Aging-US
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2018
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IF 5.179
Junyu Nie,Peng Xiao,Xuefang Wang,Xiaogan Yang,Huiyan Xu,Kehuan Lu,Shengsheng Lu,Xingwei Liang
Prolonged culture of metaphase II oocytes is an in vitro aging process that compromises oocyte quality. We tested whether melatonin preserves epigenetic modifications in oocytes after prolonged culture. The porcine oocytes were maturated in vitro for 44 h, and then metaphase II oocytes were continuously cultured in medium supplemented with or without melatonin for 24 h. We found that the parthenogenetic blastocyst formation rate of prolonged-culture oocytes was lower than in fresh oocytes. We further observed that methylation at H3K4me2 and H3K27me2 of oocytes enhanced after prolonged culture. However, 5mc fluorescence intensity was lower in prolonged-culture oocytes than in fresh oocytes. Moreover, the promoter of the imprinted gene NNAT exhibited a higher level of DNA methylation in prolonged-culture oocytes than in fresh oocytes, which was associated with a reduced expression level and glucose uptake capability. Conversely, melatonin improved blastocyst formation rate and preserved histone and DNA methylation modifications, as well as NNAT function in the oocytes after prolonged culture. Notably, DNA methyltransferase inhibitor 5-aza significantly attenuated the protective role of melatonin on genomic DNA methylation. In summary, our results revealed that epigenetic modifications are disrupted in oocytes after prolonged culture, but the changes are reversed by melatonin.
研究领域:
生殖生物学
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表观遗传学
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分子生物学
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DOI
PubMed
高影响因子
Cell Reports
·
2024
·
IF 7.5
Weigang Wang,Na Yang,Liangliang Wang,Yuanxiang Zhu,Xiao Chu,Weijie Xu,Yawei Li,Yihai Xu,Lina Gao,Beibei Zhang,Guoqiang Zhang,Qinmiao Sun,Weihong Wang,Qiang Wang,Wenxin Zhang,Dahua Chen
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
研究领域:
发育生物学
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分子遗传学
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颅面生物学
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DOI
PubMed
高影响因子
Journal of Instrumentation
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2021
·Vol. 16
·期 09
·P09021
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IF 1.415
R. Zhang,Y. Jia
DNA methylation sensor is an emerging demand of modern medical for laboratory, though lots of efforts have been contributed in this discipline, the easy-to-operate and efficient sensing terminal is still in deficiency. In this work, a total solution processable printing technology is proposed to fabricate the DNA methylation sensor, which is based on the liquid gate graphene field effect transistor (Lg-GFET). Meanwhile, the graphene ink (G-ink) was prepared by using the modified liquid-exfoliation method, to facilitate printing production. Then, five kinds of tested single strand DNA (ssDNA) which have 0 to 4 5-methylcytosine (5mC) sites were covalently anchored on the graphene channel. X-ray photoelectron spectroscopy (XPS) was conducted to demonstrate the analyte ssDNA was successfully fixed. Thirdly, the 5mC sites were identified by their antibody of 5mC (5mCab) and transduced as the changed current between the source and drain electrodes (Ids). It is found the proposed sensor has good linear sensitivity (about -1.68% for per 5mC) to the amount of 5mC sites on the tested ssDNAs with Pearson correlation coefficient -0.98 and excellent anti-interference to unmethylated ssDNAs. Besides, the cost is estimated to be about $ 1.5 for each of the proposed DNA methylation sensor. Conclusively, the proposed low-cost component may be an efficient candidate for promoting the instant DNA methylation determination.
研究领域:
生物传感器
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纳米技术
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分子生物学
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医学诊断
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DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Fang Dan,Xu Tianqi,Li Fulei,Sun Yue,Sun Jingyi,Yin Yanqing,Zhang Haijie,Wang Zhiqiang,Liu Yuan
Tigecycline is a last-resort antibiotic to treat complicated infections caused by multidrug-resistant pathogens, while the emergence of plasmid-mediated tet (X) family severely compromises its clinical efficacy. Novel antimicrobial strategies not limited to new antibiotics in pharmaceutical pipeline are urgently needed. Herein, we reveal the metabolic disparities between tet (X)-negative and -positive E. coli , including distinct energy demand patterns under tigecycline exposure. In particular, the cysteine and methionine metabolism pathway is remarkably downregulated in tet (X)-positive bacteria. More importantly, we find that the addition of exogenous L-methionine (Met) effectively resensitizes tet (X)-positive pathogens to tigecycline. Our mechanistic analysis demonstrates that exogenous Met promotes intracellular tigecycline accumulation by upregulating bacterial proton motive force. Moreover, Met accelerates the conversion to S-adenosyl-L-methionine, an essential methyl donor, thereby enhancing 5mC methylation modification in the promoter region of tet (X4) gene and reducing its expression. Consistently, the potentiation of Met to tigecycline is abolished in tet (X4)-carrying E. coli Δ dcm but restored in dcm -complementary bacteria, which encodes DNA-cytosine methyltransferase. In multiple animal models of infection, Met markedly potentiates the effectiveness of tigecycline against pathogenic E. coli and K. pneumoniae . Overall, this work highlights the therapeutic potential of Met in overcoming plasmid-mediated high-level tigecycline resistance, and provides a new paradigm to enhance antibiotic efficacy by harnessing cellular metabolic networks as well as epigenetic modifications.
研究领域:
微生物学
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药理学
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分子生物学
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传染病学
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代谢工程
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2023
·
IF 19
Yangcenzi Xie,Mingyang Chen,Xinyu Liu,Xiaoming Su,Ming Li
Epigenetic DNA methylations are early and frequently observed events in a diversity of diseases such as cancer. Despite the considerable clinical values for cancer liquid biopsy, quantitative analysis of DNA methylations remains a major challenge due to the lack of rapid, sensitive detection techniques. Here, an artificial intelligence-assisted label-free surface-enhanced Raman spectroscopy (SERS) (iMeSERS) biosensor is reported for simultaneous quantification of C 5 -methylcytosine ( 5m C) level and methylation ratio in DNA samples. This method utilizes the plasmonic Pickering emulsions as the biosensing platform for label-free SERS detection, formed upon the addition of a sub-microliter DNA sample to the hydrophobic Au nanostar-containing n -decane. Distinct spectral signatures of monophosphates of canonical deoxyribonucleotides (dNMPs) and the common methylation modification 5-methyl-2′-deoxycytidine (d 5m CMP) are identified and distinguished by the iMeSERS biosensor. The deep learning algorithms trained with SERS signatures of dNMPs and d 5m CMP are then applied to the quantitative analysis of global DNA methylation. The exceptional capability of the deep learning-driven approach is demonstrated for simultaneous quantification of the methylation ratio and level using a sub-microliter volume of DNA samples. This work shows the power of label-free SERS techniques combined with deep learning algorithms for quantitative analysis of epigenetic DNA modifications with great promises for clinical diagnosis.
研究领域:
生物医学工程
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分析化学
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分子生物学
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人工智能
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癌症研究
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DOI
高影响因子
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