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MEDICAL SCIENCE MONITOR · 2016 · IF 1.405

Lactation-Related MicroRNA Expression in Microvesicles of Human Umbilical Cord Blood

De-jing Wang,Chen-meiyi Wang,Yi-ting Wang,Hai Qiao,Liao-qiong Fang,Zhi-biao Wang

Background The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. Material/Methods Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and β-casein secretion was detected by ELISA. Results Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of β-casein was observed after 96 h from cells exposed to MVs (P<0.05). Conclusions Umbilical cord blood MVs contain many lactation-related miRNAs and can induce β-casein production by HBL-100 cells in vitro . Thus, umbilical cord blood MVs may mediate secretion of β-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.

研究领域: 妇产科学 · 分子生物学 · 细胞生物学
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ANALYTICAL CHEMISTRY · 2026 · IF 7.3

Precise Artificial Intelligence Nanomotor Tracking-Powered Amplification-Free Digital MicroRNA Sensing

Jingjing Shi,Zuhua Yu,Hui Tian,Wenjiao Fan,Wei Ren,Chenghui Liu

Digital assays have become a state-of-the-art technology for the sensing of nucleic acid molecules. Nevertheless, most of the prevalent digital nucleic acid assays heavily rely on sealed microchambers and sophisticated nucleic acid amplification strategies to achieve an end-point digital signal readout. Herein, we proposed an artificial intelligence (AI)-facilitated, digital fluorescence nanomotor tracking-powered assay (AI-dFNA) for one-step, amplification-free, and highly sensitive detection of microRNAs (miRNAs). In this design, even a single target miRNA-templated amplification-free ligation can introduce a sufficient driving force on the surface of a fully open fluorescence nanoparticle to cause remarkable motion behaviors. With the assistance of a self-developed AI algorithm, clear discrimination of positive and negative fluorescent nanomotors can be achieved, enabling real-time digital miRNA sensing. The AI-dFNA avoids the use of enclosed microchambers and intricate signal amplification techniques, which could even identify varying fluorescence colors of nanomotors to allow for the analysis of different kinds of miRNA molecules, pioneering a new direction toward next-generation digital nucleic acid sensing.

✓ 已验证 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

Liposome-mediated EC-SERS signal boost enables ultrasensitive detection of microRNA

Kangzhe Cao,Jinjin Fu,Fan Zhang,Jiakun Zhang,Fei Sun,Yanhao Qin,Jun-Tao Cao,Yong Lei,Huiqiao Liu

Aberrant microRNA (miRNA) expression is a critical biomarker for various diseases, yet its low abundance in biofluids poses significant detection challenges, limiting clinical utility. To overcome the sensitivity limitations of conventional methods, this paper developed a novel liposome-assisted electrochemical surface-enhanced Raman scattering (EC-SERS) sensor for ultrasensitive miRNA detection. This platform uniquely integrates three synergistic amplification strategies: (1) catalytic hairpin assembly (CHA) for exponential target miRNA recycling and capture, (2) high-capacity liposomal nanocarriers densely loaded with cationic Rhodamine 6G (R6G) SERS reporters, and (3) a low-cost silver nanowire-coated screen-printed electrode (AgNW-SPE) generating intense electromagnetic fields under electrochemical modulation. Target miRNA initiates CHA cycling, immobilizing numerous DNA-tagged liposome probes on the SPE. Subsequent electrostatic attraction between the anionic AgNW-SPE and cationic R6G released from lysed liposomes concentrates the reporters at electromagnetic hotspots on the nanowires. This synergistic cascade enables ultrasensitive and specific detection. The EC-SERS sensor achieves a remarkably low detection limit of 28 fM and a wide linear range (1.0 × 10 −13 to 1.0 × 10 −9  M) for target miRNA, with high specificity against mismatched sequences. Demonstrated in complex biological serum samples, this robust and cost-effective platform provides a powerful tool for highly sensitive miRNA profiling. It holds significant potential for advancing biomarker discovery, enabling early diagnosis of disease, and facilitating personalized therapeutic strategies within precision medicine.

研究领域: 生物分析化学 · 纳米技术 · 分子诊断学 · 生物传感器 · RNA生物学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

A chirality/microRNA dual-gating theranostic nanomachine for gene silencing therapy

Zhan Huang,Xing Huang,Yanfei Zhang,Meng Chen,Shaoqiang Wen,Zhou Zhang,Zong Dai,Xiaoyong Zou,Si-Yang Liu

DNAzyme-based gene silencing is a promising cancer therapy technology, while its efficiency and safety issues still need to be addressed. In this study, we developed a chirality/microRNA dual-gating theranostic nanomachine for messenger RNA (mRNA) gene silencing therapy with enhanced targeting towards human cervical cancer (HeLa) cells. The chiral nanoparticle, an emerging material with unique chirality-induced properties, e.g. chirality-dependent cellular uptake, has been widely applied in biomedical fields. The L-type gold nanoparticles (L-AuNPs) are used as the nanocarrier with the first “chirality-gating”. L-AuNPs showed 2.4-fold uptake efficiency for HeLa cells comparing to normal cell, as well as 2.2-fold uptake efficiency in cancer cell comparing to D-type gold nanoparticles (D-AuNPs), which exhibited no cancer cell targeting effect. Moreover, an entropy-driven-DNAzyme (EDz) circuit that can release numerous DNAzyme and fluorescence probes with the trigger of single microRNA (miRNA) conducted the theranostic role of both miRNA imaging and gene silencing, constituting the second “miRNA gating”. Ascribing to the prominent targeting nanocarrier L-AuNPs, the miRNA imaging sensitivity and gene silencing therapy efficiency were improved by 2.6- and 5.0-fold, respectively, comparing to those by D-AuNPs. In general, this dual-gating nanomachine, designed with a powerful yet simple strategy, has showed great prospects in optimizing delivery specificity and avoiding off-target toxicities.

研究领域: 癌症治疗 · 纳米技术 · 分子生物学 · 生物医学工程 · 基因治疗
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

Ultrasensitive and Facile Detection of MicroRNA via a Portable Pressure Meter

Lu Shi,Jing Lei,Bei Zhang,Baoxin Li,Chaoyong James Yang,Yan Jin

The upregulation of microRNA (miRNA) is highly related with some kinds of tumor, such as breast, prostate, lung, and pancreatic cancers. Therefore, for an important tumor biomarker, the point-of-care testing (POCT) of miRNA is of significant importance and is in great demand for disease diagnosis and clinical prognoses. Herein, a POCT assay for miRNA detection was developed via a portable pressure meter. Two hairpin DNA probes, H1 and H2, were ingeniously designed and functionalized with magnetic beads (MBs) and platinum nanoparticles (PtNPs), respectively, to form MBs-H1 and PtNPs-H2 complexes. In the presence of target microRNA 21 (miR-21), the cyclic strand displacement reaction (SDR) between MBs-H1 and PtNPs-H2 was triggered to continuously form the MBs-H1/PtNPs-H2 duplex. Owing to the amplification of cyclic SDR, numerous PtNPs were enriched onto the surface of MBs to catalytically decompose H2O2 for the generation of much O2. The gas pressure value has a linear relationship with the logarithmic value of miR-21 concentration in the range of 10 fM to 10 pM. The limit of detection is 7.6 fM, which is more sensitive than that in a number of previous reports. Hairpin DNA probes and magnetic separation highly ensured the specificity and reliability. Single-base mutation was easily discriminated, and the detection of miR-21 in the serum sample achieved satisfactory result. Therefore, it offers a reliable POCT strategy for the detection of miRNA, which is of great theoretical and practical importance for POCT clinical diagnostics.

CAS / MDL: 16941-12-1
研究领域: 生物化学 · 医学诊断 · 分子生物学
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ANALYTICAL CHEMISTRY · 2022 · IF 8.008

Mitochondria MicroRNA Spatial Imaging via pH-Responsive Exonuclease-Assisted AIE Nanoreporter

Jinya Du,Yuchun Qiao,Xiangdan Meng,Wei Wei,Wenhao Dai,Lingzhi Yang,Changying Yang,Haifeng Dong

Mitochondrial microRNAs (mitomiRs) critically orchestrate mitochondrial functions. Spatial imaging of mitomiRs is essential to understand its clinical value in diagnosis and prognosis. However, the direct monitoring of mitomiRs in living cells remains a key challenge. Herein, we report an AIE nanoreporter strategy for mitomiRs imaging in living cells through pH-controlled exonuclease (Exo)-assisted target cycle signal amplification. The AIE-labeled DNA detection probes are conjugated on Exo III encapsulated polymeric nanoparticles (NPs) via consecutive adenines (polyA). The amplified sensing functions are off during the cytoplasm delivery process, and it can be spatially switched from off to on when in the alkaline mitochondria (about pH 8) after triphenylphosphonium (TPP)-mediated mitochondrial targeting. Where the NPs degraded to release Exo III and cancer-specific mitomiRs hybridize with AIE-labeled DNA detection probes to expose the cleavage site of released Exo III, enabling spatially restricted mitomiRs imaging. The mitomiRs expression fluctuation was also realized. This study contributes to a facile strategy that could easily extend to a broad application for the understanding of mitomiRs-related pathological processes.

CAS / MDL: 7758-99-8 134-03-2
研究领域: 生物学 · 生物化学 · 分子生物学 · 癌症研究 · 纳米技术
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BIOSENSORS & BIOELECTRONICS · 2023 · IF 12.6

Functionalized nanopores based on hybridization chain reaction: Fabrication and microRNA sensing

Xia Qiu,Jingyi Dong,Qingshan Dai,Mimi Huang,Yongxin Li

Enzyme-free hybridization chain reaction (HCR) technology is often used as a signal amplification tool for the detection of different targets. In this study, an ultrasensitive and label-free method for detecting miRNA-21 was developed using the nanopore ionic current rectification (ICR) technology coupled with HCR technology. The probe oligonucleotide (DNA1) was combined with the gold-coated nanopore through the Au–S bond to form a DNA1-functionalized gold-coated nanopore (DNA1-Au-coated nanopore). Since miRNA-21 is partially complementary to DNA1, it can be selectively recognized by DNA1-functionalized gold-coated nanopores. The target (miRNA-21) can induce the opening of hairpin DNA and HCR reaction after the introduction of hairpin DNA H1 and H2. The concentration of miRNA-21 will affect the combination of H1 and H2 on the inner wall of the nanopore, and its surface charge will change with the internal modification, thereby changing the ion current rectification ratio . Under the condition that the concentration of H1, H2 and HCR reaction time are constant, the change of ICR ratio is linearly correlated with the logarithm of miRNA-21 concentration within a certain range, which shows that the sensing strategy we designed can achieve target miRNA-21 detection. This ultrasensitive miRNA holds great promise in the field of cancer diagnosis.

研究领域: 生物化学 · 分子生物学 · 纳米技术 · 医学诊断
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TALANTA · 2019 · IF 4.916

Electrochemical detection of microRNAs based on AuNPs/CNNS nanocomposite with Duplex-specific nuclease assisted target recycling to improve the sensitivity

Xiangyu Ma,Haoran Xu,Kun Qian,Martha Kandawa-Schulz,Weimin Miao,Yihong Wang

MicroRNAs (miRNAs) are important biomarkers in early diagnosis of disease. In this work, we developed a simple and effective electrochemical biosensor based on Au nanoparticles (AuNPs)/Carbon nitride nanosheet (CNNS) nanocomposite for the miRNAs detection. Duplex-specific nuclease (DSN) and hairpin structure probe were utilized to improve the sensitivity and selectivity respectively. In the presence of miRNA-21, the signal molecule could be released from the surface of the electrode and decrease the current peak in square wave voltammetry (SWV) test. Under the optimal conditions, the reported biosensor showed that the detection range of miRNA-21 is from 10 fM to 1 nM and detection limit is as low as 2.9 fM. Furthermore, the detection of miRNA-21 added in serum samples indicates the developed biosensor with good selectivity, stability and reproducibility which verify its potential to be used in the early diagnosis of diseases.

研究领域: 生物化学 · 分子生物学 · 医学诊断
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Multichannel Paper Chip-Based Gas Pressure Bioassay for Simultaneous Detection of Multiple MicroRNAs

Lu Shi,Wei Liu,Baoxin Li,Chaoyong James Yang,Yan Jin

Simultaneous detection of multi-biomarkers not only enhances the accuracy of disease diagnosis but also improves detection efficiency and reduces cost. It is vital to achieve portable, simple, low-cost, and simultaneous detection of biomarkers for point-of-care (POC) diagnostics in a low-resource setting. Herein, a multichannel paper chip-based gas pressure bioassay was developed for the simultaneous detection of multiple biomarkers by combining multichannel paper chips with a portable gas pressure meter. Four DNA tetrahedral probes (DTPs) were used as capture probes and were immobilized in different detection zones of the paper chips to improve hybridization efficiency and reduce nonspecific adsorption. The formation of a sandwich structure between target microRNAs (miRNAs), the capture probe, and platinum nanoparticles (PtNPs)-modified complementary DNA (PtNPs-cDNA) transformed biomolecular recognition into quantitative detection of gas pressure. Four lung cancer-related miRNAs were detected simultaneously by a portable gas pressure meter. There is a good linear relationship between gas pressure and the logarithm of miRNA concentration in the range of 10 pM to 100 nM. Compared with single-stranded DNA capture probe, the signal-to-noise (S/N) of DNA tetrahedral probes improved more than 3 times. Using ring-oven washing, the unbound reagents in all channels of the paper chip were simultaneously and continuously washed away, leading to a more cheap, simple, and fast separation than magnetic separation. Therefore, it offers a promising multichannel paper chip-based gas pressure bioassay for portable and simultaneous detection of multiple biomarkers.

CAS / MDL: 16941-12-1
研究领域: 生物医学工程 · 分子诊断学 · 纳米技术
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CELLULOSE · 2024 ·Vol. 31 ·期 6 ·3645-3656 · IF 4.9

A multifunctional cellulose nanocomposite with targeted fluorescence imaging and photothermal effects on breast cancer cells

Hu Guizhen,Ning Juan,Wu Tian,Li Yuanjie,Nie Yamin,Lei Jiandu,Zhou Yanmei

Cellulose nanocrystals (CNCs) and polydopamine (PDA) have shown great application potential in the biomedical field due to their excellent biocompatibility. Using PDA@CNC as a carrier to construct functional nanocomposites for targeted fluorescence imaging of tumor cells and effective cancer treatment can expand the applications of CNCs in tumor diagnosis and treatment. Here, we conveniently modified microRNA-21 inhibitors (miRNAi) on PDA@CNC to construct a multifunctional nanocomposite (FAM-miRNAi@PDA@CNC) for achieving in situ fluorescence imaging of tumor biomarkers and photothermal effects to induce death of breast cancer cells. The overexpressed miRNA-21 in breast cancer cells hybridizes with FAM-miRNAi, triggering green fluorescence of FAM to recognize breast cancer cells. The rod-shaped morphology of FAM-miRNAi@PDA@CNC can effectively promote the endocytosis of FAM-miRNAi@PDA@CNC by the cell membrane. In addition, CNCs can stabilize the photothermal performance of PDA, and the photothermal conversion efficiency of PDA@CNC reached up to 61.66%, which will help FAM-miRNAi@PDA@CNC to achieve 70% apoptosis rate of breast cancer cells under 808 nm laser irradiation. The design of FAM-miRNAi@PDA@CNC provides a valuable pathway for CNCs utilization in biomedicine and accurate diagnosis and treatment of breast cancer.

CAS / MDL: 62-31-7 68-04-2 78-10-4
研究领域: 生物医学 · 肿瘤学 · 纳米医学
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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Enzyme-Free and Triple Sensitivity Amplification for Electrochemical Detection of Exosomal microRNA

Wenting Cheng,Han Pan,Jinhua Chen,Miao He,Zhongyun Wang,Yang Xiang

Exosomal miRNAs, particularly miRNA-21, are promising cancer biomarkers. Current enzyme-dependent detection methods face challenges, such as environmental limitations and high costs. In contrast, enzyme-independent sensors are highly desirable for on-site, miniaturized, and cost-effective miRNA detection. To address these limitations, we developed a nonenzymatic electrochemical sensor featuring a triple-signal amplification system for ultrasensitive detection of miRNA-21. This sensor utilizes cascade toehold-mediated strand displacement reactions to activate molecular machines triggered by target miRNA, generating biotinylated-and-thiol-modified double-stranded DNA for stable immobilization on a gold electrode. Preprepared biotinylated tetrahedron DNA (TDNA)-mediated hybridization chain reaction probes are then linked to the electrode via streptavidin–biotin binding. This amplification process allows for significant DNA duplex immobilization, with electroactive [Ru(NH3)6]3+ (RuHex) adsorbed onto them, producing a robust electrochemical signal. This approach enables accurate detection of miRNA-21 at concentrations as low as 0.43 fM, with a linear range from 1 fM to 1 nM. Clinical testing demonstrates its potential for cancer diagnostics.

研究领域: 生物化学 · 医学诊断 · 分子生物学
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TALANTA · 2019 · IF 4.916

Nickel-phosphate pompon flowers nanostructured network enables the sensitive detection of microRNA

Palanisamy Kannan,Thandavarayan Maiyalagan,Bingyong Lin,Wang Lei,Chen Jie,Longhua Guo,Zhongqing Jiang,Shun Mao,Palaniappan Subramanian

An electrochemical immuno-nanogenosensor is developed based on noble-metal-free nickel phosphate nanostructure (NiPNs) as an excellent biocompatible material for miRNA detection in blood serum and urine samples without using indicators for the first time. The pompon flower-like morphology of NiPNs is synthesized, and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction pattern (XRD), fourier transform-infrared spectroscopy (FT-IR), and electrochemical impedance methods. The novel NiPNs nanostructured interface was constructed by coordinate covalent bonding between Ni and phosphate group of probe DNA . The constructed NiPNs- p -DNA surface served as the amplified hybridization platform enabling efficient access to numerous target microRNA sequences. As a result, the developed NiPFNs biosensing platform displayed excellent sensitivity, selectivity , and ultralow experimental limit-of-detection (LOD) of 0.034 pM (S/N = 3) as compared with other Ni phosphide nanostructures. This simple and efficient approach is highly suitable for the development of point-of-care detection systems. To the extent of our knowledge, this is the first report on trace level detection of miRNAs employing non-noble Ni metal nanostructures based biosensing platform.

研究领域: 生物化学 · 纳米技术 · 电化学 · 生物传感器 · 医学诊断
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