JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Jiajun Wu,Xianfeng Lin,Jin Li,Ziyu Lv,Nuo Duan,Zhouping Wang,Shijia Wu
Acrylamide (AA) is a heat-processed potent food carcinogen that is widely used in industry, posing a significant risk to human health. Therefore, it is necessary to investigate the toxic effects and mechanism of AA. miR-21 is a representative biomarker during AA-induced carcinogenesis. Here, dual-color aggregation-induced emission nanoparticles (AIENPs) were developed for the detection and simultaneous imaging of AA and miR-21. AIENPs were synthesized by combining aggregation-induced emission (AIE) dyes and a poly (styrene-co-maleic anhydride) (PSMA) amphiphilic polymer modified with hairpin DNA. Upon AA intervention and aptamer recognition, cDNA was dissociated, leading to miR-21 overexpression and initiating the catalytic hairpin assembly cycle. Consequently, fluorescence quenching was observed due to FRET between AIENPs and labeled quenchers. The relative fluorescence intensities of dual-color AIENPs displayed good linear relationships with logarithmic AA and miR-21 concentrations. Moreover, there was a gradual decrease in dual-color AIENP fluorescence as the HepG2 cell concentration of AA (0–500 μM) and stimulation time (0–12 h) increased, making it possible to simultaneously image AA and AA-induced miR-21. The findings of this work are valuable for revealing the cytotoxic mechanism of AA.
研究领域:
纳米技术
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分子生物学
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毒理学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
YuLing Yang,JiaNi Zhang,SiWen Wu,Yu Deng,ShiHan Wang,Li Xie,XiaoPeng Li,Li Yang
Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects.
研究领域:
再生医学
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组织工程
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伤口愈合
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纳米技术
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生物材料
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2019
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IF 3.448
Li Sun,Tianhua Xu,Ying Chen,Wei Qu,Dan Sun,Xiaoyu Song,Quan Yuan,Li Yao
Pioglitazone has been demonstrated to exert anti-fibrotic and renoprotective effects. But the detailed pharmacological mechanisms have not been clearly revealed. The present study aimed to investigate the possible mechanisms of pioglitazone in these two effects. TGF-β1-stimulated HK-2 cells and unilateral ureteral obstruction (UUO) mice were used as in vitro and in vivo models. The results showed that pioglitazone inhibited Smad-2/3 phosphorylation, upregulated Smad-7 expression and downregulated miR-21-5p expression in TGF-β1-exposed HK-2 cells. In addition, miR-21-5p inhibitors replicated the anti-fibrotic effects of pioglitazone, and miR-21-5p mimics inhibited these effects. In in vivo study, pioglitazone attenuated UUO-induced renal fibrosis and significantly decreased the expressions of pro-fibrotic proteins. Whereas, agomir of miR-21-5p inhibited the renoprotective function of pioglitazone in UUO mice. In conclusion, the present data suggest that modulation of miR-21-5p/Smad-7 signal may be involved in the anti-fibrotic effect of pioglitazone in the kidney of UUO mice.
研究领域:
药理学
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 7
·1-13
·
IF 5.3
Zhao Tangtang,Xiao Ruilin,Li Yueqi,Ren Jierong,Niu Liyun,Chang Bingmei
With their regulated Boolean logic operations in vitro and in vivo, DNA logic circuits have shown great promise for target recognition and disease diagnosis. However, significant obstacles must be overcome to improve their operational efficiency and broaden their range of applications. In this study, we propose an Exo III-powered closed-loop DNA circuit (ECDC) architecture that integrates four highly efficient AND logic gates. The ECDC utilizes Exo III as the sole enzyme-activated actuator, simplifying the circuit design and ensuring optimal performance. Moreover, the use of Exo III enables a self-feedback (autocatalytic) mechanism in the dynamic switching between AND logic gates within this circulating logic circuit. After validating the signal flow and examining the impact of each AND logic gate on the regulation of the circuit, we demonstrate the intelligent determination of miR-21 using the carefully designed ECDC architecture in vitro. The proposed ECDC exhibits a linear detection range for miR-21 from 0 to 300 nM, with a limit of detection (LOD) of approximately 0.01 nM, surpassing most reported methods. It also shows excellent selectivity for miR-21 detection and holds potential for identifying and imaging live cancer cells. This study presents a practical and efficient strategy for monitoring various nucleic acid-based biomarkers in vitro and in vivo through specific sequence modifications, offering significant potential for early cancer diagnosis, bioanalysis, and prognostic clinical applications. Graphical abstract
研究领域:
分子生物学
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生物医学工程
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诊断学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2018
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IF 5.667
Xiang Ran,Zhen Liu,Zhenzhen Wang,Fang Pu,Jinsong Ren,Xiaogang Qu
High sensitive detection and monitoring of miRNAs in living cells have obtained considerable attention for clinical diagnosis of diseases. However, there are still enormous challenges for developing new method of quantification of miRNA in vivo. Herein, an intelligent MnO 2 -carried catalytic DNA machine (MCDM) was constructed for direct visualization of MicroRNAs in vivo with high selectivity and extremely low detection limit. MnO 2 nanosheets were used as a degradable carrier to introduce the DNA machine into cells. Benefiting from the enhanced permeability and retention (EPR) effect, the MnO 2 -carried probes could accumulate in tumor tissue, realizing a direct visualization of low concentration of miR-21 in the tumor of living animals in situ.
研究领域:
生物化学
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分子生物学
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医学诊断
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yanming Lai,Wei Xiao,Zhiwei Lei,Huiping Long,Jiting Deng,Yiyu Wang,Lu Tao,Xingxing Liu,Jinjun Wu,Qiwei Zhang,Donglin Cao,Heng Xiao
Exosomal microRNAs (miRNAs) serve as dependable and noninvasive biomarkers for early cancer diagnosis. However, the accurate and feasible detection of exosomal miRNAs is often hindered by their low abundance and the requirement of specialized equipment for miRNA detection. In this study, we present a novel approach, termed primer exchange reaction-based fluorescence emission with cascade RNA aptamers transcription (PERFECT) for the highly sensitive detection of exosomal miRNA. The design of this method involves the selective interaction of a DNA probe with the target miRNA, leading to its activation. Once activated, isothermal signal amplification and RNA aptamer transcription are initiated, resulting in an amplified fluorescent signal within 90 min. This method achieves a detection limit of 2.2 fM at 37 °C and 2.7 fM at room temperature (25 °C). We used the PERFECT technology to analyze miR-21 expression levels in cell extracts, cell-derived exosomes, and human plasma-derived exosomes, achieving a diagnostic accuracy of 93.6% in distinguishing hepatocellular carcinoma (HCC) patients. Overall, this study highlights its broad range of detection temperature, simplicity of the detection process, and strong potential for clinical application, rendering it a promising tool for early cancer diagnosis.
研究领域:
分子生物学
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医学诊断
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 144
·期 17
·5245-5253
·
IF 4.019
Yihan Zhao,Yu Wang,Su Liu,Chonglin Wang,Jiaxu Liang,Shasha Li,Xiaonan Qu,Rufeng Zhang,Jinghua Yu,Jiadong Huang
We have formulated a rapid and high-efficiency fluorescent biosensing platform based on a target-activated triple-helix molecular switch (THMS)-conformation-change-induced exponential rolling circular amplification (RCA) strategy for the ultrasensitive detection of miR-21. In this strategy, there are several aspects that are worthwhile. First, the functionalized THMS, comprising a typical triplex structure (T-A·T), specific recognition sequence for nicking endonuclease, complementary sequence for miR-21, and RCA product-annealing sequence, was concurrently used to perform signal transduction with one fluorophore and one quencher. As compared to the traditional double-helix molecular switches or molecular beacons, one of the biggest differentiating factors is that the properties of THMSs are independent of any specific binding sequence that they may contain. As far as we know, this is the first time that an ingeniously designed THMS not only contains the primer for exponential RCA, but also functions as the tracer for fluorescence assay. In the presence of miR-21, targets can induce conformation changes in THMS with the release of the trapped DNA segment (P), which, in turn, can activate the first run of the RCA process. Meanwhile, the RCA reaction is also initiated by the formation of a similar primer (SP) as the trapped DNA through a continuous “extension-nicking” reaction. Secondly, the resultant first-generation RCA product consists of numerous tandem repeated regions that can attach to countless THMSs, resulting in the release of the trapped DNA segment (P) for initiating the second run of the RCA reaction. Significantly, a large amount of THMSs were continuously consumed to yield a remarkably strong fluorescent signal. In addition, this biosensor was demonstrated to exhibit improved sensitivity owing to the high efficiency and rapid amplification kinetics of the exponential RCA and high selectivity toward miR-21 with a limit of detection as low as 1.1 aM. Hence, the target-mediated THMS-conformation-change-initiated exponential RCA strategy presents an optimal detection performance toward analytes for potential applications in related fundamental research and clinical diagnosis.
研究领域:
分子生物学
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生物化学
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医学诊断
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DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2025
·
IF 2.7
Yarong Yan,Shulei Xing,Jinghua Liu,Xinlin Yan,Yi Guan,Zhixin Jiang,Wei Zhang,Xuan Li
Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties; however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGFβ-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (αSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-κB/NLRP3/IL-1β signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGFβ-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGFβ/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.
研究领域:
药理学
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眼科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Xing Huang,Yanfei Zhang,Jun Chen,Lang Zhang,Yuzhi Xu,Wen Yin,Yakun Shi,Si-Yang Liu,Xiaoyong Zou,Zong Dai
Imaging of tumor-associated microRNAs (miRNAs) can provide abundant information for cancer diagnosis, whereas the occurrence of trace amounts of miRNAs in normal cells inevitably causes an undesired false-positive signal in the discrimination of cancer cells during miRNA imaging. In this study, we propose a dual-locked (D-locked) platform consisting of the enzyme/miRNA-D-locked DNAzyme sensor and the honeycomb MnO2 nanosponge (hMNS) nanocarrier for highly specific cancer cell imaging. For a proof-of-concept demonstration, apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 were chosen as key models. The hMNS nanocarrier can efficiently release the D-locked DNAzyme sensor in living cells due to the decomposition of hMNS by glutathione, which can also supply Mn2+ for DNAzyme cleavage. Ascribing to the smart design of the D-locked DNAzyme sensor, the fluorescence signal can only be generated by the synergistic response of APE1 and miR-21 that are overexpressed in cancer cells. Compared with the miRNA single-locked DNAzyme sensor and the small-molecule (ATP)/miRNA D-locked DNAzyme sensor, the proposed enzyme (APE1)/miRNA D-locked DNAzyme sensor exhibited 2.6-fold and 2.4-fold higher discrimination ratio (Fcancer/Fnormal) for cancer cell discrimination, respectively. Owing to the superior performance, the D-locked strategy can selectively generate a fluorescence signal in cancer cells, facilitating accurate discrimination of cancer both in vitro and in vivo. Furthermore, this D-locked platform is easily adaptable toward other target molecules by redesigning the DNA sequences. The outstanding performance and expansibility of this D-locked platform holds promising prospects for cancer diagnosis and related biomedical applications.
研究领域:
生物化学
·
分子生物学
·
癌症诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Chengcheng Wang,Cai Wang,Minyue Wang,Mengyue Wang,Qingbin Ni,Jingyi Sun,Baoliang Sun,Ying Wang
Spinal cord injury (SCI) is a serious neurological injury that is currently extremely difficult to cure clinically. SCI involves numerous pathophysiological processes, and microRNAs (miRNAs) play an important role in these processes. Meanwhile, miRNAs have received a lot of attention for their role in other diseases as well. Therefore, the detection of disease-related miRNAs is important for the study of disease development, treatment, and prognosis. With the rapid development of molecular biology, the traditional detection methods of miRNA can no longer meet the needs of experiments. Electrochemical detection methods are widely used because of their excellent detection performance. Here, we designed an electrochemical sensor prepared using borosilicate glass microneedle electrodes for real-time monitoring of miR-21–5p expression in vivo after SCI. The sensor showed a good linear relationship between the oxidation peak current value and the concentration of miR-21–5p in the concentration range 0–2 fM (Y = 12.025X + 90.396, R2 = 0.98). The limit of detection (LOD) of the sensor was 0.3667 fM. The experimental results showed that the borosilicate glass microneedle electrochemical sensor achieved fast, accurate, highly sensitive, highly specific, highly stable, and reproducible monitoring of miR-21–5p. More importantly, the electrochemical sensor has a better clinical translation prospect, which is important for the research of clinical diseases.
研究领域:
神经科学
·
分子生物学
·
医学工程
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产品关联
DOI
PubMed
高影响因子
ELECTROCHIMICA ACTA
·
2025
·
IF 5.6
Zhikun Zhang,Ying Shi,Zhengjie Li,Jilong Han,Zhiyan Chen,Fangfang Ma,Yanchao Qi,Yumin Liu
MicroRNA-21 (miR-21) has shown great promise as a biomarker for early cancer diagnosis. However, its trace-level abundance in clinical samples complicates point-of-care detection. Herein, we developed a new DNA-modified bimetallic dual-ligand MOF-based electrochemical sensor for highly sensitive and rapid detection of miR-21. The MOF was synthesized using 2,2′-bipyridine-5,5′-dicarboxylic acid (DPDC) and meso‑2,3-dimercaptosuccinic acid (DMSA) as organic linkers, with Ni²⁺/Co²⁺ serving as metal centers. Subsequently, the capture DNA (cDNA) was designed and modified MOF with high porosity and large surface area, significantly enhancing molecular interactions between the cDNA and target miR-21 to boost sensitivity. The developed biosensor exhibits a linear detection range of 10 fM to 100 nM, with a low detection limit of 10 fM and excellent specificity. This method effectively detects miR-21 in blood samples, showcasing strong clinical potential and providing a reliable platform for precision biosensing.
研究领域:
生物传感器
·
纳米技术
·
生物化学
·
分子诊断学
·
材料科学
·
电化学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Research
·
2022
·Vol. 26
·期 1
·1-20
·
IF 15.863
Sun Di,Mou Shan,Chen Lifeng,Yang Jie,Wang Rongrong,Zhong Aimei,Wang Wei,Tong Jing,Wang Zhenxing,Sun Jiaming
Background Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been found to have a great potential for soft tissue repair due to various biological functions, including pro-angiogenesis and low immunogenicity. However, the low yield and heterogeneity of MSC-EVs limited their clinical transformation. This study was designed to develop a novel adipose-derived stem cell engineered nanovesicles (ADSC-NVs) with high production and explore its pro-angiogenetic effect and application in adipose tissue regeneration.Methods Adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) were isolated from an EVs-free culture medium for human ADSCs (hADSCs). ADSC-NVs were prepared by sequentially extruding ADSCs followed by iodixanol density gradient ultracentrifugation and were compared with ADSC-EVs in morphology, size distribution, protein contents and yield. The pro-angiogenetic effect of ADSC-NVs in different doses (0, 5, 20 and 80 μg/mL) in vitro was determined using transwell assay, tube formation assay, western blot and qRT-PCR. In vivo, BALB/c nude mice were administered injection of a mixture of fat granules and different dose of ADSC-NVs and grafts were harvested at 12 weeks post-transplantation for further analysis. By analyzing the weight and volume of grafts and histological evaluation, we investigated the effect of ADSC-NVs in vessel formation and adipose tissue regeneration.Results Our results showed yield of purified ADSC-NVs was approximately 20 times more than that of ADSC-EVs secreted by the same number of ADSCs. In vitro, both ADSC-NVs and ADSC-EVs exhibited a dose-dependent pro-angiogenetic effect, despite their distinct miRNA profiles. These effects of ADSC-NVs may be mediated by enriched miR-21-5p via PTEN inhibition and PI3K/p-Akt signaling activation. Furthermore, after a mixed injection of ADSC-NVs, vessel formation and adipose regeneration were observed in vivo in fat implants.Conclusion sOur study developed a potent alternative of ADSC-EVs. ADSC-NVs have a high pro-angiogenesis potential and can be used as cell-free therapeutic biomaterials in soft tissue regeneration.
研究领域:
组织工程
·
再生医学
·
干细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）