COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·Vol. 27
·期 11
·1611-1628
·
IF 1.6
Pan Chengzhen,Zhang Chi,Lin Zonghan,Liang Zhou,Cui Yinhang,Shang Zhihao,Wei Yuanxun,Chen Feng
Background: Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. Objective: The study
aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. Methods: Differential expression analysis was conducted on disulfide-related
genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116
dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting
mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. Results: RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune
infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was
found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally
high expression of RPN1 in the femur of ovariectomized rats. Conclusion: RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.
研究领域:
医学研究
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药理学
·
分子生物学
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免疫学
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生物信息学
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DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2017
·
IF 6.392
Yingting Yu,Yi Yao,Hao Yan,Rui Wang,Zhenming Zhang,Xiaodan Sun,Lingyun Zhao,Xiang Ao,Zhen Xie,Qiong Wu
Targeted therapy for cancer is a research area of great interest, and magnetic nanoparticles (MNPs) show great potential as targeted carriers for therapeutics. One important class of cancer biomarkers is microRNAs (miRNAs), which play a significant role in tumor initiation and progression. In this study, a cascade recognition system containing multiple plasmids, including a Tet activator, a lacI repressor gene driven by the TetOn promoter, and a reporter gene repressed by the lacI repressor and influenced by multiple endogenous miRNAs, was used to recognize cells that display miRNA signals that are characteristic of cancer. For this purpose, three types of signal miRNAs with high proliferation and metastasis abilities were chosen (miR-21, miR-145, and miR-9). The response of this system to the human breast cancer MCF-7 cell line was 3.2-fold higher than that to the human breast epithelial HBL100 cell line and almost 7.5-fold higher than that to human embryonic kidney HEK293T cells. In combination with polyethyleneimine-modified MNPs, this recognition system targeted the tumor location in situ in an animal model, and an ≃42% repression of tumor growth was achieved. Our study provides a new combination of magnetic nanocarrier and gene therapy based on miRNAs that are active in vivo , which has potential for use in future cancer therapies.
研究领域:
癌症研究
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纳米技术
·
基因治疗
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2018
·Vol. 143
·期 13
·3134-3140
·
IF 3.864
Xiaotong Wei,Xiaolei Duan,Xiaoyan Zhou,Jiangling Wu,Hongbing Xu,Xun Min,Shijia Ding
Herein, a dual channel surface plasmon resonance imaging (SPRi) biosensor has been developed for the simultaneous and highly sensitive detection of multiplex miRNAs based on strand displacement amplification (SDA) and DNA-functionalized AuNP signal enhancement. In the presence of target miRNAs (miR-21 or miR-192), the miRNAs could specifically hybridize with the corresponding hairpin probes (H) and initiate the SDA, resulting in massive triggers. Subsequently, the two parts of the released triggers could hybridize with capture probes (CP) and DNA-functionalized AuNPs, assembling DNA sandwiches with great mass on the chip surface. A significantly amplified SPR signal readout was achieved. This established biosensing method was capable of simultaneously detecting multiplex miRNAs with a limit of detection down to 0.15 pM for miR-21 and 0.22 pM for miR-192. This method exhibited good specificity and acceptable reproducibility. Moreover, the developed method was applied to the determination of target miRNAs in a complex matrix. Thus, this developed SPRi biosensing method may present a potential alternative tool for miRNA detection in biomedical research and clinical diagnosis.
研究领域:
生物传感技术
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分子诊断
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分析化学
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医学检测
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Yingchao Li,Canzhao Tu,Qianshun Chen,Yingying Lin,Baoming Li,Haixia Lyu
The overexpression of microRNA-222 (miRNA-222) is closely related to many human diseases, so the development of biosensors to detect this biomarker will contribute to the diagnosis of related diseases. Here, a simple, sensitive and specific fluorescence assay for the detection of miRNA-222 was developed using red-emitting upconversion nanoparticle (UCNP) as the donor and a DNA hairpin with black hole quencher-2 (BHQ-2) as the acceptor. Li + and Tm 3+ -doped UCNP with a strong emission peak at 654 nm was obtained by changing the doped ion ratio and constructing core-shell structures. Under optimal conditions, the linear range for detecting miRNA-222 is 0.5–2.5 nM and the limit of detection is as low as 0.077 nM without any complicated amplification strategy. Finally, the proposed assay was applied for the detection of miRNA-222 in serum samples. The results obtained were similar to those of the standard method, and the spiked recoveries were in the range of 97.62%–102.14 %, suggesting that the proposed method has practical value in a complex biological sample matrix.
研究领域:
生物医学
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分子诊断
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纳米技术
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Yingao Yang,Zixuan Zhou,Yifen Guo,Ruipeng Chen,Daoming Tian,Shuyue Ren,Huanying Zhou,Zhixian Gao
Background DNA tweezers, classified as DNA nanomachines, have gained prominence as multifunctional biosensors due to their advantages, including a straightforward structure, response mechanism, and high programmability. While the DNA tweezers demonstrate simultaneous, rapid, and stable responses to different targets, their detection sensitivity requires enhancement. Some small molecules , such as mycotoxins , often require more sensitive detection due to their extremely high toxicity. Therefore, more effective signal amplification strategies are needed to further enhance the sensitivity of DNA tweezers in biosensing. Results We designed programmable DNA tweezers that detect small-molecule mycotoxins and miRNAs through simple sequence substitution. While the DNA tweezers demonstrate simultaneous, rapid, and stable responses to different targets, their detection sensitivity requires enhancement. We introduced the Strand Displacement Amplification (SDA) technique to address this limitation, proposing a strategy of novel programmable DNA tweezers-SDA ultrasensitive signal amplification fluorescence sensing . We specifically investigate the effectiveness of this approach concerning signal amplification for two critical mycotoxins: aflatoxin B1 (AFB1) and zearalenone (ZEN). Results indicate that the detection ranges of AFB1 and ZEN via this strategy were 1–10,000 pg mL −1 and 10–100,000 pg mL −1 , respectively, with corresponding detection limits of 0.933 pg mL −1 and 1.07 pg mL −1 . Compared with the DNA tweezers direct detection method for mycotoxins, the newly constructed programmable DNA tweezers-SDA fluorescence sensing strategy achieved a remarkable 10 4 -fold increase in the detection sensitivity for AFB1 and ZEN. Significance The constructed programmable DNA tweezers-SDA ultrasensitive signal-amplified fluorescence sensing strategy exhibits excellent detection performance for mycotoxins. The superb versatility of this strategy allows the developed method to be easily used for detecting other analytes by simply replacing the aptamer and cDNA, which has incredible potential in various fields such as food safety screening, clinical diagnostics, and environmental analysis .
研究领域:
生物传感器
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纳米技术
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分析化学
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食品安全
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环境分析
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临床诊断
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Yun Ying Cheng,Yi Fen Xie,Chun Mei Li,Yuan Fang Li,Cheng Zhi Huang
Förster resonance energy transfer (FRET) by using fluorescent carbon dots (CDs) as energy donors shows potential for biosensing and bioimaging. However, it remains underused and underestimated for CDs as a building block for FRET owing to the low efficiency and complex operation originating from the surface modification of CDs. To overcome these limitations, herein we develop a novel FRET soft nanoball (fretSNB) in which thousands of green CDs and black hole quencher 2 (BHQ-2) dyes are loaded, and FRET occurs from CDs to BHQ-2 dyes with the consequence of effective fluorescence quenching. These fretSNBs can be ruptured in the presence of phospholipase A2 (PLA2) released in a process of duplex-specific nuclease (DSN)-assisted target recycling amplification (TRA), making the fluorescence of CDs recovered. Thus, a dual amplification strategy is successfully developed for amplified detection of microribonucleic acids (miRNAs) in the concentration range 0.025–10 nM with a limit of detection (3σ) reaching 16.5 pM which is about 515 times lower than without fretSNBs. In addition, the developed strategy exhibits high selectivity for discrimination of a single nucleotide difference and capability to detect miRNAs extracted from cells, suggesting excellent potential in biomedical analysis and clinical diagnosis.
研究领域:
生物化学
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分子生物学
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分析化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Jiwei Wang,Jingjing Fu,Han Chen,Ali Wang,Yuting Ma,Hanrong Yan,Yuting Li,Dehong Yu,Fenglei Gao,Shibao Li
Accurate quantitative, in situ and temporal tracking imaging of tumor-associated miRNAs in living cells could provide a basis for cancer diagnosis and prognosis. In this strategy, a surface-enhanced Raman scattering (SERS)-fluorescence (FL) dual-spectral sensor (DSS) was constructed based on the nanoscale photophysical properties of AuNPs , mediated by functionalized DNA , to achieve rapid imaging of FL and accurate SERS quantification of intracellular miRNAs. The dual-spectrum sensor in the strategy is highly sensitive, specific and reproducibly stable. The LOD values of the dual spectra were 3.58 pM (SERS) as well as 11.8 pM (FL) with RSD values less than 2.69%. The bispectral sensor self-assembled into a trimer by the lapidation of Y-type DNA under the excitation of the target, generating a stable enhanced electric field coupling; and selected adenine located in the enhanced electric field as the reporter molecule, simplifying the labeling process and variables of the Raman reporter molecule, distinguishing it from other traditional methods. This strategy successfully achieved accurate tracking and quantification of miR-21 in cancer cells and showed good stability in the cells. The reported probes are potential tools for reliable monitoring of biomolecular dynamics in living cells.
研究领域:
纳米技术
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生物医学工程
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2022
·
IF 5.273
Jingli Chen,Chang Liu,Mu Xu,Jiaxi Zhu,Zhongyuan Xia
Chronic stress is associated with impairment of synapse plasticity in hippocampus and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is believed to take responsibility for dendritic atrophy and reduction of spine number induced by chronic stress in hippocampus. But little is known about the molecular mechanisms underlying CORT induced abnormal synapse plasticity and cognitive dysfunction. Drebrin is an F-actin binding protein that modulates memory formation and maintenance by controlling the genesis and morphology of dendritic spines . In addition, miRNAs have been reported to participate in the negative regulation of protein-coding genes. In this study, five miRNAs capable of targeting Drebrin were selected by searching miRNA databases. One of these miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of mice with chronic restraint stress (CRS). Luciferase reporter assay and Fluorescence in situ hybridization (FISH) were employed to identify the interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p expression in vivo using an antagomir or in vitro using an inhibitor increased Drebrin expression , ameliorated the abnormal dendritic structure and upregulated the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary hippocampal neurons cultured under CORT stimulation, respectively. Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the limited synaptic transmission and synaptic plasticity in hippocampal neurons. Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in CRS mice. These in vivo and in vitro findings indicate that the upregulation of miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive impairment by targeting Drebrin.
研究领域:
神经科学
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分子生物学
·
认知科学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 7
·e0313233
·
IF 2.6
Muyao Ding,Hongyu Ma,Hui Du,Yinglong Yang,Min Yu,Cong Zhang
DEHP is the most widely used plasticizer in many products. However, growing evidence has indicated that DEHP may induce neurotoxicity. DEHP exposure affects mircoRNAs (miRNAs) expression in brain. A growing body of evidence suggests that nutrients and other bioactive food components prevent neurotoxicity through regulation of miRNA expression. Due to the increasing concern about the risks of DEHP to human health, we explored the neuroprotective effect of Omega-3 fatty acid (Omega-3FA) on subchronic DEHP-induced neurotoxicity in mice, and the potential involved miRNAs and their targets in the protective action of Omega-3FA against DEHP-induced neurotoxicity. Omega-3FA protected against the DEHP-induced impairment of learning and memory and alleviated the thinning of postsynaptic density (PSD) thickness in hippocampal synapses. We observed that there are fourteen up or down regulated miRNAs associated PSD in DEHP exposure which were normalized by Omega-3FA treatment. Protein targets in PSD of these differentially expressed miRNAs were predicted. Furthermore, the expression levels of protein mGluR5, Homer1, and NMDAR2B were carried out via Western blot, for further verifying PSD associated miRNAs’ targets are involved in neuroprotection of Omega-3FA against DEHP. These findings suggested that Omega-3FA protected DEHP-induced impairment of learning and memory as well as synaptic structure alteration in the hippocampus by regulating the expression of PSD associated miRNAs and their targets. Thus, Omega-3FA should be included in diet to prevent or suppress neurotoxicity caused by continuous exposure to DEHP.
研究领域:
神经科学
·
毒理学
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营养学
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分子生物学
·
药理学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Na Deng,Ziqian He,Ruixue Guo,Bisheng Zheng,Tong Li,Rui Hai Liu
The mechanisms of highland barley whole grain (BWG) with rich phenolics on obese db/db mice were investigated in this study. Oral consumption of BWG reduced food intake, body weight, organ/body weight indexes of liver and fat, levels of serum and hepatic lipids, liver injury, and oxidative stress. Furthermore, BWG recovered the disorder of cecal microbiota by augmenting the Bacteroidetes/Firmicutes ratio and Alistipes abundance and decreasing the abundances of Bacteroides and Desulfovibrionaceae to modulate lipid metabolism-related genes. BWG inhibited fatty acid biosynthesis via upregulating the phosphorylation of AMP-activated protein kinase α, while downregulating sterol regulatory element binding protein-1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 levels. BWG also significantly downregulated miRNA-122, miRNA-33, miRNA-34a, and miRNA-206 levels. Accordingly, BWG exhibited hypolipidemic potential through modulating cecal microbiota, AMPK/SREBP-1c/FAS pathway, and related miRNAs, triggering the alleviation of dyslipidemia. These findings suggested BWG as an effective candidate to ameliorate the symptoms of hyperlipidemia.
研究领域:
营养学
·
微生物学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Xiaoyu Cai,Huimin Zhang,Xiufeng Yu,Wei Wang
MicroRNAs (miRNAs) are considered as the potential biomarkers for many cancers. To determine miRNAs in cancer cells is significant for realizing these diseases. In this work, a microfluidic paper-based laser-induced fluorescence sensor based on duplex-specific nuclease (DSN) amplification was developed and applied to selectively and sensitively determine miRNAs in cancer cells. An interface for laser-induced fluorescence detection was firstly applied to perform the sample detection on the paper-based chip. Under the optimal conditions, DSN (3 μL 0.10 U) and Taqman probes (2 μL 2.5 × 10 −7 M) were preserved on the circles (Diameter 4 mm) of the folded paper chip. When miRNA solution was added, the mixed solution could trigger fluorescence signal amplification by cyclically digesting hybrids of miRNAs and Taqman probes by DSN. The whole determination, including sample heating process, could be accomplished within 40 min. The detection limits for miRNA-21 and miRNA-31 were 0.20 and 0.50 fM respectively, corresponding to only 1.0 and 1.5 zmol consumption of miRNAs. The testing of mismatched miRNAs showed that the method had good specificity. Finally, the method was applied to determine miRNA-21 and miRNA-31 in lysates of cancer cells of A549 and HeLa, and hepatocyte LO2. MiRNA-21 and miRNA-31 could be successfully found from the two cancer cells. The concentrations for miRNA-21 and miRNA-31 were 1.74 × 10 −13 M and 6.29 × 10 −14 M in HeLa cell lysate (3.75 × 10 4 cells/mL), 3.07 × 10 −15 M and 3.28 × 10 −15 M in A549 cell lysate (8.33 × 10 6 cells/mL) respectively. The recoveries ranged from 87.30% to 111.83%, indicating the results were reliable. The developed method was effective, selective and sensitive in the determination of miRNAs in cancer cells.
研究领域:
生物医学工程
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2019
·
IF 5.256
Zhengming Cao,Fenghe Duan,Xiaoyu Huang,Yang Liu,Nan Zhou,Lei Xia,Zhihong Zhang,Miao Du
We report herein a novel multiple electrochemical aptasensor based on covalent–organic framework (COF) for sensitive and simultaneous detection of miRNA 155 and miRNA 122, by using shell-encoded gold nanoparticles (Au NPs) as signal labels ( [email protected] and Cu 2 [email protected] , respectively, NCs = nanoclusters). A new COF nanowire was synthesized via condensation polymerization of 1,3,6,8-tetra(4-carboxylphenyl)pyrene and melamine (represented by TBAPy-MA–COF–COOH) for multiple aptasensor fabrication. The nanowire was then used as a platform for anchoring single-strand DNA (ssDNA), which was hybridized with the complementary aptamer (cApt) probes of miRNA 155 and miRNA 122. [email protected] and Cu 2 [email protected] modified with cApts show separated differential pulse voltammetry (DPV) peaks at 0.08 and −0.1 V, respectively. The signal labels immobilized with cApts were released from the hybridized DNA complex and bound to their corresponding targets when contacting miRNAs. This phenomenon results in the substantial decline of the DPV peak current density of the signal labels. The developed TBAPy-MA–COF–COOH-based aptasensor has superior performance for sensing miRNA 155 and miRNA 122 simultaneously, with ultrasensitive low detection limits of 6.7 and 1.5 fM (S/N = 3), respectively, a wide linear range of 0.01–1000 pM, and high selectivity and applicability for serum samples. The proposed TBAPy-MA-based aptasensor demonstrates potential for simultaneous detection of multiple cancer biomarkers by replacing other ssDNA and aptamer strands.
研究领域:
生物化学
·
分析化学
·
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）