Cell Reports
·
2024
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IF 7.5
Zhu Li,Kexin Mao,Lin Liu,Shengyun Xu,Min Zeng,Yu Fu,Jintao Huang,Tingting Li,Guoan Gao,Zhao-Qian Teng,Qinmiao Sun,Dahua Chen,Ying Cheng
Microglia are versatile regulators in brain development and disorders. Emerging evidence links microRNA (miRNA)-mediated regulation to microglial function; however, the exact underlying mechanism remains largely unknown. Here, we uncover the enrichment of miR-137, a neuropsychiatric-disorder-associated miRNA, in the microglial nucleus, and reveal its unexpected nuclear functions in maintaining the microglial global transcriptomic state, phagocytosis, and inflammatory response. Mechanistically, microglial Mir137 deletion increases chromatin accessibility, which contains binding motifs for the microglial master transcription factor Pu.1. Through biochemical and bioinformatics analyses, we propose that miR-137 modulates Pu.1-mediated gene expression by suppressing Pu.1 binding to chromatin. Importantly, we find that increased Pu.1 binding upregulates the target gene Jdp2 (Jun dimerization protein 2) and that knockdown of Jdp2 significantly suppresses the impaired phagocytosis and pro-inflammatory response in Mir137 knockout microglia. Collectively, our study provides evidence supporting the notion that nuclear miR-137 acts as a transcriptional modulator and that this microglia-specific function is essential for maintaining normal adult brain function.
研究领域:
神经生物学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2026
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IF 7.3
Jiayi Hu,Lin Hao,Meiyu Chen,Yufan Zhang
The efficient and quantitative detection of miRNA-21 plays a critical role in early cancer diagnosis, as well as in the screening and treatment of early-stage infectious diseases. In this study, we developed an electrochemical biosensor for the detection of miRNA-21 in human serum samples. The sensor is constructed based on carboxyl-modified cobalt-doped nitrogen-doped carbon (Co-NC–COOH), a dual-output toehold-mediated strand displacement (TMSD) reaction, and gold nanoparticles (Au NPs) to achieve electrocatalytic signal amplification toward acetaminophen (AP). Co-NC–COOH possesses abundant active and catalytic sites, along with a porous surface morphology, which facilitates electron transfer and enhances the loading capacity of the capture probe (CP). In the presence of miRNA-21, the dual-output TMSD reaction is initiated, resulting in the release of a large amount of product strand (P). Subsequently, P hybridizes with the CP immobilized on the electrode surface, enabling the attachment of Au NPs to the electrode and thereby achieving significant electrochemical signal amplification. The results demonstrate that the proposed biosensor exhibits excellent analytical performance, including a wide linear detection range (0.1 fM–50 nM), an ultralow detection limit (63 aM), and satisfactory spike recovery rates (95.18%–103.59%). Moreover, the biosensor shows good stability and high specificity, providing a reliable platform for the precise quantification of miRNA-21 in human serum.
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
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IF 5.977
Lili Yang,Hao Wang,Haitao Lü,Ni Hui
A rapid, sensitive and low-fouling sensor for application to detect clinical biomarkers directly in biological media is highly desirable. Herein, we report a versatile strategy to prepare polyaniline (PANI) based conducting polymer hydrogel through the assembly of PANI and phytic acid (PA) by dynamic boronate bond. PANI/PA, a conductive hydrogel with high specific area and multiple pore structures have demonstrated excellent antifouling ability and electrochemical property. The electrochemical biosensors for microRNA can be developed by the immobilization of DNA probes onto PANI/PA interface (microRNA24 is used as a model case), and redox currents of PANI were utilized as the sensing signals to assay DNA/RNA hybridization reaction. Owing to the typical characteristics of PANI/PA hydrogel, the biosensor has shown excellent sensing performances with wide linear range (1.0 fM-1.0 pM), low sensing limit (0.34 fM) and efficient ability to detect microRNA mismatches. Given the facile processability, excellent stability and good antifouling property of the PANI/PA hydrogel, the proposed hydrogel-based biosensor may find broad applications in clinical diagnostics and biomedical devices.
研究领域:
材料科学
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生物化学
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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
Oncotarget
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2017
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IF 5.168
Hai-Ning Liu,Hao Wu,Yan-Jie Chen,Yu-Jen Tseng,Enkhnaran Bilegsaikhan,Ling Dong,Xi-Zhong Shen,Tao-Tao Liu
Background Many new diagnostic biomarkers have been developed for hepatocellular carcinoma (HCC). We selected two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and attempted to establish appropriate models. Methods We reviewed the diagnostic efficiencies of all microRNAs identified by previous diagnostic tests. Then we chose appropriate microRNAs to validate the diagnostic efficiencies, and determined the optimal combination. We included 66 patients with HCC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was performed, and we used three multivariate statistical methods to establish diagnostic models. The concentration of alpha feto-protein (AFP) was determined for comparison with the novel models. Results 82 published studies and 92 microRNAs were ultimately included in this systematic review. Seven microRNAs were selected for further validation of their diagnostic efficiencies. Among which, miR-21, miR-106b, miR-125b, miR-182 and miR-224 had a significantly different expression in HCC patients. The combination of miR-21, miR-106b and miR-224 had the highest area under the curve (AUC) at 0.950 with a sensitivity of 80.3% and a specificity of 92.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. In comparison, the AUC of the traditional biomarker, AFP, was 0.755. Conclusion MicroRNAs and metabolomics shows promising potential as new diagnostic methods due to their high diagnostic value compared with traditional biomarkers.
研究领域:
肿瘤学
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2022
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IF 6.911
Yunyun Ning,Cuiling Zhang,Chunyan Wang,Chuqing Zhou,Nana Gong,Qiang Wang,Ye Zhu
Accurate detection of microRNA (miRNA) is challenging but essential for disease diagnostics and therapeutics. To meet the high demands of miRNA analysis, we proposed a highly sensitive and specific electrochemical strategy based on duplex-specific nuclease (DSN)-assisted target recycling and DNA self-assembled FeN x C nanocatalytic network for precise quantitation of miRNA-21 as a model. FeN x C nanospherical catalyst with high peroxidase-mimicking activity was synthesized through high-temperature pyrolysis and modified with DNA. The identification of miRNA-21 by elaborately designed capture probe triggered DSN-assisted target recycling. Subsequently, self-assembled FeN x C nanocatalytic network was constructed on the sensor surface through DNA hybridization reaction, whose signal response was demonstrated to be 4.272-fold higher than the single layer of FeN x C. By virtue of such cascade signal amplification, ultrasensitive electrochemical detection of miRNA-21 was realized in a dynamic range of 0.5 fM - 1 pM with a detection limit of 0.2805 fM. Additionally, the proposed strategy exhibited high specificity for miRNA-21 and practical applicability in real sample analysis, demonstrating promising potential for the reliable miRNA analysis in disease diagnosis and therapy applications.
研究领域:
生物化学
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分子诊断
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纳米医学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2022
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IF 18.027
Wei Wei,Huiting Lu,Wenhao Dai,Xiaonan Zheng,Haifeng Dong
Multiplexed profiling of microRNAs’ subcellular expression and distribution is essential to understand their spatiotemporal function information, but it remains a crucial challenge. Herein, we report an encoding approach that leverages combinational fluorescent dye barcodes, organelle targeting elements, and an independent quantification signal, termed Multiplexed Organelles Portrait Barcodes (MOPB), for high-throughput profiling of miRNAs from organelles. The MOPB barcodes consist of heterochromatic fluorescent dye-loaded shell–core mesoporous silica nanoparticles modified with organelle targeting peptides and molecular beacon detection probes. Using mitochondria and endoplasmic reticulum as models, we encoded four Cy3/AMCA ER-MOPB and four Cy5/AMCA Mito-MOPB by varying the Cy3 and Cy5 intensity for distinguishing eight organelles’ miRNAs. Significantly, the MOPB strategy successfully and accurately profiled eight subcellular organelle miRNAs’ alterations in the drug-induced Ca2+ homeostasis breakdown. The approach should allow more widespread application of subcellular miRNAs and multiplexed subcellular protein biomarkers’ monitoring for drug discovery, cellular metabolism, signaling transduction, and gene expression regulation readout.
研究领域:
细胞生物学
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分子生物学
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纳米技术
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药物发现
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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
PEDIATRIC RESEARCH
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2023
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IF 3.6
Wang Qi,Shi Xulai,Li Ping-Ping,Gao Li,Zhou Yueyuan,Li Luyao,Ye Hao,Fu Xiaoqin,Li Peijun
Background Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. Methods miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride–pilocarpine. Results We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls ( p < 0.01), of which miR-27a-3p exhibited a very low p value ( p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased ( p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. Conclusions MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. Impact
A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children.
Plasma miR-27a-3p was one of the miRNAs with a low p value.
GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p.
miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
研究领域:
神经科学
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分子生物学
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儿科
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生物标志物研究
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
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IF 7.4
Xi Long,Tong Luo,Panpan Yuan,Yuqing Gan,Hui Liu,Zhiwei Deng,Jiacheng Ding,Zan Gong,Yanjing Yang,Shian Zhong
The ability to simply, selectively, and sensitively detect low numbers of miRNAs in clinical samples is highly valuable but remains a challenge. In this work, we present a novel miRNA detection system by using the elaborately designed hairpin switch, where the T7 primer, template, target recognize sequence, and light-up RNA aptamer template are edited and embedded in one single-stranded DNA hairpin structure. In the beginning, the hairpin switch maintained the hairpin structure 1, in which the ds promoter of T7 polymerase was disrupted, thus the transcription reaction of T7 polymerase was inhibited. After binding to the target, the hairpin switch 1 was unfolded and turned to the hairpin structure 2. This switch initiates the in vitro T7 transcription reaction, producing plenty of RNA transcripts containing RNA aptamers. Consequently, transcribed tremendous RNA aptamers lighted up the fluorophore for quantitative analysis. Compared with the existing T7 polymerase-based amplification system, this strategy exhibits several advantages, including simplicity, convenience, and high selectivity and sensitivity. The experimental results demonstrated that we could achieve the quantification of miRNA in buffer and complex biological samples.
研究领域:
分子生物学
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生物技术
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纳米技术
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临床诊断
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Zhang Xinxin,Xu Min,Cai Shuilin,Chen Bei,Lin Hetong,Liu Zhiyu
Introduction: The protective effects of astaxanthin against myocardial ischemia-reperfusion injuries are well documented, although the mechanisms are not defined.Methods: The anoxia-reoxygenation injury model was established after astaxanthin treated H9c2 cells for 24 h. Cell viability, lactate dehydrogenase, oxidative stress level and western blot were tested. Secondly, measured the effects of astaxanthin pretreatment on microRNA expression in a rat myocardial cell anoxia-reoxygenation injury model.Results: After anoxia-reoxygenation injury, in a dose dependent manner, astaxanthin increased cell viability, superoxide dismutase and glutathione peroxidase activity, decreased lactate dehydrogenase and malondialdehyde levels, downregulated protein expression of caspase-3, caspase-8, nuclear factor erythroid-2-related factor 2 and heme oxygenase-1, and upregulated the Bcl-2/Bax ratio. High-throughput sequencing and qPCR showed that microRNAs rno-miR-125b-5p and rno-let-7c-1-3p were differentially expressed (|log2| ≥ 0.585, q < 0.1) between the normal, anoxia-reoxygenation, and astaxanthin (1.25 μM) groups. Kyoto Encyclopedia of Genes and Genomes and GO Gene ontology pathway enrichment analyses showed that TNF signaling, axon guidance, NF-κB signaling pathway, and other pathways displayed differentially expressed microRNA target genes associated with myocardial injuries.Discussion: These results suggested that thetarget genes of rno-miR-125b-5p were enriched in inflammation and apoptosis-related signaling pathways. Also, the results imply that simultaneous targeting of these related signaling pathways could significantly prevent myocardial anoxia-reoxygenation injury in the presence of astaxanthin.
研究领域:
心血管生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2022
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IF 6.911
Lin-Lin Lu,Qin Zhang,Yu Gu,Xiang-Ling Li,Jing jing Xie
A novel type of core-shell “loading-type” nanomaterials , which integrated excellent biocompatibility, high loading capacity, efficient delivery, dual target recognition and response all-in-one, was fabricated for simultaneous imaging analysis of glutathione and microRNAs in living cells. Specifically, the core-shell “loading-type” nanomaterials (termed as [email protected] 2 ) were formed with mesoporous silica nanoparticles (MSNs) as core and a two-dimensional manganese dioxide nanosheets (MnO 2 ) as outer layer. Based on the excellent loading capability, the core MSNs was utilized as carriers for signal molecules of rhodamine 6G (R6G). Meanwhile, the shell MnO 2 acted as carriers for nucleic acid compounds, the locker for blocking R6G in the pore of MSNs, and reactant for reacting with redox species. Upon entering the cells, the specific redox reaction between the MnO 2 nanosheets and cellular glutathione (GSH) induced the removal of the locker layer from the MSNs, thereby triggering unlocking, releasing, and recovering the corresponding fluorescence of R6G. While encounter with miRNAs, the molecular beacons (MB) adsorbed on the MnO 2 nanosheets hybridized with target miRNA, which induced the conformational transition of the hairpin molecules, formed new secondary structures , and then recovered the fluorescence signal. Due to the each recovered fluorescence intensity was correlated with the corresponding target molecules, simultaneous detection of dual biomarkers was successfully achieved via the core-shell “loading-type” nanomaterials, which can provide more precise data guidance for diagnosis and disease treatment, and also own promising application in such research area.
研究领域:
纳米技术
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生物材料
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生物医学工程
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分析化学
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细胞生物学
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分子生物学
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医学诊断
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research
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2016
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IF 3.892
Min Jin,Yutao Wu,Yanwei Wang,Danqing Yu,Mei Yang,Feng Yang,Chun Feng,Ting Chen
MicroRNA-29a (miR-29a) has been extensively studied in tumor biology and fibrotic diseases, but little is known about its functional roles in vascular smooth muscle cell (VSMC) differentiation from embryonic stem cells (ESCs). Using well-established VSMC differentiation models, we have observed that miR-29a induces VSMC differentiation from mouse ESCs by negatively regulating YY1, a transcription factor that inhibits muscle cell differentiation and muscle-specific gene expression. Moreover, gene expression levels of three VSMC specific transcriptional factors were up-regulated by miR-29a over-expression, but down-regulated by miR-29a inhibition or YY1 over-expression. Taken together, our data demonstrate that miR-29a and its target gene, YY1, play a regulatory role in VSMC differentiation from ESCs in vitro and in vivo .
研究领域:
分子生物学
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干细胞研究
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心血管生物学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Yizhi Zhou,Qiang Liu
The sensitive and label-free detection of microRNA (miRNA) is crucial for the comprehension of miRNA-related pathological process, such as glioma. Here, we utilized a SYBR Green I (SG) catalytic photosensitization colorimetric reaction in conjunction with target recognition-induced exonuclease-iii (Exo-iii) assisted cascade toehold assembly amplification to achieve highly sensitive and label-free miRNA detection. In this research, the photosensitized generation of 1 O 2 by SG could directly oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) without the need for H 2 O 2 oxidation or enzyme catalysis, which simplifies the experimental procedures and renders the method highly stable. Furthermore, the Exo-iii enhances the target recognition induced catalytic chain assembly, thereby forming cascade signal amplification and providing the method with a significantly higher level of sensitivity than conventional colorimetric miRNA detection methods. Based on this, the proposed method exhibits a low limit of detection of 2.1 fM for miRNA-212 detection. Taking the merit of the high sensitivity, portability, and simplicity, the proposed method can serve as a highly effective nucleic acid detection tool and can facilitate the advancement of biosensors for point-of-care testing (POCT) and clinical disease diagnosis.
研究领域:
生物化学
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分子诊断
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医学检测
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）