1.Profiles of antibiotic resistance genes in the Lhasa River
Yayao LYU ; Qiumeng CHEN ; Haibei LI ; Shujuan LI ; Shujie LIU ; Yi ZHANG
Journal of Public Health and Preventive Medicine 2024;35(4):1-5
Objective To investigate the pollution of antibiotic resistance genes (ARGs) in the Lhasa River and provide a scientific basis for the safety of drinking water for the regional population and the prevention and control of water environment pollution. Methods A total of five water samples were collected in the Lhasa River in July 2022. Using quantitative real-time polymerase chain reaction (qPCR) assay, 19 types of ARGs, including eight “last-resort” ARGs (LARGs) were detected and analyzed. Statistical analysis was conducted using the SPSS 22.0 software, and Student's t-test was used to compare data between two groups. Results All the 19 ARGs were detected with high frequencies, with the aminoglycoside resistance gene aadA having the highest concentration, followed by the sulfonamide resistance gene sul1 and the macrolide resistance gene ermB. Among the eight LARGs, the carbapenem resistance gene blaOXA-48 had the highest concentration. The absolute and relative concentrations of LARGs were lower than those of common ARGs. There was a statistically significant difference in the absolute concentrations between them, but no significant difference was observed in the relative concentrations. Conclusion Both “conventional” ARGs and LAGRs have been detected in the Lhasa River. Although they are at a relatively low level compared to other domestic waters, in view of the serious adverse effects that ARGs, especially LARGs, may cause, the pollution of ARGs in the Lhasa River should be taken seriously.
2.Intelligent nanotherapeutic strategies for the delivery of CRISPR system.
Chao CHEN ; Wu ZHONG ; Shiyu DU ; Yayao LI ; Yunfei ZENG ; Kunguo LIU ; Jingjing YANG ; Xiaoxiang GUAN ; Xin HAN
Acta Pharmaceutica Sinica B 2023;13(6):2510-2543
CRISPR, as an emerging gene editing technology, has been widely used in multiple fields due to its convenient operation, less cost, high efficiency and precision. This robust and effective device has revolutionized the development of biomedical research at an unexpected speed in recent years. The development of intelligent and precise CRISPR delivery strategies in a controllable and safe manner is the prerequisite for translational clinical medicine in gene therapy field. In this review, the therapeutic application of CRISPR delivery and the translational potential of gene editing was firstly discussed. Critical obstacles for the delivery of CRISPR system in vivo and shortcomings of CRISPR system itself were also analyzed. Given that intelligent nanoparticles have demonstrated great potential on the delivery of CRISPR system, here we mainly focused on stimuli-responsive nanocarriers. We also summarized various strategies for CIRSPR-Cas9 system delivered by intelligent nanocarriers which would respond to different endogenous and exogenous signal stimulus. Moreover, new genome editors mediated by nanotherapeutic vectors for gene therapy were also discussed. Finally, we discussed future prospects of genome editing for existing nanocarriers in clinical settings.
3.Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2022;12(11):4224-4234
Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.
4.Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2024;14(2):897-899
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].