Environmental Science-Nano
·
2022
·Vol. 9
·期 9
·3417-3426
·
IF 9.473
Fan Yang,Wei Wang,Mei Zhang,Wenxin Tao,Youwang Wang,Jiameng Shi,Yuedi Ding,Minhao Xie,Sai Zhang,Zhenqiang Fan,Kai Zhang
Since the emergence of coronavirus disease 2019 (COVID-19), this highly contagious disease has ravaged the world, cumulatively causing millions of deaths and huge economic losses. As the culprit of COVID-19, severe acute respiratory syndrome β-coronavirus 2 (SARS-CoV-2) is highly infectious and pathogenic, which has caused extreme panic worldwide. Early and rapid monitoring of SARS-CoV-2 has a significant role in suppressing the pandemic and reducing the virus's lethality. In our work, we prepared a self-enhanced ruthenium complex linked to zeolitic imidazole framework-8 (ZIF-8) and used it as an electrochemiluminescence (ECL) emitter. Additionally, a double-stranded specific nuclease (DSN)-assisted target RNA cycling with catalytic hairpin assembly (CHA) signal amplification technology was used to achieve the conversion of target RNA concentration to double-stranded DNA (dsDNA) output which significantly improved the detection sensitivity of target RNA under environmental conditions and in real human serum samples. In addition, we also combined the trans-cleavage property of CRISPR–Cas12a with the adsorption property of C3N4 on a ferrocene (Fc)-labeled DNA probe and obtained target RNA-dependent ECL signals. The reliable detection protocol achieved the transformation of SARS-CoV-2 RNA concentration to ECL responses, obtaining a limit of detection (LOD) of 0.67 fM with high specificity and reproducibility, which was of guiding significance for current detection methods of mutant SARS-CoV-2 and universal RNA.
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MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Shudong Chen,Chenglei Ren,Hui Zheng,Xianchun Sun,Jundi Dai
Background lncRNA HCP5 plays a cancer-promoting role in a variety of cancers. This study was the first to explore the mechanism of HCP5 in gastric carcinoma (GC). Material/Methods The differences in HCP5 between GC patients and healthy people were revealed in the TCGA database. The expression of HCP5 in GC tissues and adjacent tissues was compared by qRT-PCR. At the same time, the clinic pathological features of the patients were counted. Starbase and luciferase assay predicted and verified that miR-27b-3p is a targeted miRNA for HCP5. The expression of HCP5 and miR-27b-3p in various GC cells was detected by qRT-PCR. Cell viability and metastasis in different treatment groups were assessed by use of Cell Couting Kit-8 assay and clone formation assay, wound-healing assay, and transwell assay. Finally, expression of epithelial-mesenchymal transition (EMT)-associated markers was detected by Western blot. Results We found that HCP5 was overexpressed in GC tissues. Patients with higher expression of HCP5 had larger tumors, were more likely to have lymph node metastasis, and had higher TNM stage. HCP5 was overexpressed in GC cells, but this was reversed by miR-27b-3p. Silencing HCP5 inhibited GC cell viability and metastasis by downregulating Vimentin and N-cadherin and up-regulating E-cadherin, but this effect was partially reversed by miR-27b-3p inhibitor. Conclusions The effect of silencing HCP5 on repressing GC cells viability and metastasis by regulating EMT-associated markers can be partially reversed by miR-27b-3p inhibitor.
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Cell Death & Disease
·
2018
·Vol. 9
·期 9
·1-11
·
IF 5.638
Wang Yunchuan,Zheng Jianping,Han Yue,Zhang Yijie,Su Linlin,Hu Dahai,Fu Xiaobing
Junctional adhesion molecule-A (JAM-A) belongs to the immunoglobulin superfamily, it predominantly exists at the tight junctions of epithelial and endothelial cells. JAM-A is known to regulate leukocyte trans-endothelial migration, however, how it affects the proliferation and migration of keratinocytes, the two essential steps during wound healing, has less been explored. In this study, we showed that JAM-A was significantly expressed in normal skin epidermis. RNAi-mediated JAM-A knockdown remarkably promoted the proliferation and migration of keratinocytes. We also found that loss of JAM-A increased the protein levels of p -FAK, p -Erk1/2, and p -JNK; however, FAK inhibitor PF-562271 restrained the expression of p -FAK and p -Erk1/2 elevated by JAM-A RNAi, but not p -JNK, and also slowed down keratinocyte proliferation and migration. Finally, in a rat wound model we showed that absence of JAM-A significantly promoted the wound healing process, while the use of PF-562271 or Erk1/2 inhibitor PD98059 repressed those effects. These data collectively demonstrate that suppressing JAM-A expression could promote the proliferation and migration of keratinocytes and accelerate the healing process of rat skin wounds, potentially via FAK/Erk pathway, indicating that JAM-A might serve as a potential therapeutic target for the treatment of chronic refractory wounds.
研究领域:
分子生物学
·
细胞生物学
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伤口愈合研究
·
信号通路
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Qingyou Cai,Fanfan Wang,Jingying Ge,Zhiguo Xu,Mei Li,Hui Xu,Hua Wang
Herein, we reported the G-wire-based self-quenched fluorescence probe and its application in ultrasensitive microRNA (miRNA) detection by combining with target-activated isothermal cascade amplification. The terminal-single-fluorescein (FAM)-labeled G-rich oligonucletides self-assembled into G-wire nanostructures (G-wires) with K + and Mg 2+ . Thereafter, the G-wires brought terminal-labeled FAM into close proximity, as a result, the self-quenched signal probe formed. Besides, when there was the target miRNA, target-activated isothermal cascade amplification converted miRNA into the copious trigger DNA. After hybridization between trigger DNA and the self-quenched probe, the G-wires were splited and forced the apart of proximate FAM, and then the self-quenched probe displayed an “on” mechanism. Therefore, the approach gave a limit of detection (LOM) of 0.82 aM to miRNA-21 and could be implemented within a wide linear range of 2 aM to 2 nM. This approach was able to distinguish the single-mismatched miRNA-21, which was selective and sensitive in detecting human spiked serum samples.
研究领域:
分子生物学
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生物化学
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纳米技术
·
癌症诊断
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高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 48
·8492-8497
·
IF 1.915
Wenjun Ouyang,ZhenHua Liu,GuiFeng Zhang,Zheng Chen,Longhua Guo,Zhenyu Lin,Bin Qiu,Guonan Chen
MicroRNAs (miRNAs) have attracted enormous interest due to their involvement in complex regulatory functions and for being closely linked to some cancers. Thus, qualitative and quantitative detection of miRNAs has become an urgent necessity. In this study, we report an enzyme-free fluorescent biosensor for miRNA-21 detection based on MnO2 nanosheets and catalytic hairpin assembly amplification. Results showed that the detection limit for miRNA-21 was 0.33 nM (S/N = 3) and the linearity range was from 1 to 50 nM. Compared with traditional methods, such strategy is convenient, rapid, and low-cost and it can have a promising potential for miRNA detection in cancer.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
纳米技术
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高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 3
·1-9
·
IF 5.705
Wang Wei,Jayachandran Silambarasan,Li Mengru,Xu Shenghao,Luo Xiliang
An electrochemical biosensor for the detection of microRNA was prepared via chemical grafting of a Methylene Blue labeled reporter (MB-Rep) duplex onto a nanostructured surface that was obtained by electrodeposition of cobalt oxide and poly(o-phenylenediamine). This is followed by the attachment of hyaluronic acid and gold nanoclusters. In the presence of the target (microRNA), the probe-target duplex and the MB-Rep hairpin are formed. These will displace the labeled reporter from the sensor surface, and this results in a decrease of the amperometric signal for MB at a typical working voltage of −0.28 V (vs. Ag/AgCl). The electrode modified with hyaluronic acid possesses a large electroactive surface area and an excellent antifouling property. This makes it useful for ultrasensitive quantitation of microRNA even in complex biological media. The sensor has a linear response in the 100 f. to 0.1 μM microRNA concentration range, and a 33.3 f. detection limit. It was successfully applied to the determination of microRNA in cancer cells.
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研究领域:
生物化学
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电化学
·
纳米技术
·
癌症诊断
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JOURNAL OF SOLID STATE ELECTROCHEMISTRY
·
2014
·Vol. 18
·期 10
·2829-2835
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IF 2.234
Wang Mo,Yin Huanshun,Fu Zhengliang,Guo Yunlong,Wang Xinxu,Zhou Yunlei,Ai Shiyun
MicroRNAs (miRNAs), a class of small endogenous nonprotein-coding RNAs, regulate a wide range of biological processes, and their abnormal expressions are related to the growth and development of plants. Thus, a simple, rapid, and highly sensitive assay for miRNA detection is of great significance. In this work, a label-free and ultrasensitive assay for miRNA detection using protein cage nanoparticles has been developed. Apoferritin-encapsulated Cu nanoparticles (Cu-apoferritin) could be immobilized on the electrode through special reaction between amino and carboxyl. Hybridization event between the probe DNA and the target miRNA-159a is confirmed by electrochemical oxidation signal after Cu released into the detection buffer by adjusting the pH. This assay is highly selective and sensitive with a low detection limit of 3.5 fM. Moreover, the developed method can even discriminate single-base mismatched strand between the complementary targets. The effect of abscisic acid on the expression level of miRNA-159a in Arabidopsis thaliana seeds was also investigated.
研究领域:
植物学
·
遗传学
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纳米技术
·
电化学
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高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Weijie Li,Ruicong Yan,Yong Liu,Chuanchuan He,Xiaojuan Zhang,Yao Lu,Muhammad Waseem Khan,Chuanrui Xu,Tan Yang,Guangya Xiang
Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.
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Stem Cells International
·
2024
·Vol. 2024
·期 1
·7419270
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IF 3.8
Rui Zhai,Fumin Tai,Kexin Ding,Xin Tan,Hujie Li,Zhengyue Cao,Changhui Ge,Xiaofei Zheng,Hanjiang Fu
Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.
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BIOSENSORS & BIOELECTRONICS
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2022
·
IF 12.545
Min Yang,Hongyu Li,Xiangyang Li,Kunlun Huang,Wentao Xu,Longjiao Zhu
CircRNA, a group of circular, closed, single-stranded non-coding RNA, is an important biomarker for cancer diagnosis and prognosis. Sensitive and selective detection of circRNA can greatly facilitate the early diagnosis of human diseases. Herein, an isothermal amplification system is proposed based on dual-catalyzed hairpin self-assembly (CHA) and chameleon DNA templated silver nanoclusters (DNA-AgNCs) for the label-free ratiometric detection of circRNA. The upstream CHA1 could be specifically triggered by the analyte to form double-stranded DNA (dsDNA) products, leading to the red fluorescence of hairpin DNA-AgNCs decreased due to the destruction of the hairpin structure. The resulting dsDNA, with a trigger sequence, could then further activate downstream CHA2 to generate another dsDNA complex, which induced the other dark AgNCs to approach the G-rich sequence, thereby causing a dramatic increase in green fluorescence. Thus, by measuring the distinct variation in the ratios of green and red fluorescence intensities , the ratiometric system could be used to sensitively detect and visually distinguish the circRNA. In addition, the two-stage signal amplification in the CHA cycle endowed the detection method with ultra-sensitive detection performance, in which the detection limits for the RNA target were honed to 1 pM. Moreover, this novel method can be used as a general strategy to analyze different types of circRNA, thus showing its great potential for the detection of low abundant biomarkers in various clinical research studies.
研究领域:
生物化学
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分子生物学
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纳米技术
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癌症研究
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MOLECULAR THERAPY
·
2025
·
IF 12
Mengya Zhang,Xueguang Zhang,Chen Tan,Ting Jiang,Zheng Cao,Yufei Chen,Feng Qiao,Gelin Huang,Chaoye Ma,Huixia Li,Mei Ye,Lei Wang,Liandong Zuo,Jun Yu,Xiaofeng Li,Yunfang Zhang,Yue-Qiu Tan,Shuibin Lin,Wenming Xu,Hao Chen
Recent studies have highlighted RNA modifications as integral regulators of gene expression during spermatogenesis. Ribosomal RNAs (rRNAs) are the most abundant RNA in cells, while the function and clinical relevance of rRNA modifications in spermatogenesis remain poorly understood. Here, we identified 4 pathogenic heterozygous variants of METTL5 in 1,427 patients with male infertility characterized as oligoasthenoteratozoospermia (OAT). The pathogenic variants of METTL5 led to the significantly decreased expression level of METTL5. Null mutation of 18S rRNA methyltransferase Mettl5 led to male infertility attributed to OAT during spermiogenesis, presenting defects in both the sperm head and tail. Notwithstanding the absence of notable changes in global translation after Mettl5 loss, we observed a compromised translational efficiency of mRNAs encoding proteins crucial for spermiogenesis, including Gk2 , Akap4 , Fsip2 , Odf2 , and Pgk2 . Intriguingly, therapeutic interventions via intracytoplasmic sperm injection in OAT couples with these variants resulted in successful pregnancies. These insights not only identify METTL5-mediated 18S rRNA m 6 A modification as a novel genetic determinant for OAT but also offer a new target to the genetic counseling, clinical diagnosis, and potential treatment strategies for male infertility.
研究领域:
分子生物学
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遗传学
·
生殖医学
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RNA修饰
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发育生物学
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 6
·e70089
·
IF 1.7
Chunhua Liu,Changli Fu,Luping Tang,Jieqi Li,Jia Sun,Yuan Lu,Jie Pan,Ting Liu,Yongjun Li,Yonglin Wang,Yong Huang,Yueting Li,Meng Zhou
Polygonum orientale L. (PO) represents significant bioactivities in treating myocardial ischemia (MI); however, its underlying mechanisms remain unclear. This study aims to elucidate PO's potential mechanisms in MI using an integrated approach that combines UHPLC–Q-Exactive Orbitrap HRMS, network pharmacology, and RNA-sequencing (RNA-seq). Initially, the chemical constituents of PO were identified using UHPLC–Q-Exactive Orbitrap HRMS. Subsequently, network pharmacology, molecular docking, and RNA-seq were employed to screen potential active components of PO targeting MI and predict their molecular mechanisms. Then, the molecular mechanisms were verified using western blotting and ELISA in MI mice. A total of 45 components were identified from PO, with 14 potential active compounds interacting with 204 MI-related genes. The findings suggest that PO could alleviate heart damage. The RNA-seq results indicated 244 potential targets regulated by PO. Integrating RNA-seq and network pharmacology analyses revealed that the toll-like receptor signaling pathway plays an important role, alongside the PI3K-Akt. Notably, PO reduced the expression of TLR4 and TLR2 while increasing p-Akt and p-PI3K levels in MI mice, leading to decreased inflammatory cytokines and apoptosis-related proteins. This study provides initial evidence that PO inhibits the toll-like signaling pathway and activates PI3K–Akt signaling pathway to exert protective effects against MI.
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