Antimicrobial peptides (AMPs) are usually small molecule peptides, which display broad-spectrum antimicrobial activity, high efficiency, and stability. For the multiple-antibiotic-resistant strains, AMPs play a significant role in the development of novel antibiotics because of their broad-spectrum antimicrobial activities and specific antimicrobial mechanism. Besides broad-spectrum antibacterial activity, AMPs also have anti-inflammatory activity. The neutralization of lipopolysaccharides (LPS) plays a key role in anti-inflammatory action of AMPs. On the one hand, AMPs can readily penetrate the cell wall barrier by neutralizing LPS to remove Gram-negative bacteria that can lead to infection. On the contrary, AMPs can also inhibit the production of biological inflammatory cytokines to reduce the inflammatory response through neutralizing circulating LPS. In addition, AMPs also modulate the host immune system by chemotaxis of leukocytes, to promote immune cell proliferation, epithelialization, and angiogenesis and thus play a protective role. This review summarizes some recent researches about anti-inflammatory AMPs, with a focus on the interaction of AMPs and LPS on the past decade.
The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. Here, we show that targeting both the vascular niche and perivascular fibroblasts establishes “hospitable soil” to foster incorporation of “seed”, in this case the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NADPH Oxidase 4 (NOX4) synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs (HgfiΔEC/iΔEC) aberrantly upregulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially-inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in HgfiΔEC/iΔEC mice recapitulated the phenotype of human and mouse fibrotic livers and lungs. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration.
Antibiotics are widely used in aquaculture. Intensive farming drives indiscriminate use of antibiotics, which results in residues of antibiotics in cultured aquatic products and bacterial resistance. This perspective attempts to present a brief update on usage, regulations, residues, and potential human health risk of antibiotics used in aquaculture. Through the comprehensive literature review, we provide a view that the safety of aquatic products still requires further attention and more rigorous risk assessment. Finally, we make a few suggestions for future research directions: reduce the use of antibiotics to bring down the speed of resistance development and monitor resistant pathogens and genes, strictly manage the environmental sanitation of aquaculture and pay attention to the quality of water bodies introduced into aquaculture, seek international cooperation to establish an information bank of antibiotic residues and antibiotic-resistant genes, and set up a quantitative model to assess the risk of antibiotic resistance associated with the antibiotic residues.
In this article, the uniaxial alignment of poly(3-hexylthiophene) (P3HT) nanofibrils with a π-π stacking growth direction in which P3HT chains adopt a flat-on conformation was obtained by solvent directional evaporation using a glass cover slide and a poly(dimethylsiloxane) (PDMS) sheet to press the P3HT film in a carbon disulfide (CS(2)) atmosphere. By controlling the CS(2) vapor pressure during the film-forming process, we got a well-oriented P3HT film whose order parameter reached as high as 0.97. The orientation of the film was induced by the crystallization nucleation of P3HT and the directional evaporation of the solvent. Under a CS(2) vapor atmosphere, P3HT crystals preferred to adopt the form II modification, which started by nucleation. Owing to the solvent directional evaporation from the center to the margin, P3HT at the center of the sample would precipitate first to induce nucleation. Then the peripheral P3HT would directly diffuse, precipitate, and then adhere to the nucleus to form the uniaxial alignment of P3HT nanofibrils along the direction of solvent evaporation. Furthermore, in the P3HT nanofibrils, the π-π stacking direction of P3HT lamellae was parallel to the crystal growth direction, which would provide an effective path for charge transport.
Antimicrobial peptides (AMPs) have been an attractive alternative to traditional antibiotics. However, considerable efforts are needed to further enhance their antimicrobial effects and stability against bacterial degradation. Tetrahedral framework nucleic acids (tFNAs), a new class of three-dimensional nanostructures, have been utilized as a delivery vehicle. In this study, tFNAs were combined for the first time with an antimicrobial peptide GL13K, and the effects of the resultant complexes against Escherichia coli (sensitive to GL13K) and Porphyromonas gingivalis (capable of degrading GL13K) were investigated. tFNA-based delivery enhanced the effects of GL13K against E. coli. The tFNA vehicle both increased bacterial uptake and promoted membrane destabilization. Moreover, it enhanced the effects of GL13K against P. gingivalis by protecting the peptide against degradation in the protease-rich extracellular environment. Therefore, tFNA provides a delivery vehicle for AMPs targeting a broad range of disease.
a b s t r a c tHomocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE À/À mice fed high-methionine diet for 20 weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The upregulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.
An aqueous electrochemically mediated atom transfer radical polymerization (eATRP) was performed in a small volume solution (75 μL) deposited on a screen-printed electrode (SPE). The reaction was open to air, thanks to the use of glucose oxidase (GOx) as an oxygen scavenger. Welldefined poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA), and corresponding DNA−polymer biohybrids were synthesized by the small-volume eATRP at room temperature. The reactions were simplified and polymerization rates increased by the application of the enzyme deoxygenating system and the compact electrochemical setup. Importantly, the volume of polymerization mixture was lowered to microliters, which not only decreases the cost for each reaction, but can also be potentially implemented in combinatorial chemistry and electrode-array configurations for high-throughput systems.
Aims: To understand the effects of Trp residues in linear antimicrobial peptides with a-helical conformations on cell permeation ability and membrane transduction efficacy. Methods and Results: A series of L-K6 analogues were designed and synthesized by replacing Ile or Leu with Trp at different positions on the hydrophobic face of L-K6. The antimicrobial and haemolytic activity and secondary structure of the designed Trp-containing peptides were assessed. In addition, the role of Trp in membrane disruption for these designed peptides was investigated. I1W, I4W and L5W demonstrated stronger activity than the other peptides against both Gram-positive and Gram-negative bacteria. All of the tested peptides preferentially interacted with negatively charged vesicles composed of phosphatidylglycerol (PG)/cardiolipin (CL) or PG/CL/phosphatidylethanolamine, and, to a lesser extent, with zwitterionic vesicles. I1W, I4W and L5W caused calcein release at 2Á5 lmol l À1 . Conclusions:The position of Trp, rather than the number of Trp residues, in these peptides was an important factor in the antimicrobial activity. Trp residues were deeply inserted into negatively charged membranes but were largely exposed in aqueous buffer solution.Significance and Impact of the Study: These Trp-containing peptides may represent good candidates for new antibiotic agents and for use in new therapeutic approaches.
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