Microbiology Spectrum
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2025
·
IF 3.8
Yuhan Yang,Panjie Hu,Yanchun Gong,Zeyong Zhong,Yichi Zhang,Fan Ye,Tieli Zhou,Jianming Cao,Zhongyong Wang
Multidrug-resistant gram-negative bacteria (GNB) have posed a serious public health hazard worldwide. Colistin (COL), the ultimate therapeutic option for treating GNB infections, has had escalating resistance rates concomitant with increased utilization. In this study, we attempted to increase the sensitivity to COL using a plant extract, α-terpineol (α-TP). Checkerboard and time-kill assays indicated that the combination of COL and α-TP exhibited pronounced synergistic antimicrobial effects against colistin-resistant (COL-R) GNB in vitro. Biofilm assessments revealed that COL combined with α-TP effectively inhibited biofilm development and eliminated established biofilms. Scanning electron microscopy indicated substantial disruption of bacterial cell membranes after 6 h of combined treatment. Additionally, cytotoxicity and erythrocyte hemolysis assays confirmed that α-TP maintained a degree of safety at synergistic concentrations. Mechanistically, the combination of COL and α-TP promoted the accumulation of reactive oxygen species and enhanced the permeability of both the inner and outer bacterial membranes. This study demonstrated that α-TP can restore the sensitivity of COL-R GNB to COL when used in combination.
研究领域:
微生物学
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感染病学
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抗菌药物研究
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药理学
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分子生物学
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转化医学
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耐药机制研究
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 7
·1518
·
IF 6.525
Mengchen An,Mengxiao Shi,Jingjing Su,Yueru Wei,Rongrong Luo,Pengchao Sun,Yongxing Zhao
Although the inhibitors of the interleukin-6 receptor (IL-6R) and tumor necrosis factor-α (TNF-α) have achieved a certain success in the clinical treatment of rheumatoid arthritis (RA), great effort should be made to overcome side effects and to improve patient compliance. The present research aimed to address these problems by the co-delivery of tocilizumab (TCZ)—an inhibitor of IL-6R—and an aptamer Apt1-67, which specifically inhibits TNF receptor 1 via separable microneedles (MN). MN were featured with a sustained release of TCZ from needle tips and a rapid release of Apt1-67 from needle bodies by using methacrylate groups grafted hyaluronic acid as the fillings of needle tips and polyvinyl alcohol/polyvinyl pyrrolidone as the fillings of needle bodies. Our results demonstrated that TCZ and Apt1-67 were distributed in MN as expected, and they could be released to the surroundings in the skin. In vivo studies revealed that combined medication via MN (TCZ/[email protected]) was superior to MN loaded with a single drug. Compared with subcutaneous injection, TCZ/[email protected]was of great advantage in inhibiting bone erosion and alleviating symptoms of CIA mice. This study not only provides a novel approach for combined medication with different release properties but also supplies a strategy for improving drug efficacy.Keywords:separable microneedles;tocilizumab;aptamer Apt1-67;rheumatoid arthritis
研究领域:
药学
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生物医学工程
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Life-Basel
·
2025
·Vol. 15
·期 12
·1920
·
IF 3.4
Chenliang Chu,Liang Qin,Huayong Peng,Tao Kuang,Yongshi Li,Xin Wang,Fenglan Liang,Ping Gao,Xiaoxiong Wang,Deyun Ma
Methicillin-resistantStaphylococcus aureus(MRSA) poses a significant clinical challenge due to its multidrug resistance, particularly to β-lactam antibiotics. This study comprehensively evaluated the natural compound emodin for its anti-MRSAactivity, mechanisms of action, and potential for synergy with β-lactam antibiotics. Our findings demonstrate that emodin dose-dependently inhibitsMRSAgrowth and abrogates biofilm formation at 2× MIC. Mechanistic studies revealed that emodin compromises cell membrane and wall integrity, induces oxidative stress, and downregulates the virulence factors SPA and EsxA. Furthermore, emodin acted synergistically with β-lactam antibiotics: it enhanced the ability of cefalexin to block bacterial adhesion and invasion of HaCat cells, and potentiated the efficacy of amoxicillin in clearingMRSAfrom infected macrophages. In conclusion, emodin employs a multi-target mechanism againstMRSAand can resensitize the bacterium to conventional β-lactam antibiotics, presenting a promising strategy for combination therapy that may help curb antibiotic use and resistance development.
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产品关联
DOI
PubMed
高影响因子
Small Methods
·
2024
·
IF 10.7
Chao Wan,Longyu Yi,Huijuan Yuan,Shunji Li,Xin Wang,Yuxiao Shu,Han Xie,Mengcheng Lei,Zeyu Miao,Wei Du,Xiaojun Feng,Yiwei Li,Peng Chen,Bi-Feng Liu
In microbiological research, traditional methods for bacterial screening and antibiotic susceptibility testing are resource-intensive. Microfluidics offers an efficient alternative with rapid results and minimal sample consumption, but the demand for cost-effective, user-friendly platforms persists in communities and hospitals. Inspired by the Magdeburg hemispheres, the strategy adapts to local conditions, leveraging omnipresent atmospheric pressure for self-sealing of Rotation-SlipChip (RSC) equipped with a 3D circular Christmas tree-like microfluidic concentration gradient generator. This innovative approach provides an accessible and adaptable platform for microbiological research and testing in diverse settings. The RSC can avoid leakage concerns during multiple concentration gradient generation, chip-rotating, and final long-term incubation reaction (≥24 h). Furtherly, RSC subtypes adapted to different reactions can be fabricated in less than 15 min with cost less than $1, the result can be read through designated observational windows by naked-eye. Moreover, the RSC demonstrates its capability for evaluating bacterial biomarker activity, enabling the rapid assessment of β-galactosidase concentration and enzyme activity within 30 min, and the limit of detection can be reduced by 10-fold. It also rapidly determines the minimum antibiotic inhibitory concentration and antibiotic combined medications results within 4 h. Overall, these low-cost and user-friendly RSC make them invaluable tools in determinations at previously impractical environment.
研究领域:
微生物学
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生物技术
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医学诊断
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药学科学
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DOI
PubMed
高影响因子
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