Design of Proteolytic-Resistant Antifungal Peptides by Utilizing Minimum d-Amino Acid Ratios.

Antifungal peptides are an appealing alternative to standard antifungal medicines due to their unique mechanism of action and low-level resistance. However, their susceptibility to protease degradation keeps hindering their future development. Herein, a library was established to design peptides with protease resistance and high antifungal activity. The peptides were incorporated with minimal D-amino acids to further improve the protease stability. The most active peptide, IR3, demonstrated good antifungal activity and low toxicity, and its molecular integrity was maintained after protease hydrolysis for 8 h at 2 mg/mL. Furthermore, IR3 could permeate the fungal cell wall, disrupt the cell membrane, produce reactive oxygen species, and induce apoptosis in fungal cells. In vivo experiments confirmed that IR3 could effectively treat fungal keratitis. Collectively, these findings suggest that IR3 is a promising antifungal agent and may be beneficial in the design and development of protease-resistant antifungal peptides.

Energy and Arginine Density in the Diets of Arbor Acre Hens from 40 to 50 Weeks of Age: Effects on Development and Lipid Metabolism of Embryos.

The effects of maternal dietary energy and arginine level on embryonic development and serum lipid metabolism were investigated in this study. A 2 × 3 factorial experiment was conducted with six treatments represented by 10 replicates of eight Arbor Acre broiler breeder hens each. Diets fed from 40 to 50 weeks of age were formulated to contain two digestible arginine levels (9.6 g/kg and 14.5 g/kg) and three metabolic energy levels (10.08 MJ ME/kg, 11.88 MJ ME/kg, and 13.68 MJ ME/kg). Artificial insemination was used, and eggs collected from 50 weeks of hens' age were hatched. Embryonic growth, biochemical and endocrine indexes of embryonic serum and allantoic fluid were measured on different embryonic days (E). The results were as follows: Egg weight (E0, E11, E13) and embryonic weight (E12, E15) in the high-energy group (13.68 MJ ME/kg) were significantly decreased (p < 0.01), as were embryonic breast rate (E13, E15, E21), thigh rate (E13-E21) and liver rate (E15-E21). The reciprocal effects of arginine and energy were significant on breast rate (E11, E13, E17), thigh rate (E19, E21) and liver rate (E11, E19) of the embryo (p < 0.05). CHO (E13-E19), high-density lipoprotein (E13, E15, E21), low-density lipoprotein (E15, E19, E21), and blood glucose (E13) levels in embryonic serum decreased with the increase in maternal dietary energy level (p < 0.05), but triglyceride levels (E19, E21) showed the opposite result (p < 0.05). The levels of cholesterol and blood glucose in embryonic serum at E11 and urea nitrogen in allantoic fluid at E11-E15 were significantly decreased in the 14.5 g/kg arginine group (p < 0.01). With the increase in maternal dietary energy and arginine levels, embryonic serum nitric oxide synthases levels (E11, E15, E19) increased significantly (p < 0.01). The reciprocal effect of arginine and energy in maternal diets was significant on the embryonic serum high-density lipoprotein level at E21 (p < 0.05). Embryonic serum insulin levels at E13 were significantly elevated in the high-energy group (13.68 MJ ME/kg). The reciprocal effect of arginine and energy was significant on the embryonic serum growth hormone level (p < 0.01). Embryonic serum growth hormone levels were significantly reduced in the 14.5 g/kg arginine and 13.68 MJ/kg metabolic energy group (p < 0.01). In conclusion, maternal restricted feeding improved embryonic development and regulated lipid metabolism-related indices in embryonic serum. Maternal dietary addition of digestible arginine had a significant effect on lipid metabolism indices in embryos. There was a maternal effect of maternal dietary energy and arginine levels on embryo growth and development. The deposition of maternal nutrients affects the development of embryos.

Dietary supplementation of l-arginine and chromium picolinate in sows during gestation affects the muscle fibre characteristics but not the performance of their progeny.

BACKGROUND: The present study investigated the effects of dietary supplementation of l-arginine and chromium picolinate (CrP) in sows during gestation on muscle fibre characteristics, performance and carcass characteristics of their progeny. Sixty healthy sows were randomly divided into four groups as a 2 × 2 factorial experiment design: one group received the control diet, another received the control diet + 10 g kg-1 l-arginine, the third group received the control diet + 400 ppb CrP, and the fourth group received the control diet + 10 g kg-1 l-arginine and 400 ppb CrP. RESULTS: The results showed that sows fed the diet supplemented with CrP produced progeny with higher muscle fibre numbers at birth, weaning and slaughter compared to sows fed the control diet. For mean fibre areas, the same result was found at weaning. For progeny of sows fed diets supplemented with l-arginine, only higher muscle fibre numbers at slaughter was observed. Almost no differences were observed regarding average daily gains, average daily feed intake, gain-to-feed ratios, carcass and meat traits. CONCLUSION: The results of the present study indicate that dietary supplementation of l-arginine and particularly CrP in sows during gestation alters muscle fibre numbers in their offspring, although not their performance or carcass characteristics. © 2017 Society of Chemical Industry.

Characterization of cell selectivity, physiological stability and endotoxin neutralization capabilities of α-helix-based peptide amphiphiles.

While naturally occurring antimicrobial peptides (AMPs) have been of increasing interest as alternative antibiotics due to their broad-spectrum antimicrobial activity and reduced possibility for the development of bacterial drug-resistance, some concerns such as potential cytotoxicity, poor antimicrobial activity and weak physiological stability may ultimately weaken their development as antimicrobial agents. To generate AMPs with enhanced therapeutic potential, we designed α-helical hybrid peptides based on PRW4, Fowlicidin-2, Protegrin-3 and Tritrpticin sequences to gain insights into their selectivities, physiological stabilities and endotoxin neutralization capabilities. The designed hybrid peptides PR-FO, PR-PG and PR-TR exhibited high cell selectivity towards bacterial cells over human red blood cells (hRBCs). Their activities were maintained in the presence of physiological concentrations of salts or serum, indicating a high stability in vitro. The results from fluorescence spectroscopy, flow cytometry, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that these designed peptides killed microbial cells by increasing membrane permeability and damaging membrane envelope integrity. Moreover, the hybrid peptides effectively neutralized endotoxins while causing minimal cytotoxicities. Collectively, our results suggest that these hybrid peptides, in particular PR-FO, have tremendous potential for use as novel antimicrobial and antisepsis agents.