Helicobacterpylori is one of the most prevalent pathogens colonizing 50% of the world’s population and causing gastritis and gastric cancer. Even with triple and quadruple antibiotic therapies, H. pylori shows increased prevalence of resistance to conventional antibiotics and treatment failure. Due to their pore-forming activity, antimicrobial peptides (AMP) are considered as a good alternative to conventional antibiotics, particularly in the case of resistant bacteria. In this study, temporin-SHa (a frog AMP) and its analogs obtained by Gly to Ala substitutions were tested against H. pylori. Results showed differences in the antibacterial activity and toxicity of the peptides in relation to the number and position of D-Ala substitution. Temporin-SHa and its analog NST1 were identified as the best molecules, both peptides being active on clinical resistant strains, killing 90–100% of bacteria in less than 1 h and showing low to no toxicity against human gastric cells and tissue. Importantly, the presence of gastric mucins did not prevent the antibacterial effect of temporin-SHa and NST1, NST1 being in addition resistant to pepsin. Taken together, our results demonstrated that temporin-SHa and its analog NST1 could be considered as potential candidates to treat H. pylori, particularly in the case of resistant strains.
The goal of this study was to compare the effects of Bacillus subtilis and the antibiotic enrofloxacin on growth performance, immune response, intestinal histomorphometry and cecal Salmonella numbers in broilers challenged with S. gallinarum. Salmonella-free chicks (n = 240) were allocated to four groups, comprising six replicates (n = 10) each. Group NN was not infected and received no treatment. Group SN was infected with Salmonella and received no treatment. Group SE was infected with Salmonella and treated with the antibiotic enrofloxacin. Group SP was infected with Salmonella and treated orally with the probiotic B. subtilis. Initially the groups that were infected with Salmonella had reduced growth performance compared with NN. By the fourth week, SE and SP had recovered and weighed as much as or more than NN. The SP group had greater cellular immunity and relative weights of the bursa and thymus than the other groups. SN had the lowest villus height in all the segments of the small intestine and a larger Salmonella population in the ceca. Probiotic supplementation reduced the pathological outcomes more than enrofloxacin. Prophylactic use of B. subtilis-type probiotics had similar effects to the use of antibiotics, alleviated the stress related to infection of S. gallinarum, and improved the growth performance, immune function, and gut mucosal development in broilers. Keywords: growth promoters, immunity, probiotics, poultry villi length
Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur4-2-Nal3-Ala2-Phe1-CONH2) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC50 = 0.15 ± 0.05 µg/mL or 0.28 +/− 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, 1H- NMR, 13C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.
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