SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Qingbin Yuan,Yi Wang,Shangjie Wang,Ruiqing Li,Junlu Ma,Yijing Wang,Ruonan Sun,Yi Luo
Despite severe threats of extracellular antibiotic resistance genes (eARGs) towards public health in various environments, advanced studies have been hindered mainly by ineffective extracellular DNA (exDNA) extraction methods, which is challenged by trace levels of exDNA and inference from abundant coexisting compounds. This study developed a highly selective exDNA extraction method based on molecular imprinting technology (MIT) by using adenine as the template for the first time. Results suggested that adenine imprinted beads were rough spheres at an average size of 0.39 ± 0.07 μm. They effectively adsorbed DNA in the absence of chaotropic agents, with superior capacity (796.2 mg/g), rate (0.0066/s) and regarding DNA of variable lengths, even the ultra-short DNA (<100 bp). They were also highly selective towards DNA, circumventing the interference of competitive compounds' interference. These properties contribute to efficient exDNA extraction (71 %–119 %) from various environmental samples. Specifically, adenine imprinted beads enabled significantly higher extraction rates of eARGs from river, air and vegetable samples (69 %–95 %) compared to that by commercial DNA extraction products (16 %–62 %). The adenine imprinted beads-based method reveals underestimated eARG levels in the environment and the corresponding risks, and thus will thus be a powerful tool for advanced exDNA research.
研究领域:
微生物学
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环境科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2022
·
IF 6.064
Wang Meng,Deng Zifeng,Li Yanmei,Xu Keyong,Ma Yi,Yang Shang-Tian,Wang Jufang
Pseudomonas aeruginosa (P. aeruginosa), an opportunistic pathogen, is often associated with difficulties in treating hospital-acquired infections. Biofilms formed by P. aeruginosa significantly improve its resistance to antimicrobial agents, thereby, posing a great challenge to the combat of P. aeruginosa infection. Antimicrobial peptides (AMPs) have recently emerged as promising antibiofilm agents and increasingly attracting the attention of scientists worldwide. However, current knowledge of their antibiofilm behavior is limited and their underlying mechanism remains unclear. In this study, a novel AMP, named PEW300, with three-point mutations (E9H, D17K, and T33A) from Cecropin A was used to investigate its antibiofilm property and antibiofilm pathway against P. aeruginosa. PEW300 displayed strong antibacterial and antibiofilm activity against P. aeruginosa with no significant hemolysis or cytotoxicity to mouse erythrocyte and human embryonic kidney 293 cells. Besides, the antibiofilm pathway results showed that PEW300 preferentially dispersed the mature biofilm, leading to the biofilm-encapsulated bacteria exposure and death. Meanwhile, we also found that the extracellular DNA was a critical target of PEW300 against the mature biofilm of P. aeruginosa. In addition, multiple actions of PEW300 including destroying the cell membrane integrity, inducing high levels of intracellular reactive oxygen species, and interacting with genomic DNA were adopted to exert its antibacterial activity. Moreover, PEW300 could dramatically reduce the virulence of P. aeruginosa. Taken together, PEW300 might be served as a promising antibiofilm candidate to combat P. aeruginosa biofilms.
研究领域:
微生物学
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分子生物学
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传染病学
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药学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Hongyu Shi,Xinyi Hu,Jin Zhang,Wenxuan Li,Jiang Xu,Baolan Hu,Liping Ma,Liping Lou
Soil environment is a vital place for the occurrence and spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Extracellular DNA-mediated transformation is an important pathway for ARGs horizontal transfer and widely exists in soil environment. However, little information is available on how common soil components affect ARGs transformation. Here, three minerals (quartz, kaolinite , and montmorillonite) and three organic matters (humic acid, biochar, and soot) were selected as typical soil components. A small amount in suspension (0.2 g/L) of most soil components (except for quartz and montmorillonite) promoted transformant production by 1.1–1.6 folds. For a high amount (8 g/L), biochar significantly promoted transformant production to 1.5 times, kaolinite exerted a 30 % inhibitory effect. From the perspective of plasmid, biochar induced a higher proportion of supercoiled plasmid than kaolinite; more dissolved organic matter and metal ions facilitated plasmid aggregation under the near-neutral pH, thus promoted transformation. As for the influence of materials on recipient, although biochar and kaolinite both increased reactive oxygen species (ROS) level and membrane permeability, biochar up-regulated more ROS related genes, resulting in intracellular ROS production and up-regulating the expression of carbohydrate metabolism and transformation related genes. While kaolinite inhibited transformation mainly by causing nutrient deficiency.
研究领域:
环境科学
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微生物学
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土壤学
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遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2023
·
IF 6.2
Cong Wei,Peipei Li,Lixin Liu,Hong Zhang,Tianyu Zhao,Yongming Chen
Following brain trauma, secondary injury from molecular and cellular changes causes progressive cerebral tissue damage. Acute/chronic neuroinflammation following traumatic brain injury (TBI) is a key player in the development of secondary injury. Rapidly elevated cell-free DNAs (cfDNAs) due to cell death could lead to production of inflammatory cytokines that aggravate TBI. Herein, we designed poly(amino acid)-based cationic nanoparticles (cNPs) and applied them intravenously in a TBI mice model with the purpose of scavenging cfDNA in the brain and suppressing the acute inflammation. In turn, these cNPs could effectively eliminate endogenous cfDNA, inhibit excessive activation of inflammation, and promote neural functional recovery.
研究领域:
神经科学
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药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xingliang Liu,Shi Chen,Lixin Liu,Yongming Chen
Abnormally high level of cell-free DNA (cfDNA) is one of the important causes of autoimmune diseases, which aggravate the symptoms of rheumatoid arthritis (RA). Recently, the utilization of cationic polymeric nanoparticles for scavenging cfDNA has emerged as a promising therapeutic strategy for the treatment of RA. However, the intravenous introduction of cationic polymeric nanoparticles into the circulation carries a risk of dissociation, causing toxicity. To realize the potential clinical translation, we employed a series of silica particles grafted with poly(2-(dimethylamino) ethyl methacrylate) (PDMA) (SiNP@PDMA) brush, which possess adjustable PDMA content (100, 200, and 300 degree of polymerization (DP)) and particle size (50, 100, and 200 nm diameter), to selectively scavenge cfDNA in inflamed joint cavity. We demonstrate that the binding affinity for cfDNA, cytotoxicity, circulation time in vivo and retention in the inflamed joint cavity are influenced by the core-shell structure of SiNP@PDMA, ultimately impacting therapeutic efficacy. Among them, SiNP@PDMA with 100 nm size and 200 DP of PDMA exhibit enhanced accumulation and prolonged retention time in inflammatory joint cavity, resulting in superior therapeutic effect. Therefore, in this study, applying the precisely tuning size and cation content of SiNP@PDMA, we demonstrated the factors to matter the therapeutic effect of cationic nanoparticles, which deepened the understanding of the anti-inflammatory therapies based on cfDNA scavenger for RA. Statement of significance Inspired by the discovery that cfDNA would induce inappropriate immune responses to exacerbate the progress of RA, we innovatively employed SiNP@PDMA as a cfDNA scavenger to inhibit cfDNA-induced inflammation in RA. Increase in the cation content efficiently strengthened the binding between SiNP@PDMA and cfDNA, leading to an improvement in inhibitory effect of inflammation. In addition, we compared the behaviors of 50, 100 and 200 nm SiNP@PDMA in RA symptom suppression, local cfDNA scavenging and inflammation inhibition. The results demonstrated that SiNP 100 -PDMA 200 outperformed other analogues, corresponding to their more favorable distribution in inflammatory articular cavity. Together, this study revealed the structure-property relationship of cfDNA scavengers for further development of safe and effective cfDNA scavenging system.
研究领域:
纳米技术
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风湿病学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yanzi Yan,Huiyi Liang,Xingliang Liu,Lixin Liu,Yongming Chen
Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.
研究领域:
药学
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纳米技术
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皮肤科
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 27
·2000391
·
IF 16.836
Jingjiao Wu,Huiyi Liang,Yuanchao Li,Yi Shi,Massimo Bottini,Yongming Chen,Lixin Liu
A high concentration of cell-free DNA (cfDNA) in joints is considered a disease causative agent of rheumatoid arthritis (RA) and cfDNA scavenging has been regarded as an efficient therapeutic avenue. Cationic polymers can hamper progression of joint inflammation in a rat model of RA by scavenging cfDNA; however, they may cause systemic toxicity due to the strong positive charges. To reduce the toxicity, herein a library of cationic nanoparticles (cNPs) of block copolymer micelles is developed and the effects of structure and surface composition on cNP efficacy to bind nucleic acids, toxicity, and therapeutic activity on a collagen induced arthritis (CIA) rat model of RA are assessed. The library includes cNPs with a homoshell from poly(lactic- co -glycolic acid)- block -poly(2-(dimethylamino)ethyl methacrylate) (PLGA- b -PDMA) block copolymers and cNPs with a mixed shell of poly(ethylene glycol) (PEG) and PDMA by coself-assembling PLGA- b -PDMA and PLGA- b -PEG block copolymers. Relatively to the homoshell cNPs, introduction of PEG segments translates into a lower DNA binding efficacy while preserving ability to hamper joint inflammation. Moreover, they show a greater accumulation and longer retention at the inflamed joints, allowing a lower administration frequency. In conclusion, this work shows that the therapeutic index of cationic materials can be tuned by introducing surface neutral moieties.
研究领域:
纳米技术
·
生物材料
·
药学
·
风湿病学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Nature Communications
·
2018
·Vol. 9
·期 1
·1-14
·
IF 12.353
Liang Huiyi,Peng Bo,Dong Cong,Liu Lixin,Mao Jiaji,Wei Song,Wang Xinlu,Xu Hanshi,Shen Jun,Mao Hai-Quan,Gao Xiaohu,Leong Kam W.,Chen Yongming
Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
研究领域:
纳米医学
·
炎症性疾病
·
风湿病学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）