ORCID Profile
0000-0002-9930-8878
Current Organisations
E O Lawrence Berkeley National Laboratory
,
Minjiang University
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Publisher: Wiley
Date: 09-07-2020
Publisher: Elsevier BV
Date: 09-2017
Publisher: Ubiquity Press, Ltd.
Date: 18-03-2021
DOI: 10.5334/DSJ-2021-011
Publisher: MDPI AG
Date: 03-11-2022
DOI: 10.3390/BIOM12111623
Abstract: Doxorubicin is the most frequently used chemotherapeutic agent for the treatment of hepatocellular carcinoma. However, one major obstacle to the effective management of liver cancer is the drug resistance derived from the cancer stem cells. Herein, we employed a CD133 aptamer for targeted delivery of doxorubicin into liver cancer stem cells to overcome chemoresistance. Furthermore, we explored the efficacy of autophagy inhibition to sensitize liver cancer stem cells to the treatment of CD133 aptamer-doxorubicin conjugates based on the previous observation that doxorubicin contributes to the survival of liver cancer stem cells by activating autophagy. The kinetics and thermodynamics of aptamer-doxorubicin binding, autophagy induction, cell apoptosis, and self-renewal of liver cancer stem cells were studied using isothermal titration calorimetry, Western blot analysis, annexin V assay, and tumorsphere formation assay. The aptamer-cell binding andintracellular accumulation of doxorubicin were quantified via flow cytometry. CD133 aptamer-guided delivery of doxorubicin resulted in a higher doxorubicin concentration in the liver cancer stem cells. The combinatorial treatment strategy of CD133 aptamer-doxorubicin conjugates and an autophagy inhibitor led to an over 10-fold higher elimination of liver cancer stem cells than that of free doxorubicin in vitro. Future exploration of cancer stem cell-targeted delivery of doxorubicin in conjunction with autophagy inhibition in vivo may well lead to improved outcomes in the treatment of hepatocellular carcinoma.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.TALANTA.2022.123997
Abstract: The microRNAs (miRNAs) play a critical role in many biological processes and are essential biomarkers for diagnosing disease. However, the sensitive and specific quantification of microRNAs (miRNAs) expression in living cells still faces a huge challenge. Our study designed a multifunctional linear DNA nanostructure (MLN) as a carrier of molecular beacons (MB-21) for detecting and intracellular imaging miRNA-21. The MLN-MB consists of three parts: aptamer, MLN, and MB-21. The aptamer (AS1411) could media MLN-MB enter live cells without additional transfection reagents. Once inside the cells, the intracellular miRNA-21 could hybridize the MB-21s, resulting in significantly enhanced fluorescence signals. The whole process was enzyme-free, autonomous, and continuous, which avoided the necessity of adding external fuel strands or enzymes. We demonstrated that the MLN-MB could be used to screen the miRNA-21 with a detection limit of 320 pM in a short time (10 min) and show high specificity toward miRNA-21 against other miRNAs. Moreover, the proposed MLN-MB could detect the miRNA-21 in complex matrixes stably. With its outstanding stability, dual recognition, and biocompatibility, MLN-MB is capable of delivering into living cells to identify specific cancer cells. Therefore, our sensing approach, with high sensitivity, specificity, and simplicity advantages, holds great potential for early cancer diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 17-04-2018
DOI: 10.1038/S41467-018-03861-1
Abstract: Ammonia-oxidising archaea (AOA) are ubiquitous and abundant in nature and play a major role in nitrogen cycling. AOA have been studied intensively based on the amoA gene (encoding ammonia monooxygenase subunit A), making it the most sequenced functional marker gene. Here, based on extensive phylogenetic and meta-data analyses of 33,378 curated archaeal amoA sequences, we define a highly resolved taxonomy and uncover global environmental patterns that challenge many earlier generalisations. Particularly, we show: (i) the global frequency of AOA is extremely uneven, with few clades dominating AOA ersity in most ecosystems (ii) characterised AOA do not represent most predominant clades in nature, including soils and oceans (iii) the functional role of the most prevalent environmental AOA clade remains unclear and (iv) AOA harbour molecular signatures that possibly reflect phenotypic traits. Our work synthesises information from a decade of research and provides the first integrative framework to study AOA in a global context.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.TALANTA.2018.07.090
Abstract: Herein, DNA nanostructures were prepared via a palindromic padlock probe-based rolling circle lification (called P-RCA) and then employed to implement the sensitive and specific detection of let-7a miRNA extracted from cancer cells without chemical modification. The presence of target let-7a miRNA as a polymerization primer can trigger the P-RCA process, generating a long tandemly repetitive DNA strand. The resulting products can fold into nanostructures via self-hybridization of palindromic regions and possess numerous double-stranded fragments. In this case, the strong fluorescent signal is detected upon exposure to SYBR Green I. As a result, in homogeneous solution, target miRNA can be detected down to 6.4 pM with a wide dynamic range. A high specificity was demonstrated by the excellent discrimination between let-7 miRNA family members, while the applicability of this sensing system in complex biological environments was confirmed by the analysis of target miRNAs extracted from HeLa cells. It should be noted that increasing numbers of palindromic fragments in padlock probe further increases signal lification efficiency. The experimental results indicate that the newly proposed P-RCA DNA nanostructures have potential to become a promising analytical platform in biomedical research and clinical diagnosis for the miRNA detection with high sensitivity and good specificity.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.ACA.2018.10.004
Abstract: MicroRNAs (miRNAs) play an important role in the regulation of various biological processes and have been used as potential biomarkers for biomedical research and clinical diagnosis. Here, nicking-mediated rolling circle lification (N-RCA)/symmetric isothermal circular strand-displacement lification (S-SDA)-integrated combined cascade lification (rs-CCA) was proposed for let-7a miRNA detection. Via introducing a palindromic fragment-integrated recognition sites for nicking endonuclease Nt.AlWI into the padlock probe, the hybridization of target miRNA can induce N-RCA and continuously generate the nicked fragments (NFs). Because the released NFs each have a palindromic sequence and daughter nicking site at the 3' end, they hybridize with each other, followed by alternately extension by polymerase and nicking by endonuclease. This leads to S-SDA effect, and the released single-stranded products in turn hybridize with NFs, accomplishing the rs-CCA process. When the Sybr Green I dyes intercalate into double-stranded DNA products, the lified fluorescence signal is achieved. Thus, the target miRNA can be detected down to 5 pM. Importantly, the rs-CCA system is capable of distinguishing the single base difference between target miRNAs, indicating the high sequence specificity. Moreover, its potential application in disease diagnosis was demonstrated via detecting target miRNA in complex biological matrix and analyzing the total RNAs extracted from HeLa cells. As a proof-of-concept building, the impressive rs-CCA scheme is expected to provide a valuable insight into constructing powerful signal lification strategies via sophisticated combination of biotechnologies available for nucleic acid manipulation and significantly benefit biomedical research and disease diagnostics.
Location: United States of America
Location: Portugal
No related grants have been discovered for Huo Xu.