ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Tiantian Xue,Hongyan Wei,Fenfang Li,Yixin Zhang,Yuanyuan Jin,Yanteng Xu,Hon Fai Chan,Yingying Xu,Yin-Xiong Li,Mingqiang Li,Yu Tao
Acute liver failure (ALF) involves extensive necrosis of liver cells and severe impairment of liver function. Hepatocyte transplantation holds promise for treating ALF by swiftly supporting liver functions and promoting liver regeneration. However, the scarcity of suitable cell sources requires strategies to obtain enough functional hepatocyte-like cells (HLCs) and optimize their in vivo transplantation efficiency. A DNA hexahedral nanostructure (DHN) is developed loaded with microRNA-122 to efficiently induce hepatic differentiation of human adipose-derived mesenchymal stem cells into HLCs. These HLCs can serve as alternative hepatocyte sources, as confirmed by expression of liver-specific genes and proteins, and the restoration of liver functions. To enhance in vivo survival efficiency of HLCs, a versatile scaffold is also created by 3D printing the calcium-cross-linked mixture bioink composed of sodium alginate, gelatin, and silk fibroin with excellent ROS scavenging capabilities. The scaffold is infused with chitosan-DHN hydrogel containing HLCs for tissue engineering orthotopic transplantation in CCl 4 -induced ALF mice. The transplanted composite scaffold-HLCs successfully repair tissue necrosis in the liver injury area of mice and regulate expressions of genes and proteins associated with inflammation, oxidative stress, and hepatocyte function. Collectively, this study offers a novel approach and strategy for identifying alternative hepatocyte sources and treating ALF.
研究领域:
生物医学工程
·
组织工程
·
干细胞生物学
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分子生物学
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纳米技术
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再生医学
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DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
·
IF 9.221
Yu-Yang Wei,Shao-Hua Wu,Qi-Meng Wang,Jian-Jun Sun
A novel split-type and signal-on photoelectrochemical (PEC) biosensor was proposed based on double-strand specific nuclease (DSN)-assisted recycling amplification coupled with photodeposited Ag enhanced BiVO 4 photoanode for sensitive detection of microRNA (miRNA)− 155. In the presence of target miRNA, the capture DNA (cDNA) modified with silver nanocube（AgNC）would hybridize with the miRNA, then DSN-assisted cycle amplification was triggered, leading to the release of AgNCs. The released AgNCs were acidolyzed and photodeposited on the BiVO 4 electrode. Compared with the BiVO 4 electrode, an enhanced photocurrent could be achieved at this obtained BiVO 4 /Ag electrode. And the morphology change from worm-like nanoparticles to nanosheets after Ag photodeposition was observed for the first time. This PEC signal enhancement was mainly contributed to the synergistic action of localized surface plasmon resonance (LSPR) effect of Ag, Schottky junction formed between BiVO 4 and Ag, and the formation of BiVO 4 nanosheets with larger specific surface area. The PEC signal enhancement was positively related to the miRNA-155 concentration, so this method could be used to sensitively and selectively detect miRNA-155. A limit of detection of 8 aM could be achieved. This strategy does not require layer-by-layer modification of the electrode, so it is easy to operate, and owns good stability.
研究领域:
生物化学
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分析化学
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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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产品关联
DOI
高影响因子
Bioengineered
·
2022
·
IF 6.832
Yuanmei Che,Jianglong He,Xiaopeng Li,Daxian Wu,Yi Zhang,Guicai Yuan
microRNAs, as small endogenous RNAs, influence umpteen sophisticated cellular biological functions regarding neurodegenerative and cerebrovascular diseases. Here, we interrogated miR-381-3p’s influence on BV2 activation and neurotoxicity in ischemic and hypoxic environment. Oxygen-glucose deprivation (OGD) was adopted to induce microglial activation and HT-22 neuron damage. Quantitative polymerase chain reaction (qRT-PCR) was taken to check miR-381-3p expression in OGD-elicited BV2 cells and HT-22 neurons. It transpired that miR-381-3p expression was lowered in BV2 cells and HT-22 cells elicited by OGD. miR-381-3p up-regulation remarkably hampered inflammatory mediator expression in BV2 cells induced by OGD and weakened HT22 neuron apoptosis. In vivo, miR-381-3p expression was abated in HI rats’ ischemic lesions, and miR-381-3p up-regulation could ameliorate inflammation and neuron apoptosis in their brain. C-C chemokine receptor type 2 (CCR2) was identified as the downstream target of miR-381-3p, and miR-381-3p suppressed the CCR2/NF-κB pathway to mitigate microglial activation and neurotoxicity. Therefore, we believed that miR-381-3p overexpression exerts anti-inflammation and anti-apoptosis in ischemic brain injury by targeting CCR2
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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脑血管疾病
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DOI
PubMed
高影响因子
ACS Sensors
·
2019
·
IF 6.944
Lin Shi,Yudie Sun,Lan Mi,Tao Li
Portable chemiluminescence (CL) imaging with a smartphone has shown a great promise for point-of-care testing of diseases, especially for acute myocardial infarction (AMI), which may occur abruptly. A challenge remains how to improve the imaging sensitivity that usually is several orders of magnitude lower than those of counterpart methodologies using the sophisticated equipment. Toward this goal, here, we report the target-triggered in situ growth of AuNP@hairpin-DNA nanoprobes into spherical nucleic acid enzymes (SNAzymes), which serve as both nanolabels and amplifiers for portable CL imaging of microRNAs (miRNAs) with an ultrahigh sensitivity comparable to that of the instrumental measurement under same conditions. A G-quadruplex (G4) DNA dense layer is dynamically produced on the gold nanocore via a DNAzyme machine-driven hairpin cleaving and captures the cofactor hemin to form the SNAzymes with higher peroxidase activity and stronger nuclease resistance than the commonly used G4 DNAzymes. The matured SNAzymes are then utilized as catalytic labels in a luminol-artesunate CL system for miRNA imaging with a smartphone as the portable detector. In this way, two AMI-related miRNAs, miRNA-499 and miRNA-133a, are successfully detected in real patients’ serum with a naked eye-visualized CL change at 10 fM, showing a 5 order of magnitude improvement on the sensitivity of visualizing the same disease markers in clinical circulating blood as compared to the reported strategy. In addition, a good selectivity of our developed CL imaging platform is demonstrated. These unique features make it promising to employ this portable imaging platform for clinical AMI diagnosis.
研究领域:
生物技术
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生物化学
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纳米技术
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即时诊断
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医疗器械
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2024
·
IF 1.6
Jianming Zhang,Yancheng Jiang,Yubin Wang,Zhishan Zhang
MicroRNAs (miRNAs) are endogenous, noncoding, and sequence-specific single-stranded RNA regulatory factors whose abnormal expression levels are closely related to various diseases, especially cancer, and are considered effective biomarkers for disease diagnosis and prognosis. Since the concentrations of miRNAs in the body are low and disease diagnosis by detecting single miRNAs may result in a high false positive, it is essential to construct a sensitive biosensor for the determination of multiple miRNAs. In this work, an enzyme-free signal amplification assay based on plasma-enhanced fluorescence (PEF) is reported for the one-step simultaneous determination of two miRNAs. Gold nanorods (AuNRs) were functionalized with fluorescein isothiocyanate (FAM)-tagged hairpin DNA1 (H1) and cyanine 5.5 (Cy5.5)-tagged hairpin DNA2 (H2). The fluorescence signals of FAM and Cy5.5 were quenched due to their proximity to the surface of the AuNRs. In the presence of target miRNA-21 and miRNA-155, H1 and H2 complemented miRNA-21 and miRNA-155, respectively, and the fluorescence signals of FAM and Cy5.5 were not only restored but amplified due to the plasma-enhanced fluorescence. A suitable linear range (0.1 to 10 nM) and low limits of detection for miRNA-21 (23 pM) and miRNA-155 (1.6 pM) were achieved. The developed assay for the one-step simultaneous measurement of two miRNAs is simple, fast and sensitive, exhibiting great potential for monitoring these biomarkers.
研究领域:
生物化学
·
分子生物学
·
医学诊断
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2017
·
IF 7.78
Shuzhen Yue,Tingting Zhao,Sai Bi,Zhipeng Zhang
High throughput analysis of miRNAs is of great significance to clinical and biomedical applications . In this work, we have developed a highly sensitive and selective chemiluminescence imaging array (CLIA) for simultaneous detection of three miRNAs with high throughput, easy operation and low cost. In this assay, three kinds of hairpins that can specially recognize respective miRNAs (miR-155, miR-let-7a and miR-141) are parallel modified on the magnetic beads (MBs). The employment of MBs enables quick sorting of multiplex targets in high yield and purity with high throughput. Upon introduction of the target miRNAs, they hybridize to the corresponding hairpins and initiate the DNA machines with the assistance of Klenow fragment exo- DNA polymerase and Nb.BbvCI NEase , achieving exponential amplification of targets. After that, the toehold-mediated strand displacement (TMSD) reactions are performed through sequential addition of displacement probes under magnetic separation, resulting in the release of HRP-tagged DNA hybrids in solution for CL imaging and recovery of MBs for repetitive use. This CLIA method demonstrates ultrahigh sensitivity with detection limits down to fM level, wide linear range over 5 orders of magnitude, excellent selectivity to distinguish one-base mismatched target miRNA, and good performance in real sample analysis. Together with the advantages of high throughput, easy operation, acceptable accuracy, and good recyclability and reproducibility, the proposed multiplex CLIA method holds great potential in practical applications, such as profiling the pattern of miRNA expression, disease screening, biomedical research, and so on.
研究领域:
生物医学工程
·
分子诊断学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
Yingshu Guo,Yujie Wang,Guangxu Yang,Jing-Juan Xu,Hong-Yuan Chen
Here, a mass-sensitive microRNA sensing surface is developed by utilizing a probe DNA/gold nanoparticles (GNP)/dendrimer composite coupling with an enzymatic amplification process. The probe DNA/GNP/dendrimer composite is prepared via the covalent coupling between the NH 2 groups in PAMAM or DNA and the COOH group on GNP. Target microRNA binds to a stem-loop-structured DNA on maganatic NPs, forming a heteroduplex . By enzyme recycling amplification, a large number of linker sequences are produced on MNPs . Via the combination of probe DNA , the linker DNA on MNPs and a capture DNA on gold chip, the DNA/GNP/dendrimer probe could be assembled on the surface of gold chip inducing a sensitive frequency response. It presents an excellent performance in microRNA-203 quantification with a detection linear range of 1.0×10 −11 –1.0×10 −9 M. Both the success in discriminating expressing miroRNA-203 in MCF-7 cell and the well agreement with the commercial qRT-PCR detection method implied its potential application in early cancer diagnosis for future.
研究领域:
生物传感器
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纳米技术
·
分子生物学
·
癌症诊断
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR NEUROSCIENCE
·
2025
·Vol. 76
·期 1
·4
·
IF 2.7
Wu Zhixuan,Wang Dianyi,Yao Jing,Zhang Yue,Liu Jiayu
Background Migraine is a complex neurological disorder. While acupuncture is effective in alleviating migraines, its molecular mechanisms remain unclear. This study aims to explore these mechanisms. Methods We used bioinformatics to identify differentially expressed microRNAs (miRNAs) in migraine patients after acupuncture. Subsequently, luciferase reporter assays were utilized to verify the interaction between miRNAs and their regulated target gene mRNAs. RT-qPCR and Western blot analyzed key miRNAs’ regulatory effects on target genes. We also employed Transwell migration assays and a nitroglycerin (NTG)-induced migraine mouse model to systematically evaluate acupuncture’s efficacy and mechanism. Results Bioinformatics analysis revealed a significant upregulation of Hsa-miR-550a-3-5p in the peripheral blood of migraine patients after acupuncture treatment. Hsa-miR-550a-3-5p could directly inhibit the mRNA and protein expression of platelet and endothelial cell adhesion molecule 1 (PECAM1), reducing nitroglycerin-induced human brain microvascular endothelial cells (HBMECs). Following the downregulation of PECAM1 by hsa-miR-550a-3-5p, the transendothelial migration capacity of monocytes-macrophages was significantly reduced, and reducing the secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Furthermore, it alleviates inflammation by regulating M2 macrophage polarization. In NTG-induced mice, acupuncture relieved migraine-like behaviors, an effect abolished by a miR-550a-3-5p inhibitor. Conclusion This study is the first to reveal that after acupuncture treatment, hsa-miR-550a-3-5p can be upregulated to target and inhibit PECAM1, reducing the transendothelial migration of inflammatory cells and the release of inflammatory cytokines, thereby alleviating migraine symptoms. This discovery provides scientific evidence for the efficacy of acupuncture and offers a new target for developing miRNA-based precision treatment strategies.
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DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 21
·7284-7296
·
IF 7.367
Shijin Bao,Shengnan Huang,Ying Liu,Yurong Hu,Weiping Wang,Mengfei Ji,Huili Li,Ning Xia Zhang,Chengzhi Song,Shaofeng Duan
Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.
研究领域:
分子生物学
·
纳米医学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JACS Au
·
2025
·
IF 8.7
Weiming Lin,Tao Ding,Die He,Nan Zhang,Haodong Li,Wenjian Luo,Zhongxia Wei,Min Ke,Sisi Jia,Chunhai Fan,Le Liang
Nanodiamonds (NDs) with nitrogen-vacancy (NV) centers are emerging as powerful quantum nanosensors (QNs) in biomedical applications due to their exceptional sensitivity. However, achieving optimal diagnostics performance necessitates both high sensitivity and selectivity; especially in practical biomedical settings, it remains challenging for QNs to provide quantitative analyses when multiple analytes are present. Here, we present a biosensing platform that integrates DNA logic gates (DLGs) with spin-based quantum sensing, termed DLG-QN for ultrasensitive and ultraselective diagnostics. Utilizing an AND DLG, both NDs and magnetic beads (MBs) are functionalized with hairpin DNA strands. In the presence of both miRNA-21 and miRNA-155─key biomarkers overexpressed in cancer─the hairpin DNAs undergo conformational changes that facilitate DNA-guided self-assembly of NDs and MBs, enriching the target signal. Resonant microwave modulation of ND fluorescence emission allows for high signal-to-noise ratio (SNR) detection by separating the signal from background fluorescence via spin-enhanced analysis. This platform demonstrated ultrasensitive and ultraselective detection of miRNA-21 and miRNA-155 with a limit of detection of 19.8 fM, highlighting its potential as a general biosensing strategy for precision diagnostics involving multiple biomarkers.
研究领域:
生物医学工程
·
分子诊断学
·
量子生物学
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产品关联
DOI
PubMed
高影响因子
NUCLEIC ACIDS RESEARCH
·
2025
·Vol. 53
·期 12
·
IF 13.1
Luo Tengshuo,Guan Ziyue,Liu Yunlong,Zhou Jun,Mergny Jean-Louis,Cheng Mingpan
A molecular beacon (MB) is an oligonucleotide probe with a stem-loop structure designed to fluoresce upon hybridization with a specific target nucleic acid. Herein, we introduce a novel i-motif DNA-based molecular beacon (iMB) designed for nucleic acid detection. DNA chemical sequencing showed that the iMB can be selectively opened when its target is present, thanks to the formation of a duplex between this target and the iMB recognition loop. Phase diagrams were introduced to analyze the binding properties between the iMB and its target, and to optimize the detection conditions with different combinations of pH and temperature. Benefiting from the environment-sensitive stability and special structural feature inherent to the i-motif, this iMB exhibits a controllable sensitivity and specificity through choosing appropriate temperature/pH combination and recognition loop position in the i-motif probe. Leveraging the duplex-specific nuclease (DSN) resistance of the i-motif, we significantly enhanced the sensitivity by more than four orders of magnitude through the implementation of a DSN-assisted amplification strategy. Finally, miRNAs in cell lines and patient plasma were detected by the iMBs, as validated via quantitative reverse transcription polymerase chain reaction (RT-qPCR). This research successfully broadens the structural repertoire of MB stems to include a pH- and temperature-responsive i-motif stem.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Yan-Li Zhu,Yan-Mei Lian,Ji-Kai Wang,Zeng-Ping Chen,Ru-Qin Yu
The multiple-metal-nanoparticle tagging strategy has generally been applied to the multiplexed detection of multiple analytes of interest such as microRNAs (miRNAs). Herein, it was used for the first time to improve both the specificity and sensitivity of a novel mass spectroscopic platform for miRNA detection. The mass spectroscopic platform was developed through the integration of the ligation reaction, hybridization chain reaction amplification, multiple-metal-nanoparticle tagging, and inductively coupled plasma mass spectrometry. The high specificity resulted from the adoption of the ligation reaction is further enhanced by the multiple-metal-nanoparticle tagging strategy. The combination of hybridization chain reaction amplification and metal nanoparticle tagging endows the proposed platform with the feature of high sensitivity. The proposed mass spectrometric platform achieved quite satisfactory quantitative results for Let-7a in real-world cell line samples with accuracy comparable to that of the real-time quantitative reverse-transcriptase polymerase chain reaction method. Its limit of detection and limit of quantification for Let-7a were experimentally determined to be about 0.5 and 10 fM, respectively. Furthermore, due to the unique way of utilizing the multiple-metal-nanoparticle tagging strategy, the proposed platform can unambiguously discriminate between the target miRNA and nontarget ones with single-nucleotide polymorphisms based on their response patterns defined by the relative mass spectral intensities among the multiple tagged metal elements and can also provide location information of the mismatched bases. Its unique advantages over conventional miRNA detection methods make the proposed platform a promising and alternative tool in the fields of clinical diagnosis and biomedical research.
研究领域:
分子生物学
·
分析化学
·
医学诊断
✓ 已验证
DOI
PubMed
高影响因子
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