Plant Gene
·
2021
·
IF 0
Hu Zhao,Xiaopu Shi,Cheng Shen,Caifeng Chen,Jiyuan Liu,Changqing Qu
Toon bud is rich in polyphenols and flavonoids, which not only have nutritional value but also have health benefits. However, the molecular mechanisms of flavonoid accumulation during storage remain unclear. In our report, small RNA libraries from toon buds were synthesized after three storage period (0, 3, and 5 days) at 4 °C. Overall, 303 homologous sequences with known microRNA (conserved miRNAs homology) and 19 putative novel miRNAs were obtained using Illumina sequencing technology. Furthermore, the potential target unigenes of these miRNAs were predicted. Of the predicted miRNAs and their target unigenes, 17 conserved miRNAs and their target unigenes were confirmed by quantitative real-time PCR (qRT-PCR). Exactly 11 miRNAs involved in the flavonoid pathway and 6 miRNAs targeting transcription factors displayed significant correlation with flavonoid accumulation in toon buds. The findings will be helpful for better understanding flavonoid accumulation in toon buds during storage.
研究领域:
植物科学
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分子生物学
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食品科学
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DOI
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Tianyue Wang,Qianlan Zhou,Yunxiao Shang
Airway remodeling happens in childhood asthma, in parallel with, but not necessarily subsequent to, airway inflammation. The differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal-transition (EMT) is one of the mechanisms underlying airway remodeling. This study aimed at identifying novel molecules involved in pediatric asthma-associated airway remodeling. Asthma model was established by challenging C57BL/6 mouse pups with ovalbumin (OVA). We found that the expression of Cadherin 11 (CDH11), a type II cadherin, was increased by OVA treatments in the airway epithelium. Our earlier microarray data suggested miRNA-451a-5p (miRNA-451a) as a potential regulator of CDH11. In contrast to CDH11, miRNA-451a expression decreased in the asthmatic lung. MiRNA-451a was then packaged into a lentivirus vector and systematically given to the asthmatic pups. Our data indicated that OVA-induced infiltration of inflammatory cells, including eosnophils, neutrophils, macrophages and lymphocytes, was reduced by miRNA-451a over-expression. EMT was initiated in asthmatic mice as demonstrated by increased alpha-smooth muscle actin (α-SMA) positive cells present in airway epithelium, which was inhibited by miRNA-451a. CDH11 elevation in vivo was also inhibited by miRNA-451a. Dual-Luciferase analysis further showed CDH11 as a novel valid target of miRNA-451a. Additionally, in vitro, EMT was triggered in human 16HBE airway epithelial cells by pro-fibrotic transforming growth factor β (TGF-β). Corresponding to the anti-EMT effects observed in vivo , miRNA-451a also inhibited TGF-β-induced collagen deposition in cultured airway epithelial cells by targeting in CDH11. In summary, our study demonstrates that the deregulated miRNA-451a-CDH11 axis contributes to airway remodeling in childhood asthma.
研究领域:
分子生物学
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呼吸医学
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儿科
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免疫学
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2023
·Vol. 18
·期 3
·035010
·
IF 4
Fu Zhang,Zhuo Yao,Piaopiao Jin,Mengqiu Xu,Qida Hu,Yuxuan Chen,Risheng Que,Tingbo Liang
Gemcitabine (Gem) has been recommended as a first-line clinical chemotherapeutics for pancreatic ductal adenocarcinoma (PDAC) treatment. Gem treatment could generate chemoresistance associated with abnormal expressions of multiple miRNAs. In the PDAC setting, miRNA-21 (miR-21) overexpression is an important contributing factor of inducing Gem chemoresistance. Inhibition of miR-21 can significantly increase Gem chemosensitivity, which requires an efficient delivery platform to conduct combinational Gem and miR-21 siRNA (miR-21i) therapy. Herein, we synthesized a tumor microenvironment (TME) stimuli-responsive poly(beta-amino ester)s (PBAE)-based polymer nano-prodrug (miR-21i@HA-Gem-SS-P12) that could co-deliver miR-21 siRNA and Gem. The disulfide linkages conjugating GEM onto PBAE can be triggered by elevated reduction stimulus in TME to release the cargo Gem. The hyaluronic acid (HA) fabrication further improved the drug accumulation at the tumor site. Benefiting from the multiple functional improvements and synergism between Gem and miR-21i, the miR-21i@HA-Gem-SS-P12 nano-prodrugs displayed superior tumor inhibition in PDAC in vitro and in vivo. This study established an effective stimuli-responsive nano-prodrug strategy for cooperative treatment with small molecule agents and nucleotide modulators in PDAC.
研究领域:
药学
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癌症生物学
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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
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Jiajun Zhong,Minghao Ge,Tongxu Gu,Tong Wang,Zhizhou Liu,Pengli Bai
Single-nanoparticle counting (SNPC) based on fluorescent tag (FT) stands out for its capacity to achieve amplification-free and sensitive detection of biomarkers. The stability and luminescence of FT are important to the sensitivity and reliability of SPNC. In this work, we developed novel perovskite/silica nanocomposites by in-situ nanoconfined growth of CsPbBr 3 nanocrystals inside mesoporous structure of silica nanoparticles. PbBr(OH) was formed in an alkaline-assisted reaction triggered by water on the surface of CsPbBr 3 nanocrystals. The as-obtained nanocomposites, featuring dual protection from silica matrix and PbBr(OH), exhibited high absolute photoluminescence quantum yield (PLQY) of 86.5% and demonstrated outstanding PL stability confronting with water, heat, ultrasound and UV-irradiation, which is desired by SNPC-based biosensor. Thereafter, these nanocomposites were used to construct an operationally friendly SNPC assay for the amplification-free quantification of cancer-associated miRNA. Quantitative detection of miRNA could be accomplished by directly counting the number of nanocomposites using a flow cytometer in this assay. This strategy did not ask for multiple washing steps and demonstrated specific and sensitive detection of miRNA 21, which exhibited a dynamic range of 1–1000 pM and limit of detection of 79 amol. The employment of highly stable perovskite/silica nanocomposites improved the test reliability and stability of SNPC, revealing the vast potential of perovskites in biosensing.
研究领域:
材料科学
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纳米技术
·
生物传感器
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
COMPUTERS IN BIOLOGY AND MEDICINE
·
2024
·
IF 7
Jianan Li,Yan Sun,Haoran Bi
Diazinon (DZN), a persistent organophosphate insecticide, has been associated with neurotoxic effects, particularly in the hippocampus. However, the specific molecular mechanisms of DZN-induced hippocampal toxicity remain unknown. In this study, we analyzed the mRNA and miRNA expression patterns of HT22 cells following exposure to DZN (125 μM), and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted subsequently. The integration of miRNA sequencing (miRNA-seq) and mRNA sequencing (mRNA-seq) data identified 33 differentially expressed miRNAs (DEMIs, 15 up-regulated and 18 down-regulated) and 271 differentially expressed mRNAs (DEMs, 69 up-regulated and 202 down-regulated) targeted by the DEMIs. Moreover, the 3 most central mRNAs (ITGAV, FN1, and EGFR) and 7 associated miRNAs (mmu-miR-700-5p, mmu-miR-26a-2-3p, mmu-miR-452-3p, mmu-miR-25-3p, mmu-miR-582-5p, mmu-miR-467a-5p, and mmu-miR-467b-5p) were screened and validated using quantitative real-time PCR. Furthermore, the GO analysis revealed that the identified DEMs were enriched in biological adhesion extracellular matrix, and growth factor binding, while the KEGG analysis suggested that the enriched DEMs were involved in ECM-receptor interaction, mTOR signaling pathway, MAPK signaling pathway, and AMPK signaling pathway. Our results may aid in elucidating the underlying mechanisms associated with DZN-induced hippocampal toxicity and provide valuable insights into the pathogenesis of neurotoxicity triggered by other organophosphorus pesticides.
研究领域:
神经毒理学
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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
MICROCHIMICA ACTA
·
2025
·Vol. 193
·期 1
·44
·
IF 5.3
Fan Yafeng,Jiao Baoping,Yu Zhongping,Zong Bingbing,Li Haiyan,Wu Xianzhen
A new kind of electrochemical biosensor was fabricated by modifying a glassy carbon electrode (GCE) with Ni-doped ZnO nanorods suspension for the sensitive and selective detection of miRNA-21. The electrode surface was coated with polydopamine (PDA), crosslinked with glutaraldehyde, and functionalized with DNA probes. Bovine serum albumin (BSA) was then used to block non-specific binding sites. Electrochemical analyses were adopted to systematically investigate the progress of the stepwise electrode modification and the hybridization. The electrochemical characterization indicated a gradual decrease in current response and an increase in charge-transfer resistance after each modification step, verifying the successful assembly of the sensing interface. Following optimization, the biosensor could detect concentrations as low as 21.30 fM with a dynamic linear range of 10 − 6 nM to 10 5 nM, good reproducibility, and selectivity to the mismatch and non-complementary sequences. Crucially, recovery experiments in spiked human serum samples gave satisfactory results, confirming the clinical potential of the system. In general, the Ni-doped ZnO nanorod-based biosensor provides sensitive, label-free, and low-cost detection of circulating miRNAs. Its modularity allows for simple conversion for detection of other nucleic acid-based biomarkers, implicating it as a useful diagnostic tool for early cancer diagnosis and point-of-care screening. Graphical abstract
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2024
·
IF 3.8
Luo Xianzhun,Dai Qingshan,Qiu Xia,Wang Dongmei,Li Yongxin
As biomarkers of cancer, the accurate and sensitive detection of microRNAs is of great significance. Therefore, we proposed a surface-enhanced Raman scattering (SERS)/electrochemical (EC) dual-mode nanosensor for sensitively detecting miRNA-141. The nanosensor uses Au@Ag nanowires as a novel SERS/EC sensing platform, which has the advantages of good biocompatibility, fast response, and high sensitivity. The dual-mode nanosensor can not only effectively overcome the problem of insufficient reliability of single signal, but also realize the amplification and stable output of the detection signal, to ensure the reliability and repeatability of miRNA detection. With this sensing strategy, the target miRNA-141 can be detected over a wide linear range (100 fM to 50 nM) (LOD of 18.4 fM for SERS and 16.0 fM for electrochemical methods). In addition, the process shows good selectivity and can distinguish miRNA-141 from other interfering miRNAs. The actual analysis of human serum samples also proves that our strategy has good reliability, repeatability, and has broad application prospects in the field of analysis and detection. Graphical Abstract
研究领域:
生物技术
·
纳米技术
·
分析化学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2024
·
IF 3.9
Jiawen Cui,Zhenda Liang,Yuhao Liu,Zhiyu Hao,You Tang,Li Zhou,Xiaohua Teng
Environmental endocrine disrupting chemical 4-tert-butylphenol (4-tBP), a widely-utilized surfactant in various industries, poses potential risks to aquatic organisms. Our previous sequencing results suggested that 4-tBP-induced common carp liver injury might be associated with Ca 2+ signaling and autophagy. However, the intricate involvement of these pathways in 4-tBP-induced cytotoxic mechanisms remained unexplored. To bridge these knowledge gaps, this study focused on epithelioma papulosum cyprini (EPC) cells, a significant cell type in fish biology. Initial observations showed that 4-tBP induced a dose-dependent perturbation in Ca 2+ levels. Further investigations, with siRNA and L-type Ca 2+ channel agonist (BAY K8644), identified L-type calcium channel gene CACNA1D as a critical regulator of 4-tBP-induced Ca 2+ overload. Predictive analysis using miRanda platform suggested a potential interaction between miR-363 and CACNA1D, which was subsequently verified through dual-luciferase reporter gene assays. We then established miR-363 mimic/inhibitor models, along with miR-363 and CACNA1D co-suppression models in EPC cells. Through TEM observation, immunofluorescence assay, Ca 2+ staining, and qRT-PCR analysis, we evaluated the role of miR-363/CACNA1D axis in modulating the effects of 4-tBP on Ca 2+ signaling and autophagy. Results showed that miR-363 inhibitor exacerbated 4-tBP-induced increase in CALM2, CAMKII, Calpain2, and p62 expression and also led to decrease in ATG5, ATG7, and LC3b expression. In contrast, miR-363 mimic notably alleviated these changes. Notably, siRNA CACNA1D effectively modulating miR-363 inhibitor's effect. Our study revealed that 4-tBP induced Ca 2+ overload and subsequent autophagy impairment via miR-363/CACNA1D axis. These findings illuminated a profound understanding of molecular mechanisms underlying 4-tBP-induced cytotoxicity and spotlighted a potential therapeutic target.
研究领域:
环境科学
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毒理学
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细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Yameng Li,Peilin Wang,Huan Wang,Zhenrun Li,Zihui Liang,Qiang Ma
MiRNA-214 can regulate the expression of their downstream target genes after post-transcriptional and are involved in the biological processes of triple negative breast cancer (TNBC). In this work, the small-sized luminescent Nb 2 C nanosheet-based whispering gallery mode-enhanced electrochemiluminescence (ECL) strategy was successfully constructed to detect miRNA-214 in TNBC. Firstly, we have synthesized small-sized luminescent Nb 2 C nanosheets from Nb 2 AlC MXene. The Nb 2 C nanosheets not only exhibited more stable chemical properties and reduced the defects of the large sheet structures, but also possessed the quantum confinement effect with the discrete energy level. As a result, the prepared small-sized Nb 2 C nanosheets had unique luminescent and electrochemical properties. Furthermore, in order to improve the ECL performance of Nb 2 C nanosheets, SiO 2 microspheres were self-assembled on the electrode surface by gas-liquid interface method to form whispering gallery mode structure. Because the light was continuously reflected at the interface of the microcavity in the whispering gallery mode, the ECL signal of Nb 2 C luminescent nanosheets was amplified largely. Finally, the whispering gallery mode-based ECL sensing platform was established. The results showed that the biosensor had a good linear correlation between the ECL intensity and the logarithm of concentration of miRNA-214 in the range of 10 fM to 100 nM with a limit of detection of 2.5 fM. The actual detection of miRNA-214 content in clinical TNBC tissue samples was realized successfully.
研究领域:
材料科学
·
分析化学
·
生物医学工程
·
癌症生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Mengxu Sun,Qianying Zhou,Jing Peng,Simin Liu,Jiaxin Luo,Lingling Bai,Wen-Jun Duan,Jin-Xiang Chen,Zong Dai,Jun Chen
As an important disease biomarker, the development of sensitive detection strategies for miRNA, especially intracellular miRNA imaging strategies, is helpful for early diagnosis of diseases, pathological research, and drug development. Hybridization chain reaction (HCR) is widely used for miRNA imaging analysis because of its high specificity and lack of biological enzymes. However, the classic HCR reaction exhibits linear amplification with low efficiency, limiting its use for the rapid analysis of trace miRNA in living cells. To address this problem, we proposed a toehold-mediated exponential HCR (TEHCR) to achieve highly sensitive and efficient imaging of miRNA in living cells using β-FeOOH nanoparticles as transfection vectors. The detection limit of TEHCR was as low as 92.7 fM, which was 8.8 × 103 times lower compared to traditional HCR, and it can effectively distinguish single-base mismatch with high specificity. The TEHCR can also effectively distinguish the different expression levels of miRNA in cancer cells and normal cells. Furthermore, TEHCR can be used to construct OR logic gates for dual miRNA analysis without the need for additional probes, demonstrating high flexibility. This method is expected to play an important role in clinical miRNA-related disease diagnosis and drug development as well as to promote the development of logic gates.
研究领域:
生物技术
·
纳米技术
·
分子生物学
·
癌症研究
·
诊断学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Jingyu Cui,Jiafang Piao,Houyu Han,Weipan Peng,Mengyao Lin,Dianming Zhou,Cheng Zhu,Xiaoqun Gong
Circulating microRNAs (miRNAs) have recently emerged as noninvasive disease biomarkers. Quantitative detection of circulating miRNAs could offer significant information for clinical diagnosis due to its significance in the development of biological processes. In response to the current challenges of circulating miRNA detection, we introduce a sensitive, selective, and versatile circulating miRNA detection strategy using terminal deoxynucleotidyl transferase (TdT)-catalyzed RNA-primed DNA polymerization (TCRDP) coupled with semiarbitrary qPCR (SAPCR). Semiarbitrary qPCR was first developed here to detect long fragment targets with only a short-known sequence or to detect a short fragment target after extension with terminal transferase. Besides, the subsequent results show that TdT has a preference for RNA, particularly for extending RNAs with purine-rich and unstructured ends. Consequently, utilizing this assay, we have successfully applied it to the quantitative analysis of circulating miR-122 in animal models, a sensitive and informative biomarker for drug-induced liver injury, and as low as 200 zmol of the target is detected with desirable specificity and sensitivity, indicating that the TCRDP-SAPCR can offer a promising platform for nucleic acids analysis.
研究领域:
分子生物学
·
临床诊断
·
生物技术
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Guohua Qi,Xingkang Diao,Yu Tian,Dan Sun,Yongdong Jin
Exosomal miRNA expression derived from tumor cells provides a valuable and promising noninvasive modality for the early diagnosis and assessment of the efficacy of cancer treatment. However, accurate detection and identification of miRNA within exosomes have been challenging due to its low abundance and the complexity and tedious extraction with large sample volumes in the separation process. Here, we developed an electrically activated nanoplatform for rapid and sensitive detection and identification of exosome miRNA, through triggering miRNA release by opening exosomes that were captured on the electrode surface using a slightly applied electric field (50 mV), and simultaneously detected them with surface-enhanced Raman spectroscopy (SERS) in situ. The method possessed superior specificity and sensitivity for exosomal miRNA detection, with a low detection concentration of 0.5 nM. The SERS sensor chips also showed a superior sensing performance of exosomal miRNA in complex body fluids such as urine and blood. We found that exosomal miRNA contents derived from tumor cells were significantly higher than those in normal cells, and importantly, the concentrations of exosomes secreted from three different cell lines were distinctly augmented after mild electrical stimulation (ES) treatment. Furthermore, the miRNA expression within exosomes was upregulated after the ES treatment of cells. The developed approach and SERS detection platform for exosomal miRNA are promising for noninvasive and precise screening, classification, and monitoring of cancer.
研究领域:
癌症生物学
·
纳米技术
·
生物医学工程
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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