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Ravichandran N. Murugan Binu Jacob Mija Ahn Eunha Hwang Hoik Sohn Hyo-Nam Park Eunjung Lee Ji-Hyung Seo Chaejoon Cheong Ky-Youb Nam Jae-Kyung Hyun Ki-Woong Jeong Yangmee Kim Song Yub Shin Jeong Kyu Bang 《PloS one》2013,8(11)
Background
Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability.Methodology/Principal Findings
In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes.Conclusion/Significance
The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics. 相似文献73.
Travis B. Conley George P. McCabe Eunjung Lim Kevin E. Yarasheski Craig A. Johnson Wayne W. Campbell 《The Journal of nutritional biochemistry》2013,24(4):693-699
Research suggests that changes in leucine oxidation (leuox) with feeding may reflect adult protein requirements. We evaluated this possibility by assessing the effects of age, sex, and different protein intakes on whole-body leucine kinetics and nitrogen balance. Thirty-four young (n= 18, 22–46 years) and old (n= 16, 63–81 years) men and women completed three 18-day trials with protein intakes of 0.50, 0.75 and 1.00 g protein·kg body weight? 1·d? 1. Fasting and fed-state leucine kinetics were quantified on day 12 of each trial using a primed, constant infusion of L-[1-13C]leucine. Protein requirement was estimated using classical nitrogen balance measurements and calculations. Leucine kinetics parameters were influenced by age and sex across all protein intakes. With feeding, leuox increased more in old vs. young adults. Independent of age, fasting and fed-state leuox were lower, and net leucine balance (fasting+fed-state) was higher in women vs. men. Among all subjects and protein intakes, nitrogen balance was correlated with fed-state leuox (r= 0.39), fed-state leucine balance (r= 0.60), net leucine balance (r= 0.49) and the change in leuox from the fasting to fed state (r= 0.49) (P<.05 for all results). At the highest protein intake, the change in leuox with feeding was inversely correlated with protein requirement (r=?0.39). These findings indicate that leucine kinetics, especially leuox, reflect nitrogen balance-based estimates of the need for dietary protein and generally support the view that protein requirement is comparable between young and old adults. 相似文献
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Junwon Kim Jeongjin Kwon Doohyun Lee Suyeon Jo Dong-Sik Park Jihyun Choi Eunjung Park Jong Yeon Hwang Yoonae Ko Inhee Choi Moon Kyeong Ju JiYe Ahn Junghwan Kim Sung-Jun Han Tae-Hee Kim Jonathan Cechetto Jiyoun Nam Sujin Ahn Jinhwa Lee 《Bioorganic & medicinal chemistry letters》2013,23(1):153-157
We identified a novel class of triazolothienopyrimidine (TTPM) compounds as potent HIV-1 replication inhibitors during a high-throughput screening campaign that evaluated more than 200,000 compounds using a cell-based full replication assay. Herein, we report the optimization of the antiviral activity in a cell-based assay system leading to the discovery of aryl-substituted TTPM derivatives (38, 44, and 45), which exhibited significant inhibition of HIV-1 replication with acceptable safety margins. These novel and potent TTPMs could serve as leads for further development. 相似文献
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Xiu Zhou Xiao-Yi Zeng Hao Wang Songpei Li Eunjung Jo Charlie C. L. Xue Minjia Tan Juan C. Molero Ji-Ming Ye 《PloS one》2014,9(9)
Our recent study (referred as Study 1) showed that the triterpenoid oleanolic acid (OA) was able to produce a sustained correction of hyperglycemia beyond treatment period in type 2 diabetes (T2D) mice with liver as a responsible site. To follow up the previous observations, the present study (referred as Study 2) investigated the possible role of acetylation of FoxO1 and associated events in this therapeutic memory by characterizing the pathways regulating the acetylation status during and post-OA treatments. OA treatment (100 mg/kg/day for 4 weeks, during OA treatment) reduced hyperglycemia in T2D mice by ∼87% and this effect was largely (∼70%) maintained even 4 weeks after the cessation of OA administration (post-OA treatment). During OA treatment, the acetylation and phosphorylation of FoxO1 were markedly increased (1.5 to 2.5-fold) while G6Pase expression was suppressed by ∼80%. Consistent with this, OA treatment reversed pyruvate intolerance in high-fat fed mice. Histone acetyltransferase 1 (HAT1) content was increased (>50%) and histone deacetylases (HDACs) 4 and 5 (not HDAC1) were reduced by 30–50%. The OA-induced changes in FoxO1, G6Pase, HAT1 and HDACs persisted during the post-OA treatment period when the increased phosphorylation of AMPK, SIRT1 content and reduced liver triglyceride had subsided. These results confirmed the ability of OA to control hyperglycemia far beyond treatment period in T2D mice. Most importantly, in the present study we demonstrated acetylation of FoxO1 in the liver is involved in OA-induced memory for the control of hyperglycemia. Our novel findings suggest that acetylation of the key regulatory proteins of hepatic gluconeogenesis is a plausible mechanism by the triterpenoid to achieve a sustained glycemic control for T2D. 相似文献
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Kim E Youn B Kemper L Campbell C Milting H Varsanyi M Kang C 《Journal of molecular biology》2007,373(4):1047-1057
Mutations of conserved residues of human cardiac calsequestrin (hCSQ2), a high-capacity, low-affinity Ca2+-binding protein in the sarcoplasmic reticulum, have been associated with catecholamine-induced polymorphic ventricular tachycardia (CPVT). In order to understand the molecular mechanism and pathophysiological link between these CPVT-related missense mutations of hCSQ2 and the resulting arrhythmias, we generated three CPVT-causing mutants of hCSQ2 (R33Q, L167H, and D307H) and two non-pathological mutants (T66A and V76M) and investigated the effect of these mutations. In addition, we determined the crystal structure of the corresponding wild-type hCSQ2 to gain insight into the structural effects of those mutations. Our data show clearly that all three CPVT-related mutations lead to significant reduction in Ca2+-binding capacity in spite of the similarity of their secondary structures to that of the wild-type hCSQ2. Light-scattering experiments indicate that the Ca2+-dependent monomer-polymer transitions of the mutants are quite different, confirming that the linear polymerization behavior of CSQ is linked directly to its high-capacity Ca2+ binding. R33Q and D307H mutations result in a monomer that appears to be unable to form a properly oriented dimer. On the other hand, the L167H mutant has a disrupted hydrophobic core in domain II, resulting in high molecular aggregates, which cannot respond to Ca2+. Although one of the non-pathological mutants, T66A, shares characteristics with the wild-type, the other null mutant, V76M, shows significantly altered Ca2+-binding and polymerization behaviors, calling for careful reconsideration of its status. 相似文献
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Sungbea Ban Nam Hyun Cho Eunjung Min Jung Kweon Bae Yujin Ahn Sungwon Shin Soo‐Ah Park Yoonsung Lee Woonggyu Jung 《Journal of biophotonics》2019,12(7)
Recent progress in three‐dimensional optical imaging techniques allows visualization of many comprehensive biological specimens. Optical clearing methods provide volumetric and quantitative information by overcoming the limited depth of light due to scattering. However, current imaging technologies mostly rely on the synthetic or genetic fluorescent labels, thus limits its application to whole‐body visualization of generic mouse models. Here, we report a label‐free optical projection tomography (LF‐OPT) technique for quantitative whole mouse embryo imaging. LF‐OPT is based on the attenuation contrast of light rather than fluorescence, and it utilizes projection imaging technique similar to computed tomography for visualizing the volumetric structure. We demonstrate this with a collection of mouse embryo morphologies in different stages using LF‐OPT. Additionally, we extract quantitative organ information applicable toward high‐throughput phenotype screening. Our results indicate that LF‐OPT can provide multi‐scale morphological information in various tissues including bone, which can be difficult in conventional optical imaging technique. 相似文献
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