DALTON TRANSACTIONS
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2023
·Vol. 52
·期 46
·17340-17348
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IF 4
Haiyun Liu,Na Ren,Yi Gao,Tingfan Wu,Boren Sui,Zhen Liu,Bin Chang,Man Huang,Hong Liu
As an important biomarker, microRNAs (miRNAs) play an important role in gene expression, and their detection has attracted increasing attention. In this study, a DNAzyme walker that could provide power to perform autonomous movement was designed. Based on the continuous mechanical motion characteristics of DNAzyme walker, a miRNA detection strategy for the self-assembly of AuNPs induced by the hairpin probe-guided DNAzyme walker “enzyme cleavage and walk” was established. In this strategy, DNAzyme walker continuously cleaved and walked on the hairpin probe on the surface of AuNPs to induce the continuous shedding of some segments of the hairpin probe. The remaining hairpin sequences on the surface of the AuNP pair with each other, causing the nanoparticles to self-assemble. This strategy uses the autonomous movement mechanism of DNAzyme walker to improve reaction efficiency and avoid the problem of using expensive and easily degradable proteases. Secondly, using dynamic light scattering technology as the signal output system, ultra-sensitive detection with a detection limit of 3.6 fM is achieved. In addition, this strategy has been successfully used to analyze target miRNAs in cancer cell samples.
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高影响因子
Journal of Inflammation Research
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2025
·
IF 4.1
Yinyin Zhao,Binyuan Jiang,Shengnan Zuo
Purpose Cucurbitacins have demonstrated anti-inflammatory effects and show promise for inflammatory bowel diseases. However, the underlying mechanisms by which cucurbitacins affect colitis remain largely unknown.Methods In this study, we investigated the impact of cucurbitacin IIa on dextran sulfate sodium (DSS)-induced colitis in rats and the alterations in intestinal extracellular vesicles (EVs). EVs were isolated and characterized, followed by analysis of the small RNAs and proteins encapsulated within them using small RNA sequencing and proteomics, respectively.Results Our results revealed that cucurbitacin IIa alleviated colitis symptoms in DSS-treated rats, along with changes in the morphology and composition of intestinal EVs. Notably, EVs from cucurbitacin IIa-treated rats also mitigated colitis symptoms in DSS-treated rats. Further analysis showed that cucurbitacin IIa modified the protein profiles and microRNA composition of EVs extracted from the feces of colitis rats. Specifically, microRNA-30b-5p, significantly increased by cucurbitacin IIa, was found to alleviate colitis symptoms in DSS-treated rats. In conclusion, cucurbitacin IIa appears to alleviate colitis by promoting the release of microRNA-30b-5p from host-derived extracellular vesicles.Conclusion These findings enhance our understanding of cucurbitacin IIa’s effects on intestinal health and offer potential new therapeutic targets for inflammatory bowel disease treatment.
研究领域:
药理学
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胃肠病学
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分子生物学
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 10
·5911-5925
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IF 4.486
Dafeng Yang,Zhousheng Yang,Lei Chen,Dabin Kuang,Yang Zou,Jie Li,Xu Deng,Songyuan Luo,Jianfang Luo,Jun He,Miao Yan,Guixia He,Yang Deng,Rong Li,Qiong Yuan,Yangzhao Zhou,Pei Jiang,Shenglan Tan
Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata , in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient ( Apoe − / − ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe − / − mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe − / − mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.
研究领域:
心血管疾病
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药理学
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分子生物学
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传统中药
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高影响因子
Journal of Orthopaedic Surgery and Research
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2023
·Vol. 18
·期 1
·1-12
·
IF 2.6
Su Hairong,Yang Yulan,Lv Wanchun,Li Xiaoli,Zhao Binxiu
Background Osteoporosis (OP) is a systemic skeletal disorder with increased bone fragility. Human bone marrow mesenchymal stem cells (hBMSCs) have multi-lineage differentiation ability, which may play important roles in osteoporosis. In this study, we aim to investigate the role of hBMSC-derived miR-382 in osteogenic differentiation.Methods The miRNA and mRNA expressions in peripheral blood monocytes between persons with high or low bone mineral density (BMD) were compared. Then we collected the hBMSC-secreted sEV and examined the dominant components. The over-expression of the miR-382 in MG63 cell and its progression of osteogenic differentiation were investigated by qRT-PCR, western blot and alizarin red staining. The interaction between miR-382 and SLIT2 was confirmed by dual-luciferase assay. The role of SLIT2 was also confirmed through up-regulation in MG63 cell, and the osteogenic differentiation-associated gene and protein were tested.Results According to bioinformatic analysis, a series of differential expressed genes between persons with high or low BMD were compared. After internalization of hBMSC-sEV in MG63 cells, we observed that the ability of osteogenic differentiation was significantly enhanced. Similarly, after up-regulation of miR-382 in MG63 cells, osteogenic differentiation was also promoted. According to the dual-luciferase assay, the targeting function of miR-382 in SLIT2 was demonstrated. Moreover, the benefits of hBMSC-sEV in osteogenesis were abrogated through up-regulation of SLIT2.Conclusion Our study provided evidence that miR-382-contained hBMSC-sEV held great promise in osteogenic differentiation in MG63 cells after internalization by targeting SLIT2, which can be served as molecular targets to develop effective therapy.
研究领域:
干细胞生物学
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分子生物学
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骨骼生物学
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再生医学
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高影响因子
eLife
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2019
·
IF 7.551
Xuefei Yan,Beibei Tang,Biao Chen,Yongli Shan,Huajun Yang,Reproducibility Project: Cancer Biology,Elizabeth Iorns,Rachel Tsui,Alexandria Denis,Nicole Perfito,Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2024
·Vol. 29
·期 1
·1-14
·
IF 2.8
Zhao Xun,Yuan WenQiang,Yang LiuChan,Yan Fang,Cui DeJun
Background Worldwide, ulcerative colitis (UC) is becoming increasingly fast growing. Ginsenoside Rh2 has been reported to alleviate UC. However, the latent biological mechanism of Rh2 in the treatment of UC remains uncertain. In this study, the goal was to determine the therapeutic effect of Rh2 on dextran sulfate sodium (DSS)-induced UC. Methods A DSS-induced UC mouse model was established and divided into 7 groups for Rh2 gavage and/or miR-125a-5p lentivirus injection (n = 10 per group). Colonic specimens were collected for phenotypic and pathological analysis. miR-125a-5p and specific protein 1 (SP1) expression, inflammation-related factors IL-6 and IL-10, and apoptosis were detected in mice. Human normal colon epithelial cell line NCM460 was treated with H 2 O 2 and ferric chloride hexahydrate to construct an in vitro cell model of colitis and induce ferroptosis. Independent sample t-test was used to compare cell proliferation, cell entry, apoptosis, and oxidative stress between the two groups. One way analysis of variance combined with the least significant difference t test was used for comparison between groups. Multiple time points were compared by repeated measurement analysis of variance. Results DSS-induced UC mice had significantly decreased body weight, increased disease activity index, decreased colon length, and decreased miR-125a-5p expression (all P < 0.05). In the DSS-induced mouse model, the expression of miR-125a-5p rebounded and ferroptosis was inhibited after Rh2 treatment (all P < 0.05). Inhibition of miR-125a-5p or upregulation of SP1 expression counteracted the protective effects of Rh2 on UC mice and ferroptosis cell models (all P < 0.05). Conclusions Rh2 mitigated DSS-induced colitis in mice and restrained ferroptosis by targeting miR-125a-5p. Downregulating miR-125a-5p or elevating SP1 could counteract the protective impacts of Rh2 on ferroptotic cells. The findings convey that Rh2 has a latent application value in the treatment of UC. Graphical Abstract
研究领域:
药理学
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分子生物学
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免疫学
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胃肠病学
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高影响因子
ANALYTICA CHIMICA ACTA
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2026
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IF 6.1
Kangzhe Cao,Fan Zhang,Jiakun Zhang,Jinjin Fu,Ping Lu,Jun-Tao Cao,Huiqiao Liu
Background MicroRNA-21 (miRNA-21) has emerged as a promising biomarker for early cancer diagnosis, yet its accurate quantification in complex biological matrices remains a significant challenge. Conventional SERS-based biosensors are inherently susceptible to non-specific adsorption of biomolecules and probe tags, which generates substantial background interference and severely compromises the signal-to-noise ratio (SNR) and detection fidelity. While various signal amplification strategies have been extensively explored, the critical issue of actively suppressing non-specific noise at the sensing interface has been largely overlooked, necessitating innovative approaches that can simultaneously enhance specific signals and minimize background interference. Results We develop an electrokinetic SERS biosensor that actively modulates the SNR through two sequential voltage-gated steps in a sandwich-structured detection format. A positive potential preconcentrates the negatively charged miRNA-21 targets and SERS probes at the electrode interface, significantly increasing their local concentration and accelerating specific hybridization kinetics, while a subsequent reverse potential acts as an electrostatic filter to selectively desorb non-specifically adsorbed probes, effectively purifying the sensing interface. This synergistic combination of preconcentration and separation efficiently decouples specific signals from non-specific interference, achieving a wide linear detection range from 1.0 × 10 −15 to 1.0 × 10 −10 M with an ultralow detection limit of 0.48 fM. The biosensor exhibits excellent selectivity in discriminating single-base mismatches and demonstrates robust analytical performance in human serum samples, with recoveries ranging from 95.4% to 104%. Significance This work introduces a novel paradigm for high-fidelity SERS biosensing by actively tuning the SNR through precise dual-action electrokinetic control. The strategy offers a generalizable, enzyme-free solution to the challenge of non-specific adsorption, critically enhancing both detection accuracy and practical applicability in complex biological matrices. The electrokinetic approach provides a versatile platform for reliable biomolecular analysis.
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ANALYST
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2025
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IF 3.3
Daqi Chen,Zhezhi Fang,Yachunyue Zhou,Ziyao Zeng,Jiancong Liang,Baian Zhu,Chaozhan Chen
MicroRNAs (miRNAs), as pivotal regulators of gene expression, are critically associated with the progression of cancer, neurodegenerative, and cardiovascular diseases. However, their detection remains challenging due to low sensitivity, background noise, and matrix interferences in complex biological samples, hindering clinical applications such as early tumor screening and liquid biopsy. Herein, we present a cascade-amplified fluorescence biosensor driven by the synergistic integration of exonuclease III (Exo III) and self-locking DNAzyme (SLD). This strategy exploits Exo III-mediated cyclic digestion of target-induced DNA/RNA heteroduplexes to release multiple signal conversion chains, while the SLD’s rigid conformational gate suppresses nonspecific catalysis until unlocked by target-specific molecular keys. The activated DNAzyme then drives secondary amplification through iterative cleavage of fluorophore-labeled reporters. This dual-amplification mechanism achieves label-free, isothermal detection of miRNA-155 with a linear range of 50 fM–10 pM and a limit of detection (LOD) of 4.96 fM. Notably, the sensor demonstrates robust specificity in serum matrices, effectively overcoming homologous miRNA cross-reactivity and complex biological interferences. By merging target recycling with conformation-gated catalysis, this platform offers a cost-effective, high-precision solution for miRNA profiling, holding significant promise for point-of-care diagnostics and liquid biopsy-based early cancer detection.
研究领域:
分子生物学
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肿瘤学
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转化医学
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生物传感
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临床检验
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Bioactive Materials
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2024
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IF 18
Hongyan Wei,Tiantian Xue,Fenfang Li,Enguo Ju,Haixia Wang,Mingqiang Li,Yu Tao
The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.
研究领域:
再生医学
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分子生物学
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干细胞生物学
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肝病学
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组织工程
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高影响因子
ACTA PAEDIATRICA
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2021
·Vol. 110
·期 7
·2221-2229
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IF 2.299
Jing Li,Meixue Chen,Jinfeng Wang,Lingling Lu,Xiang Li,Yuan Le
Aim This study aimed to profile the microRNA levels in Chinese Henoch-Schonlein purpura (HSP) children and to explore their association with inflammatory factors and T helper 17 (Th17)/regulatory T (Treg). Methods Forty-five HSP children and 27 healthy controls were enrolled in this study, and microRNA levels were profiled with a microRNA microarray. The levels of selected microRNAs were determined by quantitative real-time PCR, and the levels of serum IgA, interleukin-6, interleukin-10 and interleukin-17A were detected by enzyme-linked immunosorbent assay. Additionally, Th17 and Treg cells were analysed by flow cytometry. Results There were 9 up-regulated and 27 down-regulated microRNAs in the PBMCs of Chinese HSP children. Among them, miR-1-3p, miR-19b-1-5p and miR-29b-1-5p were up-regulated, while miR-483-5p and miR-1246 were down-regulated. Additionally, these selected microRNAs could differentiate HSP patients from healthy controls. Interestingly, miR-29b-1-5p was correlated with IgA, miR-19b-1-5p, miR-483-5p and miR-1246 were correlated with interleukin-6, while miR-1-3p and miR-1246 were correlated with Th17/Treg. Conclusion This study reveals that the altered microRNAs could differentiate HSP from the healthy, and were associated with inflammatory factors or Th17/Treg. It is indicated that alteration in these microRNAs may contribute to the HSP pathogenesis and may become therapeutic targets or diagnostic biomarkers for HSP.
研究领域:
儿科
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免疫学
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分子生物学
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PubMed
高影响因子
Small
·
2019
·Vol. 15
·期 41
·1903016
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IF 10.856
Nan Yan,Lin Lin,Caina Xu,Huayu Tian,Xuesi Chen
Developing tumor-responsive diagnosis and therapy strategies for tumor theranostics is still a challenge owing to their high accuracy and specificity. Herein, an AND logic gated–DNA nanodevice, based on the fluorescence nucleic acid probe and polymer-modified MnO 2 nanosheets, for glutathione (GSH)-gated miRNA-21 signal amplification and GSH-activated magnetic resonance (MR) imaging–guided chemodynamic therapy (CDT) is reported. In the presence of overexpressed miRNA and GSH (tumor cells), the nanodevice can be in situ activated and release significantly amplified fluorescence signals and MR signals. Conversely, the fluorescence signal is quenched and MR signal remains at the background level with low miRNA and GSH (normal cells), efficiently reducing the false-positive signals by more than 50%. Under the guide of miRNA profiling and MR imaging, the tumor-responsive hydroxyl radical ( · OH) can effectively kill tumor cells. Furthermore, the nanodevice shows catalase-like activity and glucose oxidase–like activity with the performance of O 2 production and glucose consumption. This is the first time to fabricate a tumor-responsive theranostic DNA nanodevice with tumor-specific signal amplification of microRNA and GSH-activated MR imaging for CDT, potential hypoxia relief and starvation therapy, which provides a new insight for designing smart theranostic strategies.
研究领域:
生物医学工程
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纳米技术
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诊疗学
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分子生物学
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癌症研究
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高影响因子
MICROCHEMICAL JOURNAL
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2020
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IF 3.594
Yihui Ma,Nianzu Liu,Zhenying Xu,Jingjing Wang,Xiliang Luo
The rapid, selective and ultrasensitive assaying of biomarkers remains a challenge relevant to biosensor/diagnostic applications. Herein, a promising electrochemical biosensor based on three-dimensional (3D) nanoporous conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) decorated with gold nanoparticles (AuNPs) was developed, in which methylene blue (MB) was employed as redox indicator for microRNA24 (miRNA24) detection. The unique porous construction was fabricated by a simple hard-template method and cyclic voltammetry (CV) electrochemical technique. AuNPs were electrodeposited onto the porous PEDOT surface to increase the interface conductivity and provide more active sites to load identification elements. The obtained porous biosensor based on conducting polymer PEDOT and AuNPs exhibited significantly enlarged specific surface area (about 2.4 times) and enhanced sensitivity (about 2.1 times), compared to the biosensor based on planar PEDOT. The developed porous biosensor achieved a miRNA24 quantification range from 1 fM to 10 nM with satisfying stability, high selectivity, and a low limit of detection (0.38 fM). The construction of biosensors based on porous conducting polymers decorated with AuNPs offers an effective strategy to increase the electroactive surface area of the sensing interfaces, so as to effectively enhance the sensitivity.
研究领域:
生物传感器
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电化学
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纳米技术
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分析化学
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分子诊断
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高影响因子
危险品化学品经营许可证（带存储）