APPLIED AND ENVIRONMENTAL MICROBIOLOGY
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2020
·Vol. 86
·期 16
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IF 4.016
Han Li,Jiaxiu Wei,Jianxin Dong,Yudong Li,Yongquan Li,Yinghu Chen,Wenjun Guan
Streptomyces is well known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial Streptomyces strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigated the correlation between oil metabolism and salinomycin biosynthesis in Streptomyces albus ZD11, which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in S. albus ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl coenzyme A biosynthesis in S. albus ZD11. Multiple secreted lipases, which catalyze TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our results suggest that enhanced TAG hydrolysis and fatty acid degradation contribute to the high efficiency of oil utilization in S. albus ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis.IMPORTANCE In order to obtain high-level production of antibiotics, oils have been used as the main carbon source for some Streptomyces strains. Based on multiomics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in S. albus ZD11, an oil-preferring industrial Streptomyces strain. Our investigation into TAG hydrolysis yielded further evidence that this strain utilizes complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity for medium- and long-chain TAGs. Our findings represent a good start toward clarifying the complicated relationship between TAG catabolism and high-level antibiotic production in the industrial strains.
研究领域:
微生物学
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生物化学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Jianguo Wang,Jianyong Zhuo,Yaoye Tao,Shengjun Xu,Zun Chen,Fan Yang,Qinghong Ke,Haiyang Xie,Shusen Zheng,Hangxiang Wang,Xiao Xu
Background There is currently no effective treatment for advanced hepatocellular carcinoma (HCC), and chemotherapy has little effect on long-term survival of HCC patients, largely due to the cancer stem cell (CSC) chemoresistance of HCC.Methods We constructed a small-molecule nanometer-sized prodrug (nanoprodrug) loaded with salinomycin (SAL) for the treatment of HCC. SAL was encapsulated by the prodrug LA-SN38 (linoleic acid modified 7-ethyl-10-hydroxycamptothecin) to construct a self-assembled nanoprodrug further PEGylated with DSPE-PEG2000. We characterized this codelivered nanoprodrug and its antitumor activity both in vitro in human HCC cell lines and in vivo in mice.Results Delivery of the SAL- and LA-SN38-based nanoprodrugs effectively promoted apoptosis of HCC cells, exerted inhibition of HCC tumor-sphere formation as well as HCC cell motility and invasion, and reduced the proportion of CD133+ HCC-CSC cells. In nude mice, the nanoprodrug suppressed growth of tumor xenografts derived from human cell lines and patient.Conclusion Our results show that SAL-based nanoprodrugs are a promising platform for treating patients with HCC and a novel strategy for combination therapy of cancers.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
高影响因子
Food Analytical Methods
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2017
·Vol. 10
·期 9
·3042-3051
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IF 2.038
Tian Wenhao,Zhang Xiaoxiao,Song Meirong,Jiang Haiyang,Ding Shuangyang,Shen Jianzhong,Li Jiancheng
Polyether antibiotics have been widely used for the treatment and prevention of coccidiosis in chicken farming. In the present study, an efficient, simple and inexpensive competitive indirect enzyme-linked immunosorbent assay (ciELISA) method based on immunomagnetic sample clean up was developed for salinomycin. Monoclonal antibodies were immobilized on the surface of carboxylic acid magnetic beads (2.8 μm in diameter). After a simple extraction, residues in sample extracts were specifically adsorbed and the supernatant removed by magnetic separation. Analytes retained on the beads were then released by elution prior to ciELISA. The limit of detection for salinomycin in chicken muscle and liver was 22 and 18 ng mL −1 , respectively, and the linear quantitative range was 47–653 ng mL −1 . Intra-assay recoveries ranged from 86.00 to 99.32%, and inter-assay recoveries were between 85.68 and 96.34%. The inhibition efficiency and sensitivity of this method was improved compared with traditional hydrophilic-lipophilic balance column clean up ciELISA. Furthermore, the convenience and repeatability of the immunomagnetic cleanup renders the new method of high value for the analysis of drug residues in complex matrices.
The test method of schematic diagram
研究领域:
兽医学
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分析化学
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食品安全
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2018
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IF 3.997
De-Sheng Liang,Jian Liu,Tao-Xing Peng,Hui Peng,Feng Guo,Hai-Jun Zhong
Cancer stem cells (CSCs) can resist conventional chemotherapy to lead to cancer recurrence. For complete eradication of cancers, an effective CSCs therapeutic strategy should be developed to combine with conventional chemotherapy. In this work, a novel vitamin E-based redox-sensitive salinomycin (SAL, an inhibitor for CSCs) prodrug nanoparticles (TS NPs) and hyaluronic acid (HA)-coated TS NPs (HTS NPs) were fabricated to deliver paclitaxel (PTX) for cancer-targeted and combined chemotherapy. Both TS and HTS prodrug NPs had mean diameter of about 200 nm with uniform size distribution, excellent drug loading capacity for PTX, and glutathione-triggered SAL and PTX release profiles. The HTS prodrug NPs had enhanced cellular uptake efficiency over TS NPs due to CD44 receptor-mediated endocytosis, hence exerting stronger potency of SAL upon CSCs-enriched mammospheres formation and G 0 /G 1 cell phase arresting. Cytotoxicity and 3D tumor spheroids assays demonstrated that both TS and HTS prodrug NPs themself can synergize with loaded PTX to maximize the chemotherapeutic effect. Obviously, the latter demonstrated a more potent anticancer efficacy due to improved intracellular drug delivery efficiency. These results suggested that the designed TS prodrug NPs, especially the coated HTS NPs can serve as an effective anti-CSCs strategy for cancer targeted and combination treatments.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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癌症研究
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PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Yong-jun Chen,Zi-tao Guo,Hai-qiao Chen,Shi-fan Zhang,Ying-xia Bao,Zhoufan Xie,Jia-le Ke,Wen-jie Ye,Jia-cheng Liang,Jia-chen Chen,Ning Li,Feng-xin Zheng,Hui Liao,Ting Wu,Jian-xin Pang
Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed. In this study, we first discovered that salinomycin, an antibiotic, can regulate uric acid homeostasis and ameliorate kidney damage in mice with HN. Mechanistically, salinomycin inhibited serum and hepatic xanthine oxidase (XOD) activities and downregulated renal urate transporter 1 (URAT1) expression and transport activity, thus exerting uric acid-lowering effects in mice with HN. Furthermore, we found that salinomycin promoted p-NRF2 Ser40 expression, resulting in increased nuclear translocation of NRF2 and activation of NRF2. More importantly, salinomycin affected the gut microbiota and promoted the generation of short-chain fatty acids (SCFAs) in mice with HN. In conclusion, our results revealed that salinomycin maintains uric acid homeostasis and alleviates kidney injury in mice with HN by multiple mechanisms, suggesting that salinomycin might be a desirable candidate for HN treatment in the clinic.
研究领域:
药理学
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肾病学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
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