International Journal of Nanomedicine
·
2024
·
IF 6.6
Tingting Chen,Zimei Wu,Qiaodan Hou,Yixin Mei,Kunkun Yang,Jing Xu,Lin Wang
Purpose Given the escalating prevalence of diabetes, the demand for specific bone graft materials is increasing, owing to the greater tendency towards bone defects and more difficult defect repair resulting from diabetic bone disease (DBD). Melatonin (MT), which is known for its potent antioxidant properties, has been shown to stimulate both osteogenesis and angiogenesis.Methods MT was formulated into MT@PLGA nanoparticles (NPs), mixed with sodium alginate (SA) hydrogel, and contained within a 3D printing polycaprolactone/β-Tricalcium phosphate (PCL/β-TCP) scaffold. The osteogenic capacity of the MT nanocomposite scaffold under diabetic conditions was demonstrated via in vitro and in vivo studies and the underlying mechanisms were investigated.Results Physicochemical characterization experiments confirmed the successful fabrication of the MT nanocomposite scaffold, which can achieve long-lasting sustained release of MT. The in vitro and in vivo studies demonstrated that the MT nanocomposite scaffold exhibited enhanced osteogenic capacity, which was elucidated by the dual angiogenesis effects activated through the NF-E2–related factor 2/Heme oxygenase 1 (Nrf2/HO-1) signaling pathway, including the enhancement of antioxidant enzyme activity to reduce the oxidative stress damage of vascular endothelial cells (VECs) and directly stimulating vascular endothelial growth factor (VEGF) production, which reversed the angiogenesis-osteogenesis uncoupling and promoted osteogenesis under diabetic conditions.Conclusion This study demonstrated the research prospective and clinical implications of the MT nanocomposite scaffold as a novel bone graft for treating bone defect and enhancing bone fusion in diabetic individuals.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Song-Xue Yang,Wei-Lie Xiao,Xing-Jie Zhang
Ethnopharmacological relevance The root of Saposhnikovia divaricata has been traditionally used in Chinese medicine to treat inflammation and immune related skin diseases, such as skin allergy and itchy rash. However, scientific research supporting its efficacy, particularly in curing inflammation from acne, is still scarce. Aim of the study To evaluate the therapeutic effects of essential oil of Saposhnikovia divaricata (EOSD) on Cutibacterium acnes ( C. acnes )-induced acne and investigate its mechanisms. Materials and Methods An acute acne model was established by injecting C. acnes into mouse ears, followed by topical EOSD treatment (0.25 %, 0.5 % and 1 %). Ear tissues were analyzed 24 hours post-treatment. In vitro, C. acnes -stimulated J774A.1 macrophages were treated with EOSD (3, 10 and 30 μg/ml) to assess mitochondrial damage, oxidative stress, and inflammatory responses. Key markers were analyzed using electron microscopy, real-time PCR, immunoblotting, ELISA, and immunofluorescence. Nrf2 knockdown was achieved via siRNA transfection. Results C. acnes suppressed Nrf2 activation, increased ROS levels, and triggered NLRP3 inflammasome activation, leading to inflammation. EOSD restored Nrf2 activity, reduced ROS levels, and inhibited NLRP3 activation. In vitro, EOSD disrupted Nrf2/Keap1 interaction, enhanced Nrf2 nuclear translocation, reduced mitochondrial damage, and suppressed pyroptosis by downregulating IL-1β, Caspase-1, GSDMD, and NF-κB signaling. These effects were reversed by Nrf2 knockdown. Conclusion EOSD alleviates oxidative stress and modulates NLRP3 inflammasome activation through upregulating Nrf2 pathway and inhibiting NF-κB pathway, as well as improving mitochondrial homeostasis and inflammatory responses in acne. These findings suggest that EOSD may be a promising therapeutic agent for the treatment of acne vulgaris.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2020
·Vol. 9
·期 9
·783
·
IF 5.014
Bowen Sun,Xifan Wang,Xiaoxue Liu,Longjiao Wang,Fazheng Ren,Xiaoyu Wang,Xiaojing Leng
Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFβ/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.Keywords:hippuric acid;protein-bound uremic toxin;renal fibrosis;oxidative stress;antioxidation;NRF2;NRF2 ubiquitination
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Hao Zhang,Yi Zhao,Jia-Gen Cui,Xue-Nan Li,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis.
研究领域:
毒理学
·
心脏病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Rui Li,Jiaojiao Mou,Lei Zhao,Mengqiu Hu,Bin Wang,Yanying Sun,Jing Liu,Xiaohui Qi,Jie Yang
Intestinal barrier disruption and oxidative stress are the major pathological features during the ulcerative colitis (UC). The present research aimed to explore the amelioration property of fucoidan of Stichopus chloronotus (Fuc Sc) against dextran sulfate sodium (DSS) resulted UC. The findings from our study suggest that treating with Fuc-Sc improved the integrity of the Caco-2 monolayer through raising its TEER value, reducing LDH release, promoting the tight junction proteins (TJs) in Caco-2 cells, and shielding the cells from decreases of these proteins caused by H 2 O 2 . Besides, Fuc-Sc activated Nrf2/HO-1 pathway to facilitate the antioxidant activities of Caco-2 cells under oxidative stress through elevating the SOD and GSH, and reducing LDH and MDA. Furthermore, oral administration of Fuc-Sc attenuated DSS resulted body weights decrease, DAI score increase, colon length decrease, and structural damage of colon tissue. Fuc-Sc also promoted the barrier function and suppressed oxidative injury via activation of Nrf2/HO-1 signal pathway. Collectively, this research provided the theoretical foundation for fucoidan as a promising functional food for colitis.
研究领域:
营养学
·
消化病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2025
·Vol. 40
·期 5
·1-14
·
IF 3.5
Zhao Hexiang,Yang Ping,Zhang Mou,Zheng Wenshu,Qi Renli,Zhu Xiaofeng,Li Jinghui,Li Shipeng
Reperfusion, while essential for restoring blood supply, paradoxically exacerbates neuronal damage through cerebral ischemia-reperfusion injury (CIRI). This study aimed to develop a reactive oxygen species (ROS)-responsive drug delivery system (DDS) loaded with edaravone (EDA) to enhance targeted therapy for CIRI. The stimuli-responsive DDS was synthesized using dextran (DEX) as the biocompatible carrier and benzeneboronic acid pinacol ester (BAPE) as the ROS-sensitive moiety. The physicochemical characteristics of the DEX-BAPE/EDA (DB/EDA) micelles were systematically evaluated. In vitro studies assessed the anti-inflammatory, antioxidant, and anti-apoptotic effects of DB/EDA. Moreover, the neuroprotective efficacy of DB/EDA in vivo was analyzed via behavioral tests, infarct volume measurement, ELISA assays of inflammatory cytokines and OS markers, and Western blot analysis of Nrf2-related pathways. Pharmacokinetics and biosafety were analyzed through plasma profiling and H&E staining. DB/EDA exhibited high stability, efficient drug encapsulation, and ROS-responsive drug release. Cellular uptake studies confirmed enhanced internalization of DB/EDA micelles in BV2 cells. In the oxygen-glucose deprivation/reoxygenation (OGD/R) model, DB/EDA significantly suppressed TNF-α, IL-1β, IL-6, and MDA, restored SOD levels, and attenuated apoptosis. In the middle cerebral artery occlusion/reperfusion (MCAO/R) mice, DB/EDA administration effectively improves cognition and mitigates neuronal damage. Mechanistically, DB/EDA activated the Nrf2/HO-1 pathway, amplifying antioxidant and anti-inflammatory responses. Pharmacokinetic analysis revealed prolonged circulation and increased brain accumulation, and histopathological analysis demonstrated the safety profile of DB/EDA. The ROS-responsive DB/EDA nano-micelles provided targeted EDA delivery to ischemic brain regions, alleviating CIRI via Nrf2 activation, suggesting that DB/EDA is a promising strategy for CIRI treatment. Graphical abstract
研究领域:
药剂学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2025
·
IF 5.7
Lulu Chen,Bicheng Chen,Xiang Su
An abdominal aortic aneurysm (AAA) is a life-threatening vascular condition characterized by the dilation of the abdominal aorta, with ferroptosis playing a significant role in its pathogenesis. This study investigates the therapeutic potential of engineering biomimetic nanovesicles to deliver phosphatidylethanolamine-binding protein 1 (PEBP1) mRNA for inhibiting ferroptosis in vascular smooth muscle cells (VSMCs) and preventing AAA progression. Differential gene expression analysis of the AAA transcriptomic dataset GSE57691 identified 243 differentially expressed genes (DEGs), intersecting with 12 ferroptosis-related genes. Single-cell analysis of dataset GSE237230 highlighted PEBP1 as a key gene in VSMCs. Overexpression of PEBP1 in VSMCs enhanced proliferation, reduced reactive oxygen species (ROS) and iron levels, and inhibited apoptosis and ferroptosis via the NRF2/GPX4 axis. The engineered biomimetic nanovesicles demonstrated significant uptake by VSMCs and effective delivery of PEBP1 mRNA. In vivo studies confirmed that these nanovesicles substantially inhibited AAA progression in mice. This study presents a novel bioengineering approach for AAA treatment by targeting ferroptosis through PEBP1 mRNA delivery, offering a promising molecular strategy for the prevention and management of AAA.
研究领域:
生物医学工程
·
纳米技术
·
分子生物学
·
心血管疾病研究
·
基因治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Physiology
·
2025
·
IF 3.4
Yi-Jia Liu,Jian Guo,Chang-Da Li,Si-Yin Han,Lu Cai
Introduction Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Methods Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. Results The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Discussion Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine’s role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Food Measurement and Characterization
·
2024
·
IF 2.9
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.
研究领域:
食品科学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Cell Communication and Signaling
·
2025
·Vol. 23
·期 1
·1-21
·
IF 8.9
Jia Yifan,He Muchen,Wang Fan,Zhan Yaqing,Deng Qiwen,Shen Jiantong,Wang Xiwen,Ran Qi,Huang Wenqi,Ling Yihong,Wen Shihong
Background & Aims Dysfunction of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) contributes to the development of intestinal ischemia/reperfusion (IR) injury. Tryptophan (TRP), an essential amino acid, plays a crucial role in maintaining intestinal homeostasis, yet its regulatory effects on the GVB following IR remain unexplored. We aimed to better define the role of TRP in intestinal IR in vivo and in vitro. Methods Mice underwent intestinal ischemia/reperfusion (IR) and were fed control, TRP-recommended (TRP-r), or TRP-sufficient (TRP-s) diets. Fecal metagenomic sequencing analyzed microbial composition, and targeted metabolomics quantified tryptophan and its metabolites in intestinal and serum samples. ILA’s effects on barrier integrity were assessed via tight junction protein expression and FITC-dextran permeability assays. RNA sequencing of intestinal endothelial cells elucidated mechanisms by which ILA modulated GVB function. The STAT3-claudin 2 relationship was validated in vitro by ChIP-qPCR. Results TRP supplementation significantly reshaped the gut microbiota, mitigated tissue damage and enhanced the integrity of both the IEB and GVB. Indole-3-lactic acid (ILA), a key tryptophan metabolite, was identified as an important factor in preserving GVB function. Mechanistically, our results show that the aryl hydrocarbon receptor (AhR)/Nrf2/signal transducer and activator of transcription 3 (STAT3) pathway is essential for ILA-mediated improvement of GVB integrity and downregulation of the pore-forming protein claudin 2. Conclusions Our findings highlight the dual role of ILA in reinforcing both IEB and GVB functions and shed light on the molecular mechanisms underlying ILA’s GVB-protective effects. This study implicates that ILA or other AhR-activating metabolites may serve as promising pharmacological agents for alleviating IR-induced intestinal damage. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2025
·
IF 2.5
Jie Liu,Yuan-Yuan Xu,Tian-Ye Gao
Background Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury. Methods In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity. Results Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan. Conclusions Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.
研究领域:
药理学
·
肾脏病学
·
分子生物学
·
中医中药
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Ruijing Li,Weili Yang,Lijuan Zheng,Xingxue Yan,Cuihua Liu,Yaodong Zhang,Jitong Li
Prenatal alcohol exposure is a leading cause of developmental abnormalities and neurobehavioral deficits, collectively known as fetal alcohol spectrum disorder (FASD). The underlying molecular mechanisms, however, are not fully elucidated, hindering the development of effective therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a key pathological process in various diseases. Gastrodin (GAS), the primary bioactive component of Gastrodia elata , has demonstrated potent antioxidant and neuroprotective properties. This study aimed to investigate the protective effects of GAS against alcohol-induced developmental and neurotoxic damage and to elucidate the underlying molecular mechanisms. Using a zebrafish larval model, we found that exposure to 200 mM alcohol from 2 to 24 hours post-fertilization (hpf) induced significant developmental toxicity, including a decreased hatching rate, body length and eye diameter, and increased morphological malformations in larvae. Alcohol-exposed larvae also exhibited severe neurobehavioral deficits, characterized by a reduction in movement distance and average velocity in dark conditions. Mechanistically, alcohol exposure triggered ferroptosis, evidenced by an increase in intracellular Fe 2+ , malondialdehyde (MDA), and reactive oxygen species (ROS) levels, alongside a decrease in the levels of glutathione (GSH) and reduced glutathione peroxidase 4 (GPX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) activities. Co-treatment with GAS (200 mg/L) significantly ameliorated these alcohol-induced developmental and neurobehavioral defects. GAS administration effectively suppressed the hallmarks of ferroptosis by restoring the ROS level and altering the expression of genes related to oxidative stress. In addition, GAS suppressed alcohol-induced cell apoptosis, downregulated caspase3b , bax , caspase8 , and upregulated bcl2 in mRNA levels. Molecular analysis revealed that GAS exerts its anti-ferroptotic effect by activating Nrf2/GPX4 signaling pathway, which was suppressed by alcohol. Our findings indicate that ferroptosis plays a key role in alcohol-induced developmental neurotoxicity, and GAS provides protection by activating the Nrf2/GPX4 axis. This suggests that GAS could be a potential therapeutic option for reducing the negative effects of prenatal alcohol exposure.
研究领域:
神经毒理学
·
发育生物学
·
分子药理学
·
氧化应激研究
·
斑马鱼模型
✓ 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）