ABSTRACT
Macrophages are the primary effectors against potential pathogen infections. They can be "parasitized" by intracellular bacteria, serving as "accomplices", protecting intracellular bacteria and even switching them to persisters. Here, using a freeze-thaw strategy-based microfluidic chip, a "Themis" nanocomplex (TNC) is created. The TNC consists of Lactobacillus reuteri-derived membrane vesicles, heme, and vancomycin, which cleaned infected macrophages and enhanced uninfected macrophages. In infected macrophages, TNC releases heme that led to the reconstruction of the respiratory chain complexes of intracellular persisters, forcing them to regrow. The revived bacteria produces virulence factors that destroyed host macrophages (accomplices), thereby being externalized and becoming vulnerable to immune responses. In uninfected macrophages, TNC upregulates the TCA cycle and oxidative phosphorylation (OXPHOS), contributing to immunoenhancement. The combined effect of TNC of cleaning the accomplice (infected macrophages) and reinforcing uninfected macrophages provides a promising strategy for intracellular bacterial therapy.
Subject(s)
Macrophages , Macrophages/metabolism , Animals , Mice , Freezing , Vancomycin/pharmacology , RAW 264.7 Cells , Heme/metabolism , Oxidative Phosphorylation/drug effects , Lab-On-A-Chip Devices , Citric Acid Cycle/drug effectsABSTRACT
Diabetic periodontitis is a major complication of diabetes, which has a deep involvement in teeth loss and more serious systematic diseases, including Alzheimer's disease, atherosclerosis and cancers. Diabetic periodontitis is difficult to treat because of recalcitrant infection and hyperglycemia-induced tissue dysfunction. Current treatments fail to completely eliminate infection due to the diffusion-reaction inhibition of biofilm, and ignore the tissue dysfunction. Here, we design a glucose-driven transformable complex, composed of calcium alginate (CaAlg) hydrogel shell and Zeolitic imidazolate framework-8 (ZIF-8) core encapsulating Glucose oxidase (GOx)/Catalase (CAT) and Minocycline (MINO), named as CaAlg@MINO/GOx/CAT/ZIF-8 (CMGCZ). The reaction product of glucose-scavenging, gluconic acid, could dissolve ZIF-8 core and transform CMGCZ from inflexible to flexible, facilitating the complex to overcome the diffusion-reaction inhibition of biofilm. Meanwhile, reduced glucose concentration could ameliorate the pyroptosis of macrophages to decrease the secretion of pro-inflammatory factors, thereby reducing inflamm-aging to alleviate periodontal dysfunction.
ABSTRACT
Solanum sisymbriifolium is a critical wild eggplant resource with resistance to many serious diseases that affect eggplant production. In this study, the chloroplast genome of S. sisymbriifolium was successfully sequenced using Illumina high-throughput sequencing technology. The length of the complete chloroplast genome is 155,771 bp, and its GC content is 37.76%. There is a large single-copy region (86,404 bp), a small single-copy region (18,525 bp), and a pair of inverted repeat regions (25,421 bp) in the chloroplast genome. A total of 128 coding genes were annotated in the entire chloroplast genome, including 83 protein-coding genes, 37 transfer RNA genes and eight ribosomal RNA genes. The phylogenetic tree of 17 complete chloroplast genomes shows that S. sisymbriifolium is closely related to Solanum wrightii.
