INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 4.7
Tianxiao Hu,Jiayu Qi,Yinuo Xu,Jia He,Qingying Tan,Jie Hao,Jing Wang,Jiewei Hong,Jianwei Wang,Lin Chen,Xiaobing Dou
This study aims to investigate the molecular mechanisms by which 4-hydroxynonenal (4-HNE) regulates hydrogen sulfide (H₂S)-producing enzymes, mediating the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) during pregnancy, thereby offering novel molecular targets for early diagnosis and intervention of related disorders. By establishing a MAFLD pregnant mouse model, we comprehensively examined the regulatory effects of 4-HNE on placental function and its interaction with the H₂S system. We found that MAFLD pregnant mice exhibited significant glucose metabolic disorders, hepatic steatosis, and placental damage. Mechanistically, 4-HNE disrupts H₂S biosynthesis, thereby impairing its inhibitory effect on the inflammasome pathway while simultaneously activating inflammatory cascades. This synergistic action exacerbates placental pathological damage, manifesting as abnormal vascular function and impaired materno-fetal exchange. Notably, exogenous H₂S intervention partially reversed 4-HNE-induced toxicity, suggesting the therapeutic potential of targeting this pathway. These findings demonstrate the pivotal role of the “4-HNE–H₂S–NLRP3” regulatory axis in MAFLD-associated placental injury, providing novel mechanistic insights and potential therapeutic targets for pregnancy complications.
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PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2023
·
IF 5.1
Xinyu Qian,Lin Zhu,Mengzhen Xu,Haoli Liu,Xinyan Yu,Qiuyue Shao,Jing Qin
Small cell lung cancer (SCLC) is a subtype of lung cancer with a very poor overall survival rate due to its extremely high proliferation and metastasis predilection. Shikonin is an active ingredient extracted from the roots of Lithospermum erythrorhizon, and exerts multiple anti-tumor functions in many cancers. In the present study, the role and underlying mechanism of shikonin in SCLC were investigated for the first time. We found that shikonin effectively suppressed cell proliferation , apoptosis , migration, invasion, and colony formation and slightly induced apoptosis in SCLC cells. Further experiment indicated the shikonin could also induced ferroptosis in SCLC cells. Shikonin treatment effectively suppressed the activation of ERK, the expression of ferroptosis inhibitor GPX4 , and elevated the level of 4-HNE, a biomarker of ferroptosis. Both total ROS and lipid ROS were increased, while the GSH levels were decreased in SCLC cells after shikonin treatment. More importantly, our data identified that the function of shikonin was dependent on the up-regulation of ATF3 by performing rescue experiments using shRNA to silence the expression of ATF3, especially in the total and lipid ROS accumulaiton. Xenograft model was established using SBC-2 cells, and the results revealed that shikonin also significantly inhibited tumor growth by inducing ferroptosis. Finally, our data further confirmed that shikonin activated ATF3 transcription by impairing the recruitment of HDAC1 mediated by c-myc on the ATF3 promoter , and subsequently elevating of histone acetylation . Our data documented that shikonin suppressed SCLC by inducing ferroptosis in a ATF3-dependent manner. Shikonin upregulated the expression of ATF3 expression via promoting the histone acetylation by inhibiting c-myc-mediated HDAC1 binding on ATF3 promoter.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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药理学
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Fang Wang,Xuchen Wang,Wenlong Xiao,Mengyao Zhu,Kai Huang,Nani Wang
Toxic reactive aldehyde, 4-hydroxy-2-nonenal (4-HNE), is an advanced lipid peroxidation product, that contributes to various oxidative stress-related diseases. However, the quantitation of 4-HNE in biological samples remains a challenge. Here, a localized surface plasmon resonance (LSPR) biosensor is modified with the antibody targeting 4-HNE. The method is induced for directly quantifying 4-HNE in serum samples. The proposed LSPR method shows a short analysis time (10 min) and good sensitivity toward 4-HNE, with a detection limit of 0.15 nmol/L. The linearization of the signal allows the detection of 4-HNE in the range of 1.00–20.00 nmol/L. The LSPR method archives an interday precision of 3.96 %. The high selectivity of the LSPR method for 4-HNE is verified by two analogs, namely, 10-undecenal and 4-heptenal. This LSPR method is used for the direct detection of 4-HNE in mouse serum. Recovery ranges from 96.09 % to 100.37 % and precision ranges from 1.65 % to 3.10 %. An agreement between the results obtained using the LSPR method and Western blotting demonstrates that the developed LSPR method can be applied to measure the lipid peroxidation marker 4-HNE in biological samples. This work represents the first LSPR method for quantifying 4-HNE in serum, where samples are analyzed directly.
研究领域:
生物化学
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医学诊断
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传感技术
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高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Jiajun Chen,Nan Zhu,Feixuan Wang
A simultaneous detection of MDA/4-HHE/4-HNE method is developed by UHPLC-QqQ-MS/MS. • Optimized derivatization and purification reduced interference from lipid impurities. • This validated method showed high sensitivity/precision with low LOD/LOQ. • Micrograms per kilogram level sensitivity capably monitors lipid peroxidation in oily food. A novel and sensitive method using ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) was developed for the simultaneous determination of three lipid oxidation markers: malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE), and 4-hydroxy-2-nonenal (4-HNE) in edible oils and nuts. Optimization of 2,4-dinitrophenylhydrazine (DNPH) derivatization and solid-phase extraction (SPE), combined with isotope compensation to ensure high analytical performance: linearity ( R ≥ 0.9990), precision (RSD ≤ 18.75%), accuracy (SD ≤ 19.24%), recovery (80.34–119.78%). Limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.25 to 0.50 μg/kg and 0.50–2.50 μg/kg, respectively. This validated method was further applied to monitor lipid peroxidation levels, revealed that thermal processing significantly increases MDA/4-HHE/4-HNE contents, which reached 7.80 mg/kg from 26.50 μg/kg in oils and 0.98 mg/kg from 8.27 μg/kg in nuts. Notably, the accumulation of MDA and 4-HHE in edible oils was approximately tenfold higher than in nuts. A novel and sensitive method using UHPLC-QqQ-MS/MS was developed for the simultaneous determination of three lipid oxidation markers: MDA, 4-HHE and 4-HNE in edible oils and nuts. Optimization of DNPH derivatization and SPE, combined with isotope compensation to ensure high analytical performance. Download: Download high-res image (119KB) Download: Download full-size image
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Andishe Dashti,Amir Reza Karamibonari,Mohammad Reza Farahpour,Zohreh Ghazi Tabatabaei
The fabrication of a safe antibacterial wound dressing lack of antibiotics is essential for the wound healing process. Hydrogels with appropriate mechanical properties containing antibacterial agents are good candidates for this purpose. This novel study was conducted to evaluate the effectiveness of hydrogels prepared from eugenol encapsulated into phytosome and chitosomes (HG-Phyt/Chit@Eu) on the wound healing process of infected wounds. The physicochemical properties, toxicity, eugenol release and antibacterial activities of formulations were assessed under in vitro condition. The HG-Eu, HG-Phyt@Eu, and HG-Phyt/Chit@Eu were formulated into hydrogel form and administrated for the treatment of infected wounds. The physicochemical results confirmed successful synthesis of formulations. The results showed that formulations were safe and exhibited antibacterial activity against positive and/or negative-Gram bacteria. The addition of phytosome and chitosomes reduced the rapid release of Eu. Topical administration of hydrogels significantly accelerated the wound healing process by decreasing total bacterial count and the expressions of COX-2, 4-HNE, NF-κB, Nrf2, iNOS-positive cell and increasing the expression of COL-1A positive staining compared with control mice. In conclusion, this preliminary study showed that HG-Phyt/Chit@Eu could compete with mupirocin and can be used for the treatment of infected wounds.
研究领域:
药剂学
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生物医学工程
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伤口愈合
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药学科学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Hanhan Xie,Ji Yang,Tong Liu,Xinyue Zhang,Shan Zuo,Yingjie Gao,Xi Kuang,Tao Zhang
Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.
研究领域:
胃肠病学
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药理学
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分子生物学
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免疫学
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PubMed
高影响因子
EXPERIMENTAL ANIMALS
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2024
·
IF 2.2
Jingzhi WANG,Zhongyu HUANG,Yiwen LI,Qian LI,Xi LI,Li CHEN
At present, there lacks a definitive pharmaceutical intervention or therapeutic approach for diabetes-associated cognitive impairment. Herein, we delved into the impact of electroacupuncture on cognitive function in high-fat diet/streptozocin (HFD/STZ)-induced T2DM mice and underlying mechanisms. Hippocampal insulin resistance was determined by western blot analysis. Cognitive function was evaluated by Morris water maze test. The morphology of the hippocampal neurons was observed through hematoxylin & eosin staining and Nissl staining. Synaptic plasticity was assessed by western blot analysis. Immunofluorescence, immunohistochemistry, western blot and real-time PCR were employed to detect the levels of ferroptosis markers, autophagy markers, and netrin-1. Electroacupuncture treatment exhibited ameliorative outcomes on spatial learning, memory function, hippocampal insulin resistance, neuronal damage, and synaptic plasticity in T2DM mice. Furthermore, it effectively suppressed neuronal ferroptosis within the hippocampus by upregulating GPX4 and SLC7A11 expression, and reducing 4-HNE expression. Meanwhile, electroacupuncture intervention increased the levels of Beclin1 and LC3II/LC3I, as well as decreased the levels of p62 and phosphorylated-mTOR in the hippocampus of T2DM mice, suggesting that electroacupuncture facilitated autophagy activation by inhibiting mTOR activity. 3-MA-mediated autophagy inhibition undermined the beneficial effects of electroacupuncture on neuronal ferroptosis and cognitive deficits in T2DM mice. Additionally, the beneficial effects of electroacupuncture on autophagy and ferroptosis was achieved by upregulation of netrin-1 in the hippocampus. Our study revealed that that electroacupuncture therapy inhibited neuronal ferroptosis via the activation of autophagy, thereby ameliorating cognitive deficits in T2DM mice.
研究领域:
神经科学
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糖尿病学
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认知科学
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药理学
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分子生物学
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2018
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IF 4.358
Chen Wang,Jing An,Yingchen Bai,Hui Li,Haibo Chen,Dong Ou,Yongdi Liu
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited. In the current study, Caenorhabditis elegans ( C. elegans , L1 larvae) were exposed to TDCPP at environmentally relevant concentrations (control, 0.1, 1, 100 and 1000 μg L −1 ) for 72 h to explore any association between TDCPP and the aging process. Some of the degenerative age-related indicators were observed, including locomotion behaviors and lifespan. As crucial biomarkers of aging, the accumulation of lipofuscin, and lipid peroxidation (LPO) products exemplified by 4-hydroxynon-2-enal (4-HNE) were detected. This product forms as a result of oxidative stress , as confirmed by an N-acetyl-L-cysteine (NAC) pharmacological assay. Moreover, a significant increase in reactive oxide species (ROS) production in a dose-dependent manner using a fluorescent probe was observed. For the underlying molecular mechanism of the above aging phenotypes, significantly upregulated transcription of genes related to antioxidant systems, especially a subset of glutathione S-transferase ( gst-5, gst-6, gst-9, gst-10, gst-19, gst-24, gst-26, gst-29, gst-33, and gst-38 ), was found by RNA-Seq and further confirmed by RT-qPCR. The elevated glutathione S-transferase (GST) was attributed to the significant increase in 4-HNE because mutations in gst-5 and gst-24 inhibited the conjugation of GSTs with 4-HNE. Therefore, GST play an indispensable role in the detoxification process of TDCPP exposure and further confirmed LPO accumulation at the molecular mechanism level. In conclusion, TDCPP accelerated the aging process induced by the LPO products, 4-HNE, response to reactive oxidative species in C. elegans .
研究领域:
毒理学
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环境科学
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分子生物学
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衰老研究
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Chaojuan Wen,Xinyue Yu,Jingya Zhu,Jingshu Zeng,Xielan Kuang,Youao Zhang,Shiyu Tang,Qingjiong Zhang,Jianhua Yan,Huangxuan Shen
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPARα-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPARα and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease.
研究领域:
眼科学
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药理学
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细胞生物学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 5
·e1229
·
IF 3.1
Meng Zhang,Deyuan Zhi,Pei Liu,Yajun Wang,Meili Duan
Background Dioscin has many pharmacological effects; however, its role in sepsis-induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model. Methods The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4-Hydroxy-2-nonenal (4-HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B-cell lymphoma-2 (Bcl-2), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated-p65 (p-p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real-time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and dihydroethidium staining assays. Results Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4-HNE level in SIC rats. Dioscin reversed LPS-induced reduction on SOD, CAT, GSH, and Bcl-2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p-p65/p65 value in LPS-induced H9c2 cells. Conclusion Protective effects of Dioscin against LPS-induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.
研究领域:
药理学
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心脏病学
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免疫学
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细胞生物学
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PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2017
·
IF 3.165
Xinyi Zhao,Rui Li,Ying Liu,Xuehong Zhang,Min Zhang,Zhi Zeng,Limin Wu,Xuelin Gao,Tian Lan,Yiqing Wang
Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Polydatin, a glucoside of resveratrol , has been shown to possess anti-oxidative bioactivity. It has been demonstrated that resveratrol has many therapeutic effects on liver disorders including liver fibrosis. Recent study showed that polydatin prevented acute liver injury after carbon tetrachloride (CCl 4 ) induction. However, the protective effects of polydatin on chronic liver injury and fibrosis has not been understood. Thus, we aimed to determine the roles of polydatin in chronic liver injury and fibrosis. Mice were induced by CCl 4 for 6 weeks to develop chronic liver injury and fibrosis. Mice were treated with polydatin for 3 and 6 weeks, respectively. After 6 week injection of CCl 4 , the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly increased. The hepatic expression of α-SMA, collagen deposition and macrophage filtration were also increased. Furthermore, hepatic 4-HNE production and NOX4 expression were also increased in CCl 4 -induced mice. In contrast, polydatin ameliorated impaired liver function and histology. Moreover, polydatin attenuated liver fibrosis and inflammation in mice induced by CCl 4 . Additionally, polydatin suppressed hepatic 4-HNE production and NOX4 expression. In conclusion, polydatin ameliorate chronic liver injury and fibrosis through inhibition of oxidative stress and inflammation.
研究领域:
药理学
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肝病学
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毒理学
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DOI
PubMed
高影响因子
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