Journal of Stroke & Cerebrovascular Diseases
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2021
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IF 2.136
Yue Shu,Juan Huang,Meng Gao,Shengwei Gan,Shujuan Zhu,Shiye Xu,Zhengyu Yang,Yuhui Liao,Weitian Lu
Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis , neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema , and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment .
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SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Hui Kong,Wei Zhang,Jia Yao,Chao Li,Renfei Lu,Zhen Guo,Jinze Li,Chuanyu Li,Yingxue Li,Chiyu Zhang,Lianqun Zhou
Development of a simple, sensitive and specific method for HIV-1 assay is demanded. In some emergency situations, a portable reverse transcription loop-mediated isothermal amplification (RT-LAMP) platform is necessary. A novel hydrogen ion-selective RT-LAMP (H + -RT-LAMP) sensor was developed for highly sensitive HIV-1 using hydrogen ion concentration as a signal producing compound. The H + -RT-LAMP sensor was based on screen-printed with carbon-doped graphene conductive layer, carbon nanotubes (CNTs) solid electrolyte layer, and reference electrode KCl functional layer, which provided superior electrical signals, high sensitivity and stability for HIV-1 detection. The rate of hydrogen ion production was related to the viral load (VL) during the amplification of HIV-1. The sensitive HIV-1 RNA detection range was achieved from 0 copies/μL to 10 5 copies/μL. The proposed H + -RT-LAMP sensor was applied to detect HIV-1 RNA in real human serum. 57 samples were detected and satisfactory results were obtained. Compared with commercial instruments, the detection results of H + -RT-LAMP sensor demonstrated a perfect concordance rate of 96.5 %, and the limit of detection (LOD) for the clinical samples was 10 copies per tube. Time to get the result is from 10 min to 25 min. Therefore, the proposed H + -RT-LAMP sensor was particularly suitable as a point-of-care device for the on-site detection of HIV-1.
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JOURNAL OF HAZARDOUS MATERIALS
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2021
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IF 10.588
Danting Wang,Xuedong Wang,Haishan Huang,Huili Wang
Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes ( mbpa , mef2d , u2af2b and matn3b ). Histopathological injury, phenotypic malformation, abnormal locomotor behavior and changes in neuromarkers all confirmed the biological functions of CELF2 in zebrafish brain. These findings demonstrate that TCS might regulate some of the AS events of nerve-related genes through upregulating the expression of CELF2. Thus, CELF2 may serve as a target for the prevention, diagnosis and treatment of contaminant-induced neurological diseases.
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RSC Advances
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2019
·Vol. 9
·期 70
·41088-41098
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IF 3.049
Danqi Li,Da Liu,Dandan Yue,Pinyi Gao,Cheng Du,Xuegui Liu,Lixin Zhang
Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. Bupleurum chinense DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both in vitro and in vivo experiments. Saikosaponin compounds are the characteristic constituent of B. chinense, which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of B. chinense. In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3′′,6′′-O-diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6′′-O-acetylsaikosaponin-b1 (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of B. chinense against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, etc. More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.
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ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Shuofeng Li,Fangfang Wang,Chenhuan Wang,Lin Hao,Ningzhao Shang,Pengbo Zhang,Yawen Zhang,Nuo Xiao,Yaai Kang,Jin Liu,Shutao Gao,Chun Wang,Zhi Wang,Qiuhua Wu
Single-atom nanozyme (SAZ) with peroxidase-like activity has attracted great attention in point-of-care (POC) diagnostic, but the use of unstable H 2 O 2 in peroxidase catalytic reactions often leads to low detection accuracy. Thus, developing SAZ with high oxidase (OD)-like activity to construct RNA sensing systems independent of H 2 O 2 is imperative for improving accuracy. Herein, a novel strategy to fabricate boron-nitrogen co-doped zinc SAZ (ZnBNC-SAZ) with excellent OD-like activity by carbonizing Zn based zeolitic boron imidazolate frameworks is reported. The electron deficient B in imidazolate ligand can form Zn─N─B bond in situ during high temperature pyrolysis, which can regulate the electronic structure of Zn and further upshift the d-band center of Zn to improve the OD-like activity. With ZnBNC-SAZ as signal generator, a new method for sensitive RNA detection is developed by combining CRISPR/ cas13 system with terminal deoxynucleotidyl transferase-induced DNA extension reaction. The limits of detection for RNAs are as low as 20 aM. The proposed biosensor is adaptable to a lateral-flow-based readout and is universally applicable for sensing various RNAs by programming the guide RNA. Importantly, the proposed biosensor can monitor the cellular differentiation and identify patients with cervical carcinoma, showing great potential for application in facile POC diagnosis.
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY
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2016
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IF 2.822
Ting Song,Xilin Guo,Xuemei Li,Shusheng Zhang
A label-free electrochemical biosensor for ultrasensitive let-7d RNA detection was developed based on nicking endonuclease (NEase) assisted template enhanced hybridization process (TEHP) and rolling circle amplification (RCA) induced formation of G-quadruplex–hemin complexes. The hairpin probe (H1) was immobilized on the gold electrode through a strong Au S bond. With the help of assistant DNA , the introduction of target let-7d RNA forms the nicking site for the NEase, which cleaves the hairpin probe and releases the target RNA. Further addition of another hairpin probe (H2) initiated the next two cascaded recycling process. The cleaved fragment acted as primer to activate RCA reaction, generating product containing hundreds of hemin aptamer and G-quadruplex–hemin complex can be formed with the help of K + and hemin to give an electrochemical response. The newly designed protocol provides an ultrasensitive electrochemical detection of let-7d RNA down to the 0.42 fM level, and can discriminate target RNA from the let-7 family, holding a great potential for early diagnosis in gene-related diseases.
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DRUG DELIVERY
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2017
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IF 6.402
Chen-Lin Feng,Yan-Xing Han,Hui-Hui Guo,Xiao-Lei Ma,Zhi-Qiang Wang,Lu-Lu Wang,Wen-Sheng Zheng,Jian-Dong Jiang
Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self-assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex. In vitro physiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle at G0/G1 phase and suppression of cancer cell proliferation as well as colony formation. Furthermore, in vivo distribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, following in situ application. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC.
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TALANTA
·
2024
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IF 5.6
Qiang Tang,Xiaoling Huang,Guangxing Liu,Hongran Huang,Jiayi Zhang,Jihua Wei,Yuanxun Gong,Qianli Tang,Kai Zhang,Xianjiu Liao
This study introduces a novel electrochemical biosensor for detecting Matrix Metalloproteinase-2 (MMP-2), a key biomarker in cancer diagnostics and tissue remodeling. The biosensor is based on a dual-amplification strategy utilizing T7 RNA polymerase isothermal amplification and CRISPR-Cas12a technology. The principle involves the release of a DNA template in the presence of MMP-2, leading to RNA synthesis by T7 RNA polymerase. This RNA activates CRISPR-Cas12a, which cleaves a DNA probe on the electrode surface, resulting in a measurable electrochemical signal.The biosensor demonstrated exceptional sensitivity, with a detection limit of 2.62 fM for MMP-2. This high sensitivity was achieved through the combination of transcriptional amplification and the collateral cleavage activity of CRISPR-Cas12a, which amplifies the signal. The sensor was able to detect MMP-2 across a wide dynamic range from 2 fM to 1 nM, showing a strong linear correlation between MMP-2 concentration and the electrochemical signal. In practical applications, the biosensor accurately detected elevated levels of MMP-2 in cell culture supernatants from HepG2 liver cancer cells, distinguishing them from normal LO2 liver cells. The use of an MMP-2 inhibitor confirmed the specificity of the detection. These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.
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Cancer Communications
·
2024
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IF 20.1
Wei Mu,Pengfei Gu,Huating Li,Jinjin Zhou,Yulun Jian,Weiping Jia,Yang Ge
Background Benzo[a]pyrene (B[a]P), a carcinogen pollutant produced by combustion processes, is present in the western diet with grilled meats. Chronic exposure of B[a]P in hepatocellular carcinoma (HCC) cells promotes metastasis rather than primary proliferation, implying an unknown mechanism of B[a]P-induced malignancy. Given that exosomes carry bioactive molecules to distant sites, we investigated whether and how exosomes mediate cancer-stroma communications for a toxicologically associated microenvironment. Method Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells (7404-100Bap Exo) at an environmental relevant dose (100 nmol/L). Lung pre-education animal model was prepared via injection of exosomes and cytokines. The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array. HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis. Profile of B[a]P-exposed exosomes were determined by ceRNA microarray. Interactions between circular RNA (circRNA) and microRNAs (miRNAs) were detected using RNA pull-down in target lung fibroblasts. Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the “on-off” interaction of circRNA-miRNA pairs. We further developed an adeno-associated virus inhalation model to examine mRNA expression specific in lung, thereby exploring the mRNA targets of B[a]P induced circRNA-miRNA cascade. Results Lung fibroblasts exert activation phenotypes, including focal adhesion and motility were altered by 7404-100Bap Exo. In the exosome-educated in vivo model, fibrosis factors and pro-inflammatory molecules of are up-regulated when injected with exosomes. Compared to non-exposed 7404 cells, circ_0011496 was up-regulated following B[a]P treatment and was mainly packaged into 7404-100Bap Exo. Exosomal circ_0011496 were delivered and competitively bound to miR-486-5p in recipient fibroblasts. The down-regulation of miR-486-5p converted fibroblast to cancer-associated fibroblast via regulating the downstream of Twinfilin-1 (TWF1) and matrix metalloproteinase-9 (MMP9) cascade. Additionally, increased TWF1, specifically in exosomal circ_0011496 educated lungs, could promote cancer-stroma crosstalk via activating vascular endothelial growth factor (VEGF). These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion, as a consequence of a pre-metastatic niche formation. Conclusion We demonstrated that B[a]P-induced tumor exosomes can deliver circ_0011496 to activate miR-486-5p/TWF1/MMP9 cascade in the lung fibroblasts, generating a feedback loop that promoted HCC metastasis.
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RSC Advances
·
2024
·Vol. 14
·期 45
·32883-32892
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IF 3.9
Xuehui Pang,Rui Liu,Xiaoyi Lv,Wenjun Lu,Lebin Sun,Qiuyan Wang,Zhen Li,Qing Kang,Jiandong Xie,Yingxin Pang,Feimeng Zhou
A photoelectrochemical (PEC) sensor based on the poly-2,2,5,2-terthiophene (pTTh)/Cu2O heterojunction was constructed and applied for the detection of long non-coding RNA (lncRNA) TROJAN, a biomarker of triple-negative breast cancer. Cu2O and pTTh were electrodeposited in situ and sequentially onto an indium tin oxide substrate. The bandgap of the resultant type II heterojunction was measured spectroscopically and the morphology was found to effectively separate photogenerated holes from electrons. A photocurrent density as high as 250 μA cm−2 was attained, which is about three times higher than those of only pTTh or Cu2O. Owing to the close contact between pTTh and Cu2O, this PEC sensor is highly stable. Oligonucleotide probes for lncRNA can be cross-linked to carboxyl moieties of mercaptopropionic acid molecules adsorbed on pTTh/Cu2O. The desirable band structure and the high density of probe molecules collectively yielded a linear range of 0.1–10 000 pM. Our PEC sensor has been demonstrated to be amenable for detection of lncRNA markers with excellent analytical performance.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
De Bai,Haowei Chen,Nanxi Xiang,Chunqiao Zhang,Zhenyuan Wang,Jichuan Zhang,Chengyu Wu,Fang Wang,Jiaheng Zhang
Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.
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ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Mimi Li,Lina Wang,Yue Hu,Yi Liu,Shuang Xu,Kexing Peng,Chenghong Li,Hui Huang,Lichao Fang,Lulu Li,Huamin Liu,Xiaolong Wang,Junsong Zheng
Sensitive and efficient detection of RNA methylation sites is considered an integral part of epigenetic assessment. Contrary to previous studies on the detection of RNA m5C or m6A methylation alone, this study innovatively designed a biosensor capable of detecting RNA m5C or m6A methylation at the same time. Substances with specific electrochemical reactions such as ferrocene (FC) or methylene blue (MB) were modified onto the hairpin probe. When the hairpin probe was activated under specific conditions, it triggered a dendritic nonlinear hybridization chain reaction (HCR), which resulted in signal amplification. Gold (Au) and iron tetraoxide (Fe 3 O 4 ) composite nanomaterials were employed as the linking materials: the carboxylated ends of Fe 3 O 4 were connected to an antibody that specifically recognizes the m5C and m6A methylation sites, while Au nanoparticle ends adhering to the carboxylated Fe 3 O 4 surface are connected to the HCR enhanced signal amplifier. The m5C antibody was linked to Fc-containing HCR amplification products by this material, and similarly, the m6A antibody was linked to MB-containing amplifiers. Thus, the dandelion complex, a multifunctional body with methyl recognition and signal amplification, was formed. The capture probe immobilized on the surface of the gold electrode by Au–S recognized the target RNA sequence by base complementary pairing. Upon addition of the dandelion complex, due to its multi-functionality, the amplified signals were carried to the electrode by the antigen-antibody recognition mechanism, generating a current signal. The positions and heights of the current signal peaks enabled rapid determination of target RNA methyl modification sites and their abundance. The detection limits of this biosensor for RNA m5C and m6A were 4.68 × 10 −16 M and 1.10 × 10 −15 M, respectively, and the linear range was from 10 −15 mol/L to 10 −8 mol/L. The sensor developed in this study has the advantages of cost-effectiveness, ease of fabrication, and fast response time, and has the potential to be promoted for RNA methylation detection.
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