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ANALYST · 2024 · IF 3.6

Qualitative and quantitative rapid detection of VOCs differentially released by VAP-associated bacteria using PTR-MS and FGC-PTR-MS

Wei Xu,Xue Zou,Yueting Ding,Qi Zhang,Yulan Song,Jin Zhang,Min Yang,Zhou Liu,Qiang Zhou,Dianlong Ge,Qiangling Zhang,Wencheng Song,Chaoqun Huang,Chengyin Shen,Yannan Chu

Ventilator-associated pneumonia (VAP) is a prevalent disease caused by microbial infection, resulting in significant morbidity and mortality within the intensive care unit (ICU). The rapid and accurate identification of pathogenic bacteria causing VAP can assist clinicians in formulating timely treatment plans. In this study, we attempted to differentiate bacterial species in VAP by utilizing the volatile organic compounds (VOCs) released by pathogens. We cultured 6 common bacteria in VAP in vitro, including Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Staphylococcus aureus, which covered most cases of VAP infection in clinic. After the VOCs released by bacteria were collected in sampling bags, they were quantitatively detected by a proton transfer reaction-mass spectrometry (PTR-MS), and the characteristic ions were qualitatively analyzed through a fast gas chromatography-proton transfer reaction-mass spectrometry (FGC-PTR-MS). After conducting principal component analysis (PCA) and analysis of similarities (ANOSIM), we discovered that the VOCs released by 6 bacteria exhibited differentiation following 3 h of quantitative cultivation in vitro. Additionally, we further investigated the variations in the types and concentrations of bacterial VOCs. The results showed that by utilizing the differences in types of VOCs, 6 bacteria could be classified into 5 sets, except for A. baumannii and E. cloacae which were indistinguishable. Furthermore, we observed significant variations in the concentration ratio of acetaldehyde and methyl mercaptan released by A. baumannii and E. cloacae. In conclusion, the VOCs released by bacteria could effectively differentiate the 6 pathogens commonly associated with VAP, which was expected to assist doctors in formulating treatment plans in time and improve the survival rate of patients.

研究领域: 医学 · 微生物学 · 分析化学
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MATERIALS & DESIGN · 2026 · IF 8.2

VAP peptide-modified Forsythiaside A-pretreated exosomes promote the repair of the blood-spinal cord barrier by regulating endothelial cell autophagy

Xiaotian Zhang,Qian Zhu,Ziqing Zhu,Peiran Chan,Zhiyuan Chen,Yongxin Huang,Fuqiang Chen,Zhe Yu,Juan Wang,Yantian Su

FSA-pretreated Huc-MSCs generate potent exosomes to promote BSCB repair via TJs. • VAP peptide targets FSA-Exos to SCI endothelium via GRP78 for precise repair. • VAP-Exos promote BSCB repair by regulating endothelial cell autophagy. Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), triggering secondary damage and permanent neurological deficits. Forsythiaside A is a natural bioactive compound isolated from Forsythia suspensa. It boasts robust anti-inflammatory and tissue-repairing capacities and can precondition stem cells to enhance the therapeutic potency of their secreted exosomes. To equip FSA-primed exosomes with precise targeting, we utilized SNTRVAP (VAP), a GRP78-specific peptide with the sequence SNTRVAP. Here, we constructed VAP-Exos by conjugating VAP onto FSA-preconditioned human umbilical cord mesenchymal stem cell exosomes, which effectively restore BSCB integrity. Binding GRP78 to target endothelial cells, VAP-Exos upregulates tight junction proteins (ZO-1, Occludin, Claudin5) and lowers BSCB permeability. Single-nucleus sequencing proves they stimulate endothelial proliferation, elevate Itga5, and activate autophagy pathways; elevated autophagic flux is validated by increased LC3-II/I ratio and P62 degradation. Meanwhile, VAP-Exos alleviate oxidative stress, shift microglia toward the anti-inflammatory M2 phenotype, and rebalance the spinal immune microenvironment. In vivo assays on SCI mice show smaller lesions, attenuated glial scarring and recovered motor function. Collectively, VAP-Exos safeguard BSCB integrity through endothelial autophagy modulation, representing a promising engineered exosome candidate for SCI therapy. Download: Download high-res image (184KB) Download: Download full-size image

CAS / MDL: 314-13-6
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Asian Journal of Pharmaceutical Sciences · 2024 · IF 10.7

All-stage targeted nanodiscs for glioma treatment by inducing cuproptosis and apoptosis of cancer cells and cancer stem cells

Yuan Ding,Ruohan Chen,Jianfen Zhou,Yanning Bao,Nana Meng,Xudong Zheng,Shengmin Yang,Jiasheng Lu,Zhixuan Jiang,Yu Liu,Cao Xie,Linwei Lu,Weiyue Lu

There remain several intractable challenges for chemotherapy in glioma treatment, including the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and tumor heterogeneity caused by cancer stem cells (CSCs), which are resistant to conventional chemotherapy. Here, we established a nano strategy to kill glioma cells and CSCs, combining carfilzomib and bis(diethyldithiocarbamate)copper. The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis. The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site. This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.

CAS / MDL: 20624-25-3
研究领域: 肿瘤学 · 药理学 · 纳米技术 · 神经科学
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