Discovery Medicine
·
2024
·Vol. 36
·期 186
·1420-1429
·
IF 2
Shimaa Saad El-Din,Basma Emad Aboulhoda,Amira Hassouna,Marwa M Shakweer,Mansour A Alghamdi,Doha Essam,Mohamed Essam,Nawaf A AlRakaf,Hanaa M Elzahed,Asmaa Selmy,Dina Sabry,Dina M Mekawy
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 ( circYAP1 ) and microRNA-21 ( miRNA-21 ) in the rat knee joints. Methodology: Gene expression circYAP1 , miRNA-21 , toll-like receptor-7 ( TLR7 ), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. Results: Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level ( p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 ( p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( p < 0.05). Conclusion: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.
研究领域:
再生医学
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干细胞生物学
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分子生物学
·
骨科
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Ye Liu,Jiufeng Zhao,Xingrui Mu,Junyu Deng,Xingqian Wu,Wenjie He,Yiqiu Liu,Rifang Gu,Felicity Han,Xuqiang Nie
Ethnopharmacological relevance Centella asiatica (L.) Urban is an ethnobotanical herb. The main bioactive components of Centella asiatica are pentacyclic triterpenoid glycosides , namely asiaticoside and hydroxyasiaticoside. Asiaticoside possess a diverse array of pharmacological properties, such as wound-healing, anti-inflammatory, antioxidant, anti-allergic, antidepressant, anxiolytic, anti-fibrotic, antibacterial, anti-arthritic, anti-tumor, and immunomodulatory activities. Aim of the study The purpose of this investigation is to explore potential therapeutic interventions for the delayed healing of wounds in diabetic patients (DW) facilitated by Asiaticoside-Nitric Oxide. To clarify the key molecular mechanism of miRNA-21-5p in DW wound repair and to deepen the understanding of DW disease pathogenesis. Materials and methods Firstly, miRNA microarray technology, bioinformatics, and RT-qPCR were used to analyze DW patients' and normal controls' skin tissue samples. Secondly, in order to investigate the role of miRNA-21-5p, a hyperglycemic model was established using HaCaT cells. Overexpressing as well as interfering HaCaT cell lines were constructed by lentiviral infection to further explore the proliferative and migratory effects of Asiaticoside-Nitric Oxide. The next step was to search for potential target genes of miRNA-21-5p and verify them with dual-luciferase reporter assay. Finally, the expression levels of target genes and proteins were detected through the utilization of RT-qPCR and Western blotting under the influence of Asiaticoside-Nitric Oxide. Results A library of miRNAs and target genes expressed explicitly in DW patients and rats was established. The study confirmed the upregulation of miRNA-21-5p in DW patients and identified its involvement in signaling pathways related to chronic ulcer wound repair. Overexpression of LV-miRNA-21-5p significantly promoted cell proliferation , while treatments of Asiaticoside-Low dose (AC-L) and Asiaticoside-Medium dose (AC-M) enhanced proliferation and migration, particularly when combined with nitroprusside (SNP). Further analysis revealed potential target genes of miRNA-21-5p, such as TGF-β1, SMAD7, and TIMP3. Their interaction with miRNA-21-5p was confirmed through dual luciferase assays. The study found that anti-DW drugs increased the expression of TGF-β1 and SMAD7 while inhibiting TIMP3 expression in a high-glucose environment. Conclusions The research concluded that miRNA-21-5p plays a crucial role in the delayed healing of diabetic wounds, and that the combination treatment of AC + SNP shows promise in promoting wound healing in DW rats. Target genes, including TGF-β1, SMAD7, and TIMP3, may contribute to the regulatory mechanisms involved in diabetic wound healing. These findings provide valuable insights for developing novel therapeutic approaches for DW.
研究领域:
药理学
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分子生物学
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糖尿病研究
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伤口愈合
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民族药理学
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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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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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PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Chenxu Peng,Mingyu Leng,Yongguang Gao,Qiumei Feng,Xiangmin Miao
In situ monitoring of intracellular microRNAs (miRNAs) often encounters the challenges of surrounding complexity, coexistence of precursor miRNAs (pre-miRNAs) and the degradation of biological enzyme in living cells. Here, we designed a novel probe encapsulated DNA tetrahedral molecular sieve (DTMS) to realize the size-selective detection of intracellular miRNA 21 that can avoid the interference of pre-miRNAs. In such strategy, quencher (BHQ-1) labeled probe DNA (S6-BHQ 1) was introduced into the inner cavity of fluorophore (FAM) labeled DNA tetrahedral scaffolds (DTS) to prepare DTMS, making the FAM and BHQ-1 closely proximate, and resulting the sensor in a "signal-off" state. In the presence of miRNA 21, strand displacement reaction happened to form more stable DNA double-stranded structure, accompanied by the release of S6-BHQ 1 from the inner cavity of DTMS, making the sensor in a "signal-on" state. The DTMS based sensing platform can then realized the size-selective detection of miRNA 21 with a detection limit of 3.6 pM. Relying on the mechanical rigidity of DTS and the encapsulation of DNA probe using DTMS, such proposed method achieved preferable reproducibility and storage stability. Moreover, this sensing system exhibited good performance for monitoring the change of intracellular miRNA 21 level during the treatment with miRNA-related drugs, demonstrating great potential for biological studies and accurate disease diagnosis.
研究领域:
分子生物学
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生物技术
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纳米技术
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细胞生物学
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分析化学
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医学诊断
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DOI
PubMed
高影响因子
ANALYST
·
2023
·Vol. 148
·期 9
·2180-2188
·
IF 4.2
Mengyao Li,Tingting Zhang,Yuzhong Zhang
In this study, an ultrasensitive electrochemical miRNA-21 biosensor is described. Manganese dioxide-gold nanoparticle (MnO2-Au NP) nanoconjugates were employed as sensing base materials, miRNA-21 was selected as a model analyte, and hybridization chain reaction (HCR) was employed to form long DNA concatemers using two different oligonucleotides with a complementary sequence. Thus, lots of biotin were loaded on DNA concatemers and one of them was labelled with biotin at its 3′ terminal. The biosensor was designed as follows: a sulfhydryl-hairpin probe (HP) was first dropped on the surface of the glassy carbon electrode (GCE) modified with MnO2-Au NP nanoconjugates (HP/MnO2-AuNPs/GCE). After it was treated with MCH, the modified electrode was hybridized with miRNA-21, resulting in the loop of HP being opened to form a vertical structure. Subsequently, the modified electrode (miRNA-21/HP/MCH/MnO2-AuNPs/GCE) was incubated with DNA concatemers to form a sandwich structure of HP-miRNA-21-DNA concatemers on the modified electrode surface. Finally, the streptavidin-HRP conjugates were linked to the sandwich structure by specific recognition interaction between biotin and avidin. Differential pulse voltammetry (DPV) was used to measure the electrochemical response of the biosensor in the phosphate-buffered solution (0.10 M PBS, pH 7.0) containing 2.0 mM hydroquinone (HQ) and 1.8 mM H2O2. As a result, a larger reductive signal was obtained at a potential of −0.17 V (vs. SCE). Various experimental conditions were optimized, including solution pH, incubation time, and the amount of DNA concatemers. Under optimal conditions, the biosensor showed good sensing performance, such as a wide linear response range (0.1 fM and 100 nM) and low detection limit (0.063 fM, at S/N = 3). Meanwhile, the biosensor can discriminate single base matched miRNA-21, indicating that the biosensor had good selectivity.
研究领域:
分析化学
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生物化学
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纳米技术
·
分子生物学
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PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2022
·Vol. 414
·期 14
·4079-4088
·
IF 4.478
Xu Wei,Zhang Yu,Chen Hao,Dong Jinhua,Khan Ranjha,Shen Jianjun,Liu Honglin
Here, we developed a surface-enhanced Raman scattering (SERS) sensor based on functionalized Au@Ag core–shell nanorods (Au@Ag NRs) and cascade DNAzyme amplifier (CSA) for sensitive and accurate determination of microRNA-21 (miRNA-21). The as-prepared SERS nanoprobes were composed of a thiol-modification hairpin probe (HP2)–functionalized Au@Ag NRs and hairpin DNAzyme (HP1-Dz). Compared with original gold nanorods, the silver shell caused an enhancement of plasmonic properties, resulting in a significant enhancement of Raman signals. In the presence of target miRNAs, the hairpin construction of HP1-Dz changed due to DNA/RNA hybridization; subsequently, the DNAzyme-catalyzed cleaving process changed, and the Raman signals of the SERS nanoprobes gradually “turned off” with time elapse because of the dissociation of the Raman reporter from the surface of Au@Ag NRs. Hence, based on this principle, the proposed SERS sensor exhibited good linearity in the range 0.5 fM to 10 nM for miRNA-21 detection with a detection limit (LOD) of 0.5 fM. The proposed SERS platform has potential application in quantitative and precise detection of miRNA-21 in human serum. Graphical abstract
研究领域:
纳米技术
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分析化学
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生物传感
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分子生物学
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生物医学工程
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 24
·10907-10913
·
IF 3.591
Yanfang Cui,Jing Zheng,Wei Zhuang,Haiwang Wang
A novel surface-enhanced Raman scattering (SERS) platform has been developed for the highly sensitive detection of miRNA-21 by target activation depending on exonuclease-assisted signal amplification with a plasmon coupling phenomenon. In this system, a Raman dye-modified gold nanoparticle (AuNP) substrate can be covalently linked by the thiolated DNA track and DNA walker, which combine the protection probe at the 3′ terminal end to prevent reaction with the DNA track. In the presence of miRNA-21, it will combine the protect probe to the DNA walker depending on more complementary base pairing and release the DNA walker, which will combine with the adjacent DNA track. Depending on the exonuclease III (exo III) cleavage, the DNA walker can walk along the surface of AuNPs and produce the self-assembled hot spots between AuNPs, allowing a homogenous detection of the miRNA-21 with high sensitivity and reproducibility. Under optimized experimental conditions, the platform detected miRNA-21 with a wide range from 10 pM to 1.0 × 105 pM and displayed very low detection limit (4.0 pM). Hence, the novel strategy will become a promising tool for the SERS assay of miRNA-21 with high sensitivity and repeatability. Furthermore, this platform also owns great potential for cancer typing and clinical diagnostics.
研究领域:
分析化学
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纳米技术
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生物医学工程
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分子生物学
·
癌症研究
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产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Mengxin Zhang,Yingyu Zhang,Xianwei Zhang,Kangbo Liu,Lifeng Li,Zhidan Yu,Jingya Yuan,Wancun Zhang
Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.
研究领域:
生物化学
·
分子生物学
·
医学影像学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2021
·
IF 7.991
Xiqi Ma,Xiaojuan Wang,Cai Liu,Baosheng Ge,Hua He,Qi Dai,Zhixiong Zhang,Jinyi Yu,Werner M. Nau,Fang Huang
Compared with primary and local tumor, metastasis is more difficult to resect completely and remain the leading cause of death associated with solid tumors. It is therefore pressing to develop effective strategies to prevent and suppress tumor metastasis in its early stages. Heparanase overexpression is significantly associated with increased malignancy and metastasis. Here, we develop a novel heparanase degradable heparin-based microcarrier, HBMA, for specific staining, targeting, and inhibiting tumor cells with high metastatic potential. HBMA is fabricated through self-assembling of three components, positively charged fluorescent gold nanoclusters (KG-AuNCs), heparin polymers (HP), and antisense miRNA-21 oligonucleotides (AM-21), with each component playing multiple roles. Results of confocal microscopy and flow cytometry show that this agent has an excellent capability to label metastatic tumor cells with high selectivity. On the therapeutic side, the results of cell viability assay, wound healing assay, and plate colony formation assay verify that HBMA induces a significant inhibition effect towards the proliferation and migration of the selectively target tumor cells. The heparanase responsive AM-21 delivery, the specific staining, and the efficient tumor cell activity suppression highlight HBMA as a promising cancer theranostic agent to prevent tumor metastasis.
研究领域:
肿瘤学
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分子生物学
·
纳米医学
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DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2026
·
IF 6.1
Dan Qin,Shijin Zhou,Davaasuren Tsendjav,Jing Li,Jinming Kong
Background The early and accurate detection of miRNA-21 is of great significance for both lung cancer diagnosis and livestock health monitoring, given its conserved sequence across mammals. Herein, we report an enzyme-free electrochemical biosensor based on surface-initiated ring-opening metathesis polymerization (ROMP) for the ultrasensitive detection of miRNA-21. A thiolated peptide nucleic acid (PNA) probe was immobilized on a gold electrode to capture the target. The formed PNA–RNA hybrid duplex provided a high-density phosphate backbone that served as a coordination anchor for Zr(IV) ions, enabling directional immobilization of acrylic acid monomers via Zr–O–P/Zr–O–C bridges. Subsequent addition of a water-soluble ruthenium catalyst (AquaMet) initiated in situ ROMP of cyclopentenyl ferrocene (CFc) monomers, converting a single hybridization event into long polymer chains densely decorated with electroactive ferrocene units for substantial signal amplification. Results Under optimized conditions, the biosensor exhibited a wide linear range from 0.1 fM to 0.1 nM, with an ultralow detection limit of 67 aM. It showed excellent selectivity against single-base mismatches, as well as good reproducibility and storage stability. Importantly, the sensor maintained satisfactory recovery rates in diluted human serum and demonstrated strong anti-interference capability in complex matrices. Significance Owing to the sequence conservation of miRNA-21 across mammals and the mild, enzyme-free nature of the ROMP strategy, this platform holds great potential for both clinical lung cancer screening and on-site health monitoring in livestock and poultry.
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高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Shijin Zhou,Zhidan Tian,Qinyuan Xu,Jinming Kong,Xueji Zhang
Orthogonal dual-stage ROMP cascade enables ultrasensitive miRNA-21 detection. • Scaffold construction and signal amplification are decoupled. • The sensor detects miRNA-21 with a detection limit of 2.24 aM. • High selectivity and reliable performance in complex serum matrices. Traditional ring-opening metathesis polymerization (ROMP)-based biosensors typically couple scaffold construction and signal amplification within a single polymerization step, which limits the independent optimization of mechanical stability and electrochemical performance. This study developed an orthogonal two-stage ROMP cascade amplification strategy that successfully decoupled these two processes. Target-specific hybridization first triggers Zr 4+ coordination, initiating surface-mediated metal-catalyzed ROMP to construct a dense polynorbornene scaffold bearing cyclic anhydride side chains. Subsequently, metal-free ROMP driven by visible light grafts high-density ferrocene monomers onto the pre-assembled scaffold, forming electroactive bottlebrush polymers. This biosensor achieves a detection limit for miRNA-21 as low as 2.24 aM, with a linear range from 10 aM to 1 nM, and exhibits excellent selectivity against mismatched RNA sequences, as well as reliable detection performance in complex serum matrices. The orthogonal cascade strategy proposed in this study provides a modular and versatile new platform for the ultrasensitive detection of low-abundance biomarkers. Download: Download high-res image (116KB) Download: Download full-size image
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高影响因子
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