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FASEB JOURNAL · 2022 ·Vol. 36 ·期 9 ·e22505 · IF 5.834

Curcumin activates Nrf2/HO-1 signaling to relieve diabetic cardiomyopathy injury by reducing ROS in vitro and in vivo

Xia Wu,Xueliang Zhou,Songqing Lai,Jichun Liu,Jianwei Qi

The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM). Nuclear factor erythroid2-related factor2 (Nrf2), a transcriptional activator, enhances its ability to resist oxidative stress by activating multiple downstream anti-oxidants, anti-inflammatory proteins, and detoxifying enzymes. However, the mechanism of Nrf2 signaling in HG-induced DCM is unclear. In this study, we used HG pretreated H9c2 cells as the experimental basis in vitro, and established a high fat-diet, streptozotocin (STZ) induced Type 2 diabetic rat model in vivo. Meanwhile, we used shRNA-Nrf2 and curcumin (CUR) (as an activator) to affect H9c2 cells, to verify the role of the Nrf2 signaling pathway in DCM. The results showed that the excessive production of ROS caused by HG, which could inhibit the activation of Nrf2-related signaling, resulting in a decrease in cell energy metabolism and an increase in cell apoptosis. Surprisingly, we found that the activation of the Nrf2 signaling pathway significantly increased cardiomyocyte viability, reduced ROS formation, increased antioxidant enzyme activity, and inhibited cardiomyocyte apoptosis. In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation.

CAS / MDL: 458-37-7
研究领域: 药理学 · 心脏病学 · 糖尿病研究 · 细胞生物学 · 分子生物学
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JOURNAL OF THE EUROPEAN CERAMIC SOCIETY · 2023 · IF 5.7

High-entropy rare earth phosphates (REPO4, RE = Ho, Tm, Yb, Lu, Dy, Er and Y) with excellent comprehensive properties

Peixiong Zhang,Enhui Wang,Chunyu Guo,Tao Yang,Xinmei Hou

High-entropy rare earth phosphates (HE REPO 4 , RE = Ho, Tm, Yb, Lu, Dy, Er and Y) with xenotime structure have been successfully synthesized and comprehensively characterized to evaluate their feasibility as thermal/environmental barrier coatings (T/EBCs) applied in SiC f /SiC ceramic matrix composites (SiC-CMCs). HE REPO 4 show good chemical compatibility with SiO 2 at 1400 °C and excellent high-temperature stability up to 1750 °C. The thermal expansion coefficient (TEC) of HE (6RE 1/6 )PO 4 is 5.9 × 10 −6 /°C ranging from room temperature to 900 °C, which is close to that of SiC-CMCs. Compared with single-component REPO 4 , the thermal conductivity of HE (6RE 1/6 )PO 4 (from 5.1 W·m −1 ·K −1 at 100 °C to 2.8 W·m −1 ·K −1 at 1300 °C) is significantly reduced benefiting from larger lattice distortion. These allow HE REPO 4 to be a potential candidate as T/EBCs applied in SiC-CMCs.

研究领域: 材料科学 · 陶瓷 · 涂层
✓ 已验证 DOI 高影响因子
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Journal of Food Measurement and Characterization · 2024 · IF 2.9

Extraction of edible DNA from Alaska pollock sperm and its preventative effects on alcohol-induced liver injury

Meng Wenya,Xue Yuhan,Zhang Jing,Wang Ye,Hou Hu,Li Jing,Dong Ping

Fish sperm extracts have been shown to have various activities, but it has not been effectively developed and utilized at present due to the lack of effective methods for preparing edible grade products. This study proposed a method for preparing edible fish sperm DNA from Alaska pollock (PSD) and evaluated the hepatoprotective effect of the extracted DNA. Firstly, the preparation conditions of fish sperm DNA were optimized by response surface methodology. Under the ideal conditions that the ratio of solid to liquid was 3:1, the pH of extractant was 7.5, the purified solvent was saturated sodium carbonate solution and absolute ethanol was twice the volume of purified solvent, the yield of PSD was (13.657 ± 0.577) µg/mg. To evaluate the liver protective effects of the extracted DNA, the digestion products by three digestion enzymes (pepsin, DNase I and DNase II) compared using an alcohol-induced HepG2 cell model. The DNase I hydrolysis product was more effective in preventing cell alcohol damage, as shown by reducing the content of lipid peroxides. Transcriptomics and metabolomics data revealed that the DNase I hydrolysis product activated the Nrf2/HO-1 pathway through the PI3K/Akt signaling pathway and regulated abnormal lipid synthesis through the steroidogenic pathway. This study will provide an important basis for the evaluation and analysis of the hepatoprotective effect of fish sperm DNA in vivo. Overall, our findings will promote the comprehensive utilization of fish sperm and other aquatic wastes, and provide scientific guidance for the development of functional nucleic acid foods.

CAS / MDL: 9025-64-3
研究领域: 食品科学 · 分子生物学 · 生物化学
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Scientific Reports · 2024 ·Vol. 14 ·期 1 ·1-15 · IF 3.8

Nrf2 depletion enhanced curcumin therapy effect in gastric cancer by inducing the excessive accumulation of ROS

Wang Yan,Wang Shasha,Ma Chenchen,Qi Weiwei,Lv Jing,Zhang Mengqi,Wang Shibo,Wang Rui,Lu Yangyang,Qiu Wensheng

Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.

CAS / MDL: 616-91-1
研究领域: 肿瘤学 · 药理学 · 分子生物学 · 癌症治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING · 2019 ·Vol. 125 ·期 11 ·1-8 · IF 1.784

Investigation of new color-tunable up-conversion phosphors and their long-persistent luminescence properties for potential biomedical applications

Zhou Xinquan,Ju Guifang,Dai Tiansong,Li Yang,Wu Haoyi,Hu Yihua

Long-persistent phosphor and up-conversion particles used for optical imaging continue to interest researchers. The present work identifies an Er 3+ doped micro-sized CSAO-CSO mixed material that exhibits both up-conversion and persistent luminescence. The cross-relaxation that occurs among Er 3+ ions contributes to enhancing the up-conversion intensity. The Tm 3+ /Ho 3+ co-doped strategy was used to induce tunable up-conversion colors. The cross-relaxation process corresponding to the energy transfer mechanism was investigated via the luminescence lifetimes of Er 3+ . Moreover, the persistent luminescence and thermo-luminescence properties of CSAO-CSO: Er 3+ were also investigated systematically. Our results combine the fields of up-conversion and persistent luminescence, which may support other explorations of new kinds of long-persistent and up-conversion materials.

研究领域: 材料科学 · 生物医学工程 · 光学成像
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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

Improving Fenton-like system with Catechin, an environmental-friendly polyphenol: Effects and mechanism

Zhongyi Fang,Jie Zhao,Yuan Li,Yu Wang,Tian Qiu,Yanlin Wu,Wenbo Dong,Gilles Mailhot

Fenton-like system had long been modified to promote its adaptability and efficiency by adding extra components like metal chelators or reducers. Nonetheless, chelator such as ethylene diamine tetraacetic acid (EDTA) was harmful in high dosage. While strong reducers could efficiently promote the generation speed of hydroxyl radicals (HO ), they could also get oxidized easily during storage time, for which further application was costly. In this study, (+)-catechin (CAT), an environmental- friendly component, was proved to be an efficient promoter of Fenton-like system on Bisphenol A (BPA) degradation. The modified system achieved 92% of BPA removal in one hour. The mechanism was studied, and the reaction procedure between CAT and Fe(III) together with the degradation pathways of CAT were identified. Fe(III) got chelated first by CAT and quickly reduced to Fe(II) via a single inner-compound electron transfer. The intermediates of CAT could further reduce one and a half more potion of Fe(III) on average. Consequently, massive amount of Fe(II) turned Fenton-like procedure to Fenton reaction and thus promoted the generation of HO . The main radicals contributed on BPA degradation was HO . BPA could be efficiently degraded at pH 6.5 or acidic pH range, but the degradation was completely inhibited with the pH higher than 8.0. The optimal mole ratio between Fe(III) and CAT was 6:1 and the degradation pathway of BPA was deduced.

CAS / MDL: 28048-33-1
研究领域: 环境化学 · 水处理 · 污染物降解 · 绿色化学
✓ 已验证 产品关联 DOI 高影响因子
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PHYTOMEDICINE · 2022 · IF 6.656

Protective effect of curcumin on hepatolenticular degeneration through copper excretion and inhibition of ferroptosis

Xun Sun,Xinyu Zhang,Hui Yan,Hongfei Wu,Shijian Cao,Wenchen Zhao,Ting Dong,An Zhou

Background Hepatolenticular degeneration (HLD) is an autosomal recessive disorder concerning copper metabolism . Copper overload is also accompanied by iron overload in HLD patients , which can lead to ferroptosis . Curcumin , the active component in turmeric, has the potential to inhibit ferroptosis. Purpose The current study proposed a systematic investigation of the protective effects of curcumin against HLD and the underlying mechanisms. Methods The protective effect of curcumin on toxic milk (TX) mice was studied. Liver tissue was observed via hematoxylin-eosin (H&E) staining and the ultrastructure of the liver tissue was observed through transmission electron microscopy . Copper levels in the tissues, serum, and metabolites were measured by atomic absorption spectrometry (AAS). In addition, serum and liver indicators were evaluated. In cellular experiments, the effect of curcumin on the viability of rat normal liver cells (BRL-3A) was determined via the 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell and mitochondrial morphology were observed in curcumin-mediated HLD model cells. The intracellular copper ion fluorescence intensity was observed via fluorescence microscopy , and intracellular copper iron content was detected using AAS. Further, oxidative stress indicators were evaluated. Cellular reactive oxygen species (ROS) and cellular mitochondrial membrane potential were examined via flow cytometry. Furthermore, the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) were determined via western blotting (WB). Results The histopathology of the liver confirmed the hepatoprotective effects of curcumin. Curcumin improved copper metabolism in TX mice. Both serum liver enzyme markers and antioxidant enzyme levels indicated the protective effect of curcumin against HLD-related liver injury. The MTT assay results showed that curcumin was protective against excess copper-induced injury. Curcumin improved the morphology of HLD model cells and their mitochondrial morphology. The Cu 2+ fluorescent probe and the AAS results indicated that curcumin reduced Cu 2+ content in HLD hepatocytes. In addition, curcumin improved oxidative stress levels and prevented the decline of mitochondrial membrane potential in HLD model cells. The ferroptosis inducer Erastin reversed these effects of curcumin. WB revealed that curcumin promoted Nrf2, HO-1, and GPX4 protein expression in HLD model cells, and the Nrf2 inhibitor ML385 reversed the effects of curcumin. Conclusion Curcumin demonstrates a protective role by expelling copper and inhibiting ferroptosis, activating the Nrf2/HO-1/GPX4 signaling pathway in HLD.

CAS / MDL: 52-67-5
研究领域: 药理学 · 毒理学 · 分子生物学 · 细胞生物学 · 神经病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROSCIENCE · 2025 · IF 2.8

Formononetin attenuates LPS-induced neuroinflammation and depressive-like behaviors by regulating the Keap1/Nrf2/HO-1 pathway in the hippocampus

Siqi Quan,Mengyuan Li,Zhouli Yue,Hui Liu,Shuaijun Peng,Roujia Guo,Xiaoyan Fang,Yucheng Li

Neuroinflammation and oxidative stress are major pathogenic drivers of depression, with the Keap1/Nrf2/HO-1 pathway serving as a key regulator of both processes. Formononetin (FMN) is a naturally occurring isoflavone with anti-inflammatory and antioxidant activities; however, its potential to exert antidepressant effects through activation of this pathway has not been investigated. In this study, lipopolysaccharide (LPS, 1 mg/kg, i.p.) was used to induce neuroinflammation and depressive-like behaviors in mice, and FMN (20 or 40 mg/kg) was administered for seven days prior to LPS challenge. FMN dose-dependently alleviated LPS-induced behavioral deficits, including reduced sucrose preference, decreased locomotor activity, and prolonged immobility in the tail suspension test. Hematoxylin-eosin (HE) and Nissl staining revealed that FMN markedly attenuated LPS-induced hippocampal neuronal damage. FMN also inhibited microglial activation, as evidenced by reduced Iba-1 expression, decreased NF-κB phosphorylation, and downregulation of both mRNA and protein levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Furthermore, LPS-induced lipid peroxidation was significantly attenuated, as indicated by lower levels of 4-hydroxynonenal (4-HNE). Molecular docking suggested a potential direct interaction between FMN and Keap1, while Western blot analysis confirmed that FMN downregulated Keap1 and upregulated Nrf2 and HO-1 protein expression. Collectively, these findings demonstrate that FMN alleviates LPS-induced neuroinflammation and depressive-like behaviors, likely through activating the Keap1/Nrf2/HO-1 pathway, supporting its potential as a preventive candidate for inflammation-associated depression.

CAS / MDL: 75-80-9
研究领域: 神经药理学 · 分子生物学 · 精神病学 · 炎症研究 · 氧化应激
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2013 ·Vol. 1 ·期 10 ·1491-1500 · IF 0

Magnetic γ-Fe2O3@REVO4 (RE = Sm, Dy, Ho) affinity microspheres for selective capture, fast separation and easy identification of phosphopeptides

Zhi-Gang Wang,Gong Cheng,Yan-Lin Liu,Ji-Lin Zhang,De-Hui Sun,Jia-Zuan Ni

The multifunctional microspheres consisting of the magnetic γ-Fe2O3 core and the affinity REVO4 (RE = Sm, Dy, Ho) shell have been synthesized via the homogenous precipitation–calcination–ion exchange three-step synthetic route. Their morphologies, structures, surface properties, and magnetisms were characterized, respectively. SEM and TEM images indicate that they all have an average size of about 400 nm and very rough surfaces. The TEM images further reveal that the γ-Fe2O3@REVO4 microspheres are all core–shell structures and the REVO4 shells are about 55–60 nm in thickness. The XRD pattern analyses show that the magnetic γ-Fe2O3 cores belong to cubic structure and the REVO4 (RE = Sm, Dy, Ho) shells are composed of their corresponding tetragonal major phases. HRTEM images, FTIR spectra and EDS further demonstrate the formations of tetragonal REVO4 shells based on checkup of the corresponding lattice fringes, characteristic IR absorption peaks and element signals. Their potentials for selective capture, rapid separation, and convenient mass spectra (MS) labeling of the phosphopeptides from complex proteolytic digests are explored and evaluated for the first time. The experimental results show that the magnetic γ-Fe2O3@REVO4 core–shell structured microspheres have high selective affinity for the phosphopeptides. The trapped phosphopeptides can be rapidly isolated by an external magnetic field, and can be easily identified by characteristic MS signals from 80 Da mass losses in the mass spectra (MS). Additionally, the γ-Fe2O3@REVO4 affinity materials can be reused after recovery.

研究领域: 材料科学 · 分析化学 · 生物化学
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Frontiers in Pharmacology · 2026 · IF 5.4

Licochalcone B suppresses oxidative stress and apoptosis accompanied by upregulating Nrf2/HO-1 pathway to ameliorate diabetic nephropathy in mice

Shan Luo,Yake Lan,Ruoqi Zhang,Zhongqiu Luan

Introduction Diabetic nephropathy (DN), as a complication of diabetes, is one of the major causes of end-stage renal disease. Licochalcone B (LCB), a flavonoid active component derived from licorice, is well known for its anti-inflammatory and antioxidant properties. However, the influence of LCB on DN remains unclear. This research investigated the effect of LCB on DN and elucidated the regulatory mechanism. Methods We employed male C57BL/6 mice to construct a DN mouse model induced by a high-fat diet (HFD)/streptozotocin (STZ). In vitro , a high glucose (HG)-induced injury model in HK-2 (human renal tubular epithelial) cells was used to further confirm the protective effects of LCB. Results LCB treatment (20 mg/kg and 40 mg/kg) decreased blood glucose levels, kidney injury, glycogen deposition, and collagen accumulation in the DN mice. Moreover, LCB at a dosage of 40 mg/kg reduced albumin, creatinine, and blood urea nitrogen levels by about 70.7%, 33.4%, and 45.6%, respectively, indicating an improvement in kidney function. In renal tissues, LCB suppressed oxidative stress and apoptosis in HFD/STZ-induced mice. Consistent with in vivo findings, LCB alleviated HG-induced oxidative stress and apoptosis in HK-2 cells. Transcriptome analysis revealed that LCB affects oxidative stress and renal function-related pathways to alleviate DN. Further mechanistic studies demonstrated that LCB treatment upregulates the expressions of heme oxygenase-1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), suggesting activation of the Nrf2/HO-1 signaling pathway. Conclusion Taken together, this research demonstrates that LCB suppresses oxidative stress and apoptosis accompanied by modulating the Nrf2/HO-1 pathway to ameliorate DN, which provides a promising strategy for DN treatment.

CAS / MDL: 1330-20-7
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INORGANIC CHEMISTRY · 2024 · IF 4.3

Structure and Magnetic Properties of a Family of Two-Leg Spin Ladder Compounds Ba2RE2Ge4O13 (RE = Pr, Nd, and Gd–Ho)

Jin Zhou,Andi Liu,Fangyuan Song,Langsheng Ling,Jingxin Li,Wei Tong,Zhengcai Xia,Gaoshang Gong,Yongqiang Wang,Jinkui Zhao,Hanjie Guo,Zhaoming Tian

Compared with the intensive investigation on 3d transition metal (TM)-based spin ladder compounds, less attention has been paid to the ones constructed by rare earth (RE) ions. Herein, we report a family of RE-based spin ladder compounds Ba2RE2Ge4O13 (RE = Pr, Nd, Gd–Ho) crystallized into a monoclinic structure with the space group C2/c. The RE ions are arranged on a two-leg spin ladder motif along the b-axis, where the rung and leg exchange interactions are bridged via RE–O–RE pathways and RE–O–Ge–O–RE routes, respectively. Moreover, the much shorter rung distance in RE2O12 dimer units than the leg distance suggests that Ba2RE2Ge4O13 compounds are strong-rung spin ladder systems. All of the synthesized Ba2RE2Ge4O13 (RE = Pr, Nd, Gd–Ho) compounds exhibit dominant antiferromagnetic (AFM) interactions and the absence of magnetic order down to 1.8 K. Among the family members, Ba2Dy2Ge4O13 can be described by Jeff = 1/2 Kramers doublet states, and the low-temperature specific heat indicates the coexistence of the spin-dimerized state with a broad maximum at ∼2.4 K and long-range AFM order with TN = 0.81 K. This family of Ba2RE2Ge4O13 compounds thereby provides a rare platform to investigate the novel spin ladder physics constructed by 4f electrons.

研究领域: 凝聚态物理 · 磁学 · 无机化学 · 量子材料
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ENVIRONMENTAL POLLUTION · 2026 · IF 7.2

Dibutyl phthalate exposure-induced AhR activation drives ferroptosis and HMGB1/TLR4-mediated inflammatory liver injury via NRF2–HO-1 signaling

Zixu Li,Muge Xu,Yahan Zhang,Yao Chen,Weiwei Feng,Ting Zhao,Liuqing Yang,Guanghua Mao,Xiangyang Wu

The widespread presence of plastic pollutants, particularly phthalate esters such as dibutyl phthalate (DBP), poses a significant threat to both ecosystems and human health. Despite the accumulating evidence of DBP toxicity, the mechanisms driving DBP-induced hepatotoxicity remain poorly understood. In this study, an integrated approach combining network toxicology, molecular docking, and multidimensional experimental validation was applied to elucidate the molecular pathways through which DBP causes liver damage. Ferroptosis was identified as a central player in DBP-induced hepatotoxicity. The results showed that DBP activates the aryl hydrocarbon receptor (AhR), regulating the NRF2/HO-1 signaling axis, which in turn induces iron overload and lipid peroxidation. Furthermore, ferroptotic hepatocytes release high-mobility group box 1 (HMGB1), activating the TLR4/NF-κB pathway in macrophages and amplifying inflammatory responses that exacerbate liver injury. Crucially, inhibition of either AhR expression or ferroptosis significantly attenuated these changes, highlighting the potential of AhR and ferroptosis as therapeutic targets. Together, these findings establish a novel mechanistic framework for DBP-induced hepatotoxicity: the AhR–NRF2/HO-1–ferroptosis–HMGB1/TLR4 axis. This study advances our understanding of plasticizer toxicity and offers insights for risk assessment and intervention strategies for combating environmental hepatotoxins.

✓ 已验证 DOI PubMed 高影响因子
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