Advanced Science
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2025
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IF 14.1
Qian Yuan,Yuting Zhu,Ben Tang,Yaru Xie,Mingcun Hu,Hua Su,Youhua Liu,Chun Zhang
Cellular senescence is a hallmark of aging and the accumulation of senescent cells (SnCs) accelerates the aging process, contributing to aging-related organ disorders. The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, this work demonstrates that PRDM16, a member of the PRDM protein family, decreases significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging-related organ injury. Furthermore, tubular-specific Prdm16 deletion aggravates irradiation-induced kidney aging and aging-related kidney diseases in irradiated mice subjected to ischemia-reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulates the transcription of glutathione S-transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reverses PRDM16 deficiency-induced cellular senescence and kidney aging. Collectively, these results provide a potential target for the investigation of anti-aging therapies.
研究领域:
分子生物学
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老年学
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肾脏病学
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氧化应激
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遗传学
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转化医学
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信号转导
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产品关联
DOI
PubMed
高影响因子
SCIENTIA HORTICULTURAE
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2011
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IF 1.045
Hui-Cong Wang,Zhi-Qun Hu,Yan Wang,Hou-Bin Chen,Xu-Ming Huang
The pericarps of 10 litchi cultivars from two production seasons were studied for their phenolic concentrations and composition and activities of anti-oxidation. The total phenolic concentrations in dried litchi pericarp ranged from 51 to 102 g k g −1 . Different cultivars varied considerably in phenolic concentration and composition. Cultivars ‘Nuomici’ exhibited significantly higher concentrations of proanthocyanidins, flavonoids, phenolic acids and therefore total soluble phenolics than the other cultivars, while ‘Lanzhu’ and ‘Guiwei’ had minor values in phenolics. The extracts of litchi pericarp exhibited considerably high ferric reducing antioxidant power (FRAP) and strong activities of 1,1-diphenyl-2-picryhydrazyl (DPPH) scavenging, lipid peroxidation inhibiting, and oxidative DNA damage protection. The crude ethanol extracts of pericarp displayed significantly higher FRAP and stronger DPPH scavenging capacity than butylated hydroxylytoluene (BHT) and catechin. Among the tested cultivars, concentrations of major phenolics had significant linear correlations with FRAP and DPPH scavenging activities. These results indicated that litchi pericarp is rich in natural antioxidant phenolic compounds and different litchi cultivars differed considerably in phenolic concentration and antioxidant activities.
研究领域:
食品科学
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农业
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植物化学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Jia-Hui Dong,Chen-Yu Xue,Xin-Ying Zhong,Ying-Lin Zhou,Xin-Xiang Zhang
Oxidative DNA damage is tightly linked to the development of multiple age-related diseases. The prominent oxidation product is 8-oxo-7,8-dihydroguanine (OG), which has been proved to be an important epigenetic-like biomarker. Quantification of the locus-specific OG frequency includes quantitative and locating information, which is of great significance for exploring the functional roles of OG in disease induction and gene regulation. Herein, an ultrasensitive quantification of OG at single-base resolution was established using real-time fluorescence quantitative polymerase chain reaction as an amplification tool. Based on the coding property of Bsu DNA polymerase that incorporates adenine on the opposite site of OG and the selectivity of the ligase for perfectly matched sequences, the difference between OG and G on the sequence could be enlarged. Well-performed Taq DNA ligase was selected out, and as low as 46.2 zmol of target DNA with an OG site and an OG frequency of 5% could be detected. G contents on a specific site were also detectable based on the similar principle, thus the OG frequency of this locus could be accurately determined by a standard addition method. This strategy was successfully applied to the evaluation of locus-specific OG in both model DNA and genomic DNA from human cervical carcinoma cell lines under multiple oxidative stress, showing the potential for functional research and dynamic monitoring of critical OG sites.
研究领域:
生物化学
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分子生物学
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基因组学
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疾病研究
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Yemian Zhou,Yun Liu,Tong Wang,Han Li,Jing He,An Xu
Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (A L ) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs.
研究领域:
环境科学
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毒理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
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2018
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IF 3.432
Wenjing Dong,Bingwei Yang,Yawen Wang,Jia Yuan,Yunqi Fan,Erqun Song,Yang Song
Polybrominated diphenyl ethers (PBDEs) are emerging organic environmental pollutants, which were accused of various toxic effects. Here, we studied the role of a potential PBDEs quinone metabolite, PBDEQ, on cytotoxicity, oxidative DNA damage, and the alterations of signal cascade in HeLa cells. PBDEQ exposure leads to reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) loss, lactate dehydrogenase (LDH) release, increasing terminal transferase-mediated dUTP-biotin nick end labeling (TUNEL) positive foci, and the elevation of apoptosis rate. Furthermore, we showed PBDEQ exposure result in increased DNA migration, micronucleus frequency, and the promotion of 8-OHdG and phosphorylation of histone H2AX (γ-H2AX) levels. Mechanism study indicated that PBDEQ caused poly(ADP-ribose) polymerase 1 (PARP-1) activation and apoptosis-inducing factor (AIF) nuclear translocation. All together, these results confirmed the occurrence of parthanatos-like cell death upon PBDEQ exposure.
研究领域:
毒理学
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细胞生物学
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环境科学
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分子生物学
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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）