytes were pretreated with Kae or SCFAs (acetate, propionate, butyrate) before H2O2-induced oxidative injury. The changes in gut microbiota and the levels of SCFAs were assessed via 16S rRNA sequencing and GC-MS, respectively. Kae effectively alleviated the destruction of the liver morphology and tissue structure, reduced the infiltration of inflammatory cells, collagen deposition in the liver, and the expression of fibrotic factors, and downregulated the oxidative stress level in the liver of mice with liver fibrosis by activating the Nrf2/Keap1/HO-1 pathway (p< 0.05 or 0.01). In vitro, Kae significantly mitigated H2O2-induced cytotoxicity and oxidative damage (p< 0.05 or 0.01). Furthermore, Kae restored gut microbiota diversity, increased beneficial genera (e.g.,Lactobacillus), and elevated both intestinal and hepatic SCFA levels (p< 0.01). The discrepant SCFA pretreatment similarly protected AML12 cells by activating Nrf2 signaling (p< 0.05 or 0.01). Our research suggests that Kae could inhibit CCl4-induced liver fibrosis by restoring the levels of intestinal metabolite SCFAs to reduce oxidative damage.

研究领域: 药理学 · 肝脏病学 · 微生物学 · 生物化学 · 分子生物学 · 营养科学
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Drug Design Development and Therapy · 2025 · IF 5.1

Magnesium Isoglycyrrhizinate Alleviates Alectinib-Induced Hepatotoxicity by Inhibiting Mitochondrial Damage-Mediated Pyroptosis

Yizhang Chen,Chenxiang Wang,Yuna Wu,Yuhan Zeng,Shangjing Xie,Jialu Weng,Lei Guo,Jing Fu,Tao Zhou,Xiuhua Zhang,Ziye Zhou

Introduction Alectinib is a widely used first-line ALK inhibitor for fusion-positive non-small cell lung cancer. However, its clinical use is limited by hepatotoxicity, and its mechanism remains unclear. This study aims to elucidate how alectinib induces liver injury and to explore a potential protective strategy.Methods In vitro, AML-12 hepatocytes were incubated with alectinib to determine cell viability and morphology by using CCK-8 assay and optical microscopy, respectively. Necrosis was assessed by flow cytometry after Annexin V-FITC/PI staining. Mitochondrial damage was analyzed by measuring membrane potential, ultrastructure, and respiratory chain complex activities using JC-1 staining under fluorescence microscopy, transmission electron microscopy, and assay kits, respectively. Intracellular reactive oxygen species (ROS) levels were detected using DCFH-DA staining and flow cytometry. Pyroptosis- and oxidative stress-related proteins (NLRP3, GSDMD-N, P20, cleaved IL-1β, Nrf2, HO-1) were quantified by Western blot. In vivo, C57BL/6J mice were divided into control, alectinib treatment, and alectinib plus magnesium isoglycyrrhizinate (MgIG) treatment groups. Serum ALT and AST were measured to assess liver function. Hepatic oxidative stress was evaluated by SOD and MDA levels. Inflammatory cytokines including IL-1β and TNF-α were measured by corresponding kits. Liver histopathology was examined by hematoxylin-eosin staining.Results We found alectinib could induce the death of AML-12 hepatocytes. Alectinib impaired both the function and structure of mitochondria and caused a significant increase in ROS levels. The excessive accumulation of ROS triggered oxidative stress and finally resulted in cell pyroptosis in AML-12 cells. MgIG was found to alleviate mitochondrial damage and reduce ROS levels, restore the Nrf2/HO-1 signaling pathway, thereby inhibiting oxidative stress and pyroptosis caused by alectinib.Conclusion Alectinib induces elevated ROS levels in hepatocytes by damaging mitochondria and causing oxidative stress in hepatocytes, which results in cell pyroptosis and ultimately hepatotoxicity, whereas MgIG can treat alectinib-induced hepatic injury by restoring mitochondrial function and structure.

CAS / MDL: 1256580-46-7
研究领域: 药理学 · 毒理学 · 细胞生物学 · 肿瘤学 · 分子生物学
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JOURNAL OF VIROLOGY · 2025 · IF 3.8

Self-assembled cyanidin-3-O-glucoside nanoparticles alleviate inflammation and ferroptosis induced by PRRSV infection

Xiaohan Chen,Yipeng Pang,Fructueux Modeste Amona,Zilu Liu,Fang Wang,Yuan Liang,Jiachen Yang,Wanhan Zhang,Xingtang Fang,Xi Chen

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen that causes substantial economic losses in the global swine industry, primarily by impairing reproductive performance and respiratory health. However, current therapeutic approaches remain limited in effectively controlling PRRSV infection. Here, we present self-assembled cyanidin-3-O-glucoside (C3G)-based nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent against PRRSV infection. These nanoparticles demonstrated excellent stability and biocompatibility, with minimal cytotoxicity in Marc-145 cells. C3G-Cs-SeNPs significantly reduced ROS levels in PRRSV-infected cells, enhancing the antioxidant capacity and mitigating oxidative stress. In addition, they effectively inhibited key stages of the PRRSV lifecycle, including viral internalization and replication, leading to a marked decrease in viral proliferation. Moreover, C3G-Cs-SeNPs alleviated ferroptosis by restoring redox homeostasis through enhanced antioxidant enzyme activity. Mechanistically, these nanoparticles potentially activate the SIRT1/Nrf2/HO-1 signaling pathway, which plays a critical role in regulating inflammation and ferroptosis in PRRSV-infected cells. These findings suggest that C3G-Cs-SeNPs could serve as a novel therapeutic approach to modulate inflammation, ferroptosis, and viral replication in respiratory viral infections. Our study highlights the therapeutic potential of C3G-Cs-SeNPs in combating PRRSV infection, with important implications for viral infection management and respiratory disease treatment.

CAS / MDL: 7084-24-4
研究领域: 病毒学 · 纳米技术 · 免疫学 · 抗病毒治疗 · 氧化应激研究
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ACS Photonics · 2024 · IF 6.5

Ultraviolet and White Light Emissions from Multiphoton Upconversion Transitions in Yb/Tm/Ho Codoped Cubic Zirconia Single Crystals Excited by NIR

Wenxia Wu,Yazhao Wang,Limin Wu,Huiting Zhang,Zhonghua Zhu,Shengdi Ta,Peng Zhang,Shoulei Xu,Bernard A. Goodman,Wen Deng

Under excitation at 980 nm, Tm3+ may emit ultraviolet, blue, and red light, and Ho3+ may emit green light through multiphoton upconversion processes in Yb/Tm/Ho codoped materials. However, because the probability of the electron population of the higher excited state energy levels is much lower than that of the lower ones in multiphoton upconversion processes, it is difficult to observe the ultraviolet emission of Tm3+-doped single crystals under excitation at 980 nm. Here, we report that high-quality single crystals of cubic ZrO2 codoped with Tm2O3, Ho2O3, and Yb2O3 are successfully grown by the optical floating zone method, and ultraviolet emission at 308 nm was observed for the first time from multiphoton upconversion transitions in these highly transparent, low phonon energy single crystals under excitation at 980 nm. This result demonstrates the prospect of making ultraviolet solid-state lasers pumped by near-infrared light. Moreover, bright white light was emitted from the single crystal prepared with 5.00 mol % Yb2O3, 0.75 mol % Tm2O3, 0.0075 mol % Ho2O3, 2.2425 mol % Y2O3, and 92.00 mol % ZrO2 under excitation at 980 nm, and a bright solid white light source excited by a near-infrared light-emitting diode for practical use is presented.

研究领域: 材料科学 · 光学
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Materials Today Communications · 2024 · IF 3.7

Calcination-assisted hydrothermal crystallization and comparative up-/down-conversion luminescence of RE3+ (RE=Ho, Er and Tm)-doped YbNbO4 and Yb3NbO7

Bingxin Yuan,Meiting Li,Chi Zhang

The RE 3+ doped YbNbO 4 and Yb 3 NbO 7 nanophosphors (RE=Ho, Er and Tm) were synthesized via a calcination-assisted hydrothermal procedure. YbNbO 4 intensified almost the whole up-conversion (UC)/down-conversion (DC) emissions of RE 3+ by ∼2 times when compared with Yb 3 NbO 7 components, indicating that a lower symmetry environment in the former case is more favorable for photoluminescence. UC luminescence in each case was dominated by a green band at ∼539 nm for Ho 3+ and a NIR band at ∼803 nm for Tm 3+ , while doping YbNbO 4 and Yb 3 NbO 7 with Er 3+ separately yielded the slightly stronger green 556 nm and red 658 nm emissions. The UC/DC luminescence mechanisms were elaborated via Yb 3+ → RE 3+ forward/backward energy transfer and cross relaxation.

研究领域: 材料科学 · 光学
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