Emerging Microbes & Infections
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2024
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IF 8.4
Jinxin Zheng,Xiaoju Liu,Yanpeng Xiong,Qingyin Meng,Peiyu Li,Fan Zhang,Xiaoming Liu,Zhiwei Lin,Qiwen Deng,Zewen Wen,Zhijian Yu
The rapid proliferation of multidrug-resistant (MDR) bacterial pathogens poses a serious threat to healthcare worldwide. Carbapenem-resistant (CR) Enterobacteriaceae, which have near-universal resistance to available antimicrobials, represent a particularly concerning issue. Herein, we report the identification of AMXT-1501, a polyamine transport system inhibitor with antibacterial activity against Gram-positive and -negative MDR bacteria. We observed minimum inhibitory concentration (MIC)50/MIC90 values for AMXT-1501 in the range of 3.13–12.5 μM (2.24–8.93 μg /mL), including for methicillin-resistant Staphylococcus aureus (MRSA), CR Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. AMXT-1501 was more effective against MRSA and CR E. coli than vancomycin and tigecycline, respectively. Subinhibitory concentrations of AMXT-1501 reduced the biofilm formation of S. aureus and Enterococcus faecalis. Mechanistically, AMXT-1501 exposure damaged microbial membranes and increased membrane permeability and membrane potential by binding to cardiolipin (CL) and phosphatidylglycerol (PG). Importantly, AMXT-1501 pressure did not induce resistance readily in the tested pathogens.
研究领域:
微生物学
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药理学
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感染病学
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DOI
PubMed
高影响因子
Interdisciplinary Medicine
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2025
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IF 13.6
Liping Yang,Fangli Liao,Yanran Tong,Tong Huang,Yan-e Du,Siyang Wen,Linshan Jiang,Lanlang Peng,Hua Sun,Gaoli Zhang,Weixian Chen
Cancer stem cells exhibit flexible metabolic profiles. However, the underlying mechanisms for differential metabolic pathways affecting stemness maintenance in gastric cancer are poorly understood. Here, we reveal the role of serine hydroxymethyltransferase-2 (SHMT2)/serine-mediated crosstalk between one-carbon metabolism and lipid metabolism in the stemness maintenance of gastric cancer. Clinically, SHMT2 was significantly highly expressed in Gastric cancer cells (GCs) and gastric cancer stem cells, and was associated with clinical malignant features and poor prognosis in gastric cancer patients. Mechanistically, inhibition of SHMT2 expression resulted in diminished serine levels in one-carbon metabolism, which subsequently modified the composition and fluidity of membrane phospholipids, leading to a reduction in lipid rafts within cellular membranes. The remodeling of membrane phospholipids hindered the localization of γ-secretase to lipid rafts, thereby inhibiting the cleavage of CD44 and the subsequent production of CD44-ICD. Consequently, the transcriptional regulation of c-Myc and KLF4 by CD44-ICD was reduced, ultimately disrupting the maintenance of stemness in gastric cancer cells. Together, these results provide compelling evidence for the metabolic adaptability of cancer stem cells, and the SHMT2/serine/lipid rafts signaling axis holds promise as a potential biomarker for the diagnosis and prognosis of gastric cancer. Furthermore, we synthesized HA-Exo-si SHMT2 to investigate targeted therapy for GC, offering a novel approach for the clinical treatment of gastric cancer.
研究领域:
生物化学
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分子生物学
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肿瘤学
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DOI
高影响因子
JOURNAL OF DAIRY SCIENCE
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2016
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IF 2.408
Hong-Hao Jin,Qun Lu,Jian-Guo Jiang
Using thin film ultrasonic dispersion method, the curcumin liposomes were prepared with milk fat globule membrane (MFGM) phospholipids and soybean lecithins, respectively, to compare the characteristics and stability of the 2 curcumin liposomes. The processing parameters of curcumin liposomes were investigated to evaluate their effects on the encapsulation efficiency. Curcumin liposomes were characterized in terms of size distribution, ζ-potential, and in vitro release behavior, and then their storage stability under various conditions was evaluated. The curcumin liposomes prepared with MFGM phospholipids had an encapsulation efficiency of about 74%, an average particle size of 212.3 nm, and a ζ-potential of −48.60 mV. The MFGM liposomes showed higher encapsulation efficiency, smaller particle size, higher absolute value of ζ-potential, and slower in vitro release than soybean liposomes. The retention rate of liposomal curcumin was significantly higher than that of free curcumin. The stability of the 2 liposomes under different pH was almost the same, but MFGM liposomes displayed a slightly higher stability than soybean liposomes under the conditions of Fe 3+ , light, temperature, oxygen, and relative humidity. In conclusion, MFGM phospholipids have potential advantages in the manufacture of curcumin liposomes used in food systems.
研究领域:
食品科学
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药剂学
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材料科学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2025
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IF 9.8
Weijia Zhang,Jingqi Shen,Tianhong Liu,Chenghua Chen,Jinlin Wang,Fan Bai,Peng Xu,Ruichang Gao,Yuanhui Zhao,Xinxing Xu
This novel study explored how “roe rubbing” and “salt mixing” qualitatively transform fish roe into caviar, focusing on membrane phospholipids (PLs) and proteins. Salt mixing increased phosphatidylcholine (PC) concentration in membrane PLs, while DHA, linolenic acid, and linoleic acid levels decreased. After roe rubbing and salt mixing, Raman spectra of membrane PLs decreased at 1300, 1450, and 1655 cm −1 , indicating decreased torsional freedom of motion and C C telescopic vibration intensity. The hydrophobic environment formed by salt and interchain repulsion led to hydrogen bonding network, causing conformational changes in membrane proteins and increases in α-helix, β-sheet composition. Roe rubbing induced temporary disruption of protein chemical bonds, while eliminating contaminants mitigated off-flavors and improved the tissue condition. Salt caused osmotic pressure to release more lipids, which increased membrane thickness and consistent internal pore size, giving caviar elasticity and fullness. This work enhanced theoretical direction for caviar processing quality.
研究领域:
食品科学
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生物化学
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食品加工
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光谱学
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膜生物物理学
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产品关联
DOI
PubMed
高影响因子
ACS Infectious Diseases
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2025
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IF 3.8
Xiaoju Liu,Congcong Li,Qingyin Meng,Chengchun Chen,Yingying Lai,Hongyan Wang,Zhijian Yu,Duoyun Li,Zhong Chen,Tieying Hou
Derazantinib (DZB), a pan-fibroblast growth factor receptor (FGFR) inhibitor, exhibits potent activity against FGFR1–3 kinases and has been clinically approved for antitumor therapy. However, its antibacterial properties remain unknown. Here, we demonstrated that DZB displays broad-spectrum activity against Staphylococcus aureus (S. aureus), with minimum inhibitory concentrations (MICs) ranging from 6.25 to 25 μM. DZB exhibited more rapid and stronger bactericidal activity against planktonic cells of both MSSA and MRSA compared to vancomycin. DZB at 6.25 μM robustly inhibited biofilm formation and even eradicated mature biofilms. Global proteomic profiling revealed that DZB’s antibacterial mechanism might involve disruption of microbial glycolysis/gluconeogenesis pathways. Furthermore, in vitro selection of DZB-induced resistant S. aureus resulted in a 2-fold increase in MIC, and whole-genome sequencing of this derivative isolate identified amino acid mutations in membrane-associated proteins. DZB was found to compromise bacterial membrane integrity, as evidenced by increased membrane permeability, and the membrane damage was also confirmed by scanning electron microscopy (SEM). The antibacterial activity of DZB was neutralized by the addition of exogenous phosphatidylglycerol and cardiolipin. Biolayer interferometry assays demonstrated a strong interaction between DZB and cardiolipin, suggesting membrane phospholipid targeting as a key mechanism. Lastly, DZB displayed a robust inhibitory effect against intracellular S. aureus SA113 and showed excellent in vivo anti-MRSA infection in both Galleria mellonella larvae and murine infection models. In summary, our findings established DZB as a promising anti-S. aureus agent with dual antibacterial and antibiofilm activities by disrupting the cell membrane through targeting membrane phospholipids.
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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