Molecular Therapy-Nucleic Acids
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2020
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IF 7.032
Yanni Ge,Ran Zhang,Yuqing Feng,Huiling Li
Recent studies reported that DNA methylation was involved in retinal cell death. Methyl-CpG binding domain protein 2 (Mbd2) is one of the DNA methylation readers. Its role and mechanism of regulation remain unclear. The ischemia/reperfusion (I/R) model in mice primary culture retinal ganglion cells (RGCs) and Mbd2 knockout (Mbd2-KO) mice was used in the current study. We demonstrated that Mbd2 mediates RGC apoptosis caused by I/R injury. Mechanistically, the data suggested that Mbd2 upregulated Mbd2-associated long noncoding RNA 1 (Mbd2-AL1) via demethylation of its promoter. Furthermore, Mbd2-AL1 sponged microRNA (miR)-188-3p, thus preventing tumor necrosis factor (TNF) receptor-associated factor 3 (Traf3) downregulation and inducing RGC apoptosis. This was further demonstrated by the fact that inhibition of miR-188-3p diminished the anti-apoptosis role of Mbd2-AL1 small interfering RNA (siRNA). Finally, it showed that the apoptosis of retinal cells was attenuated, and the visual function was preserved in Mbd2-KO mice, which were associated with the Mbd2-AL1/miR-188-3p/Traf3 axis. Our present study revealed the role of Mbd2 in RGC apoptosis, which may provide a novel therapeutic strategy for retinal ischemic diseases.
研究领域:
神经科学
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分子生物学
·
眼科学
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
LuLu Cao,Xianqiang Gao,Yunlei Zhou,Shugang Zhang,Miao Zhang,Huanshun Yin
The advanced structural design of semiconductor photoactive materials is the core element to improve the performance of photoelectrochemical (PEC) biosensors. By constructing a BiOIO 3 @Bi 4 O 5 Br 2 Z-Scheme heterojunction with abundant oxygen vacancies to significantly improve the photoelectric conversion efficiency, a sensitively PEC biosensor for MBD2 detection was designed by combining DNA isothermal cycle double amplification technology. Specifically, the chitosan-modified BiOIO 3 @Bi 4 O 5 Br 2 was modified on the surface of ITO electrode. Methylene blue (MB)-DNA was immobilized on due to the covalent reaction of its carboxyl group with the amino group of chitosan, and the excess amino group was blocked with acetaldehyde. In the absence of MBD2, the cleavage activity of HpaII is inhibited due to the retention of cytosine methylation. which triggers ISDPR and large amounts of single-stranded DNA complementary to MB-DNA was produced. After MB-DNA hybridization, Exo III was triggered to assist the MB-DNA hydrolysis cycle, resulting in the drop of MB, causing a decrease in the photoelectric signal. Conversely, in the presence of MBD2, it removed cytosine methylation, triggering HpaII hydrolysis and inhibiting subsequent reactions, so that the MB connected to the electrode is retained and the photoelectric signal is enhanced. The sensor had a detection range from 0.07 to 500 ng/mL with a detection limit of 0.018 ng/mL (3σ). The study also explores the effects of environmental pollutants on MBD2 activity and validated with molecular docking models, offering insights into epigenetic regulation and environmental health assessments. This work underscores the potential of advanced photoactive materials and heterojunction designs in biosensor applications.
研究领域:
生物传感
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材料科学
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分子生物学
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高影响因子
Cell Death & Disease
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2025
·Vol. 16
·期 1
·1-16
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IF 9.6
Jing Yukai,Zhang Yunfei,Wang Xiaocui,Wang Yufen,Hu Ying,Wen Bin,Dai Xin,Duan Xuemei,Li Haonan,Dong Shumin,Yan Ze,Fan Yufeng,Wang Cong-yi,Liu Xiansheng,Zhang Ruiping
Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the overproduction of autoantibodies and type I interferon, which damages its own tissues, causing multiple organ damage. B cells are thought to play a major role in the pathogenesis of SLE. As a DNA methylation reader, Methyl-CpG-binding domain protein 2 (MBD2) has been extensively studied in the contexts of innate immunity, adaptive immunity, and autoimmune diseases. However, its specific role in B cells and SLE remains unexamined. Herein, we found that MBD2 was highly expressed in B cells of SLE patients and positively correlated with disease activity. Knockout of MBD2 in B cells disturbed B-cell differentiation, dampened B-cell activation, B-cell receptor (BCR) signaling, and T-cell-dependent humoral immune responses in mice. What’s more, MBD2 deficiency effectively attenuated lupus-like symptoms, reduced the germinal center responses, and decreased anti-dsDNA antibodies in lupus model mice. Mechanistically, MBD2 selectively bound to the methylated CpG of Lef-1 induced by IFN-α, inhibiting the transcription and expression of Lef-1 , which repressed Pten transcription and expression, thereby promoting PI3K-Akt-mTOR signaling. This study first demonstrated the role of MBD2 in the pathogenesis of SLE and provided a new target for SLE.
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Small
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2023
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IF 13.3
LuLu Cao,Yunlei Zhou,Lanlan Gao,Huanshun Yin,Miao Zhang,Haowei Zhang,Peng Ju,Kunpeng Dou,Shiyun Ai
Oxygen vacancy defects (OVs) are one of the main strategies for nanomaterials modification to improve the photoactivity, but current methods for fabricating OVs are usually complicated and harsh. It is important to develop simple, rapid, safe, and mild methods to fabricate OVs. By studying the effects of different weak reducing agents, the concentration of the reducing agent and the reaction time on fabrication of OVs, it is found that L -ascorbic acid (AA) gently and rapidly induces the increase of OVs in Bi 4 O 5 Br 2 at room temperature. The increased OVs not only improve the adsorption of visible light, but also enhance the photocurrent response. Based on this, the preparation of OVs in Bi 4 O 5 Br 2 is employed to the development of a photoelectrochemical biosensor for the detection of DNA demethylase of methyl-CpG binding domain protein 2 (MBD2). The biosensor shows a wide linear range of 0.1–400 ng mL −1 and a detection limit as low as 0.03 ng mL −1 (3σ). In addition, the effect of plasticizers on MBD2 activity is evaluated using this sensor. This work not only provides a novel method to prepare OVs in bismuth rich materials, but also explores a new novel evaluation tool for studying the ecotoxicological effects of contaminants.
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高影响因子
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