Substitution of lysine for isoleucine at the center of the nonpolar face of the antimicrobial peptide, piscidin-1, leads to an increase in the rapidity of bactericidal activity and a reduction in toxicity.

Purpose: Piscidin-1 is an effective antimicrobial peptide (AMP) against a variety of microbes. However, its toxicity has been reported as a limitation for its potential therapeutic applications. The toxicity of piscidin-1 may be related to the long nonpolar face of this AMP. Here, we investigated different piscidin-1 analogs to reach a peptide with the reduced toxicity. Material and methods: In vitro and in vivo antibacterial activity and toxicity of piscidin-1 analogs generated by replacement of isoleucine at the border (I9) or the center (I16) of the nonpolar face of piscidin-1 by alanine or lysine were investigated. Results: The results indicated that among all peptides, piscidin-1 with the highest HPLC retention time (RT) and I16K-piscidin-1 with the lowest RT had the highest and lowest cytotoxicity, respectively. Although I16K-piscidin-1 possessed the same MIC value as the parent peptide (piscidin-1) and other analogs, I16K-piscidin-1 exhibited a higher rapidity of bactericidal action at 5×MIC. The ß-galactosidase leakage and propidium iodide staining assays indicated a higher pore-forming capacity of I16K-piscidin-1 relative to the parent peptide (piscidin-1). Taken together, RT is suggested to have a direct association with the toxicity and an inverse association with the rapidity of bactericidal action and pore-forming capacity. After infection of mice with clinical colistin-resistant Acinetobacter baumannii or clinical methicillin-resistant Staphylococcus aureus strains, treatment with I16K-piscidin-1, but not piscidin-1 and other analogs, resulted in a significantly stronger bactericidal potency. Furthermore, I16K-piscidin-1 exhibited the lowest in vivo toxicity.  Conclusion: Overall, in vitro and in vivo comparison of piscidin-1 and its analogs together documented that replacement of isoleucine at the center of the nonpolar face of piscidin-1(I16) by lysine leads to not only a decrease in toxicity potential but also an increase in bactericidal potential.

Effects of Intermittent Fasting during Ramadan on Insulin-like Growth Factor-1, Interleukin 2, and Lipid Profile in Healthy Muslims.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) and interleukin-2 (IL-2) play an essential role in pathophysiology of several chronic diseases. As a stressor, fasting in Ramadan may increase inflammatory markers such as IGF-1 and IL-2 in Muslims. The aim of this before-after study was to investigate the effects of fasting in Ramadan on IGF-1 and IL-2 levels in individuals. METHODS: In all, 34 men age 16-64 years were selected out of the overall number of individuals who were ready for fasting entirely throughout Ramadan. A sample of blood was drawn from the contributors before and after Ramadan, and plasma IGF-1, IL-2, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined. To identify differences between the initial and final values of test results of the study for plasma IGF-1, IL-2, and lipid parameters, we used paired sample T-test. RESULTS: Paired sample T-test illustrated a significant decrease in IGF-1 and IL-2 levels after Ramadan fasting compared to before Ramadan. The concentration of TG, cholesterol, and LDL-C levels underwent significant decreases over the period of the study. HDL-C levels did not change significantly during the study. A significant decrease in weight, waist circumferences, calorie, carbohydrate, and fat intake were observed in participants during Ramadan fasting. CONCLUSIONS: It is concluded that fasting in Ramadan independent of anthropometric measures attenuates inflammation and is beneficiary to health.