Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form alpha-helices or beta-sheet-like structures that can insert into and subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core-shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood-brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.
The present study was conducted to explore the mechanisms leading to differences among fishes in the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFAs). Replacement of fish oil with vegetable oil caused varied degrees of increase in 18-carbon fatty acid content and decrease in n-3 LC-PUFA content in the muscle and liver of rainbow trout (Oncorhynchus mykiss), Japanese seabass (Lateolabrax japonicus) and large yellow croaker (Larimichthys crocea), suggesting that these fishes have differing abilities to biosynthesize LC-PUFAs. Fish oil replacement also led to significantly up-regulated expression of FADS2 and SREBP-1 but different responses of the two PPAR-α homologues in the livers of these three fishes. An in vitro experiment indicated that the basic transcription activity of the FADS2 promoter was significantly higher in rainbow trout than in Japanese seabass or large yellow croaker, which was consistent with their LC-PUFA biosynthetic abilities. In addition, SREBP-1 and PPAR-α up-regulated FADS2 promoter activity. These regulatory effects varied considerably between SREBP-1 and PPAR-α, as well as among the three fishes. Taken together, the differences in regulatory activities of the two transcription factors targeting FADS2 may be responsible for the different LC-PUFA biosynthetic abilities in these three fishes that have adapted to different ambient salinity.
Although antimicrobial
peptides (AMPs) hold tremendous promise
in overcoming the threats of multidrug resistance, the main obstacle
to successful therapeutic applications is their poor stability. Various
synthetic strategies such as unnatural amino acids and chemical modifications
have made advances for improving this problem. However, this complicated
synthesis often greatly increases the cost of production. Here, we
show that a series of novel peptides, designed by combining an α-helical
coiled coil model, knowledge of the specificity of proteolysis and
major parameters of AMPs, exhibited efficient activity against all
tested Gram-negative bacteria under acidic condition and demonstrate
low toxicity. Of these α-helical coiled coil peptides, 3IH3
displayed the highest average therapeutic index (GMTI =
294.25) with high stability toward salts, serum, extreme pH, heat,
and proteases. Electron microscopy and biological analytical technique
analyses showed that 3IH3 killed bacterial cells via a multicomplementary
mechanism at pH 6.0, with physical membrane disruption as the dominant
bactericidal mechanism. These results suggest that 3IH3 shows great
stability as an inexpensive and effective antimicrobial activity agent
and has the potential for clinical application in the treatment of
infections occurring in body sites with acidic pH.
Six equal‐protein and equal‐lipid diets were formulated: the fish meal (FM) diet, the soya bean meal (SBM) diet with 40% of FM protein replaced by SBM protein and tributyrin (TB) diets with 0.05% (TB0.05), 0.10% (TB0.1), 0.20% (TB0.2) and 0.40% (TB0.4) tributyrin supplemented in the SBM‐based diet. Each kind of diet was randomly fed to triplicate tanks with 20 fish per tank. Fish were fed apparent satiation twice daily for 56 days. No significant difference in weight gain rate (WGR) and feed efficiency rate (FER) was observed between fish fed the FM, TB0.1 and TB0.2 diets (p > .05). Muscle histidine and arginine proportion of fish fed TB0.1 diet was significantly higher than that of fish fed the SBM diet (p < .05). Intestine morphology results indicated that the supplementation of 0.1% tributyrin significantly improved the mucosal fold height, microvilli length and microvilli density when compared with those of fish fed the SBM diet (p < .05). The supplementation of dietary tributyrin suppressed the pro‐inflammatory gene expression, which may be due to the improvement of physical barrier and modification of microbial communities, such as Acinetobacter, Rhodocyclaceae, Brevundimonas, Sphingopyxis, Hydrogenophaga, Methyloversatilis and Devosia. In conclusion, dietary 0.1% tributyrin supplementation in high‐soya bean meal diet improved growth performance, flesh quality and intestinal morphology structure integrity of yellow drum.
Recent developments in nanotechnology promoted the production of nanomaterials with various shapes and sizes by utilizing interdisciplinary researches of biology, chemistry, and material science toward the clinical perspectives. In particular, gold and silver (Ag) are noble metals that exhibit tunable and unique plasmonic properties for the downstream applications. Ag exhibits higher thermal and electrical conductivities, and more efficient in the electron transfer than gold with sharper extinction bands. In addition, modified Ag nanoparticle is more stable in water and air. With all these above features, Ag is an attractive tool in various fields, including diagnosis, drug delivery, environmental, electronics, and as antimicrobial agent. In particular, applications of Ag nanoparticle in the fields of biosensor and imaging are prominent in recent days. Enhancing the specific detection of clinical markers with Ag nanoparticle has been proved by several studies. This review discussed the constructive application of Ag nanoparticle in biosensor and bioimaging for the detection of small molecule to larger whole cell in the perspectives of diagnosing diseases.
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