The growing problem of antibiotic-resistant microorganisms results in an urgent need for substitutes to conventional antibiotics with novel modes of action and effective activities. Antimicrobial peptides (AMPs), produced by a wide variety of living organisms acting as a defense mechanism against invading pathogenic microbes, are considered to be such promising alternatives. AMPs display a broad spectrum of antimicrobial activity and a low propensity for developing resistance. Therefore, a thorough understanding of AMPs is essential to exploit them as antimicrobial drugs. Considering this, we developed a comprehensive user-friendly data repository of antimicrobial peptides (DRAMP), which holds 17349 antimicrobial sequences, including 4571 general AMPs, 12704 patented sequences and 74 peptides in drug development. Entries in the database have detailed annotations, especially detailed antimicrobial activity data (shown as target organism with MIC value) and structure information. Annotations also include accession numbers crosslinking to Pubmed, Swiss-prot and Protein Data Bank (PDB). The website of the database comes with easy-to-operate browsing as well as searching with sorting and filtering functionalities. Several useful sequence analysis tools are provided, including similarity search, sequence alignment and conserved domain search (CD-Search). DRAMP should be a useful resource for the development of novel antimicrobial peptide drugs.
BackgroundThe serious consequences of diabetes mellitus, and the subsequent economic burden, call for urgent preventative action in developing countries. This study explores the clinical and economic outcomes of strategies that could potentially prevent diabetes based on Chinese circumstances. It aims to provide indicators for the long-term allocation of healthcare resources for authorities in developing countries.MethodsA representative sample of Chinese adults was used to create a simulated population of 20,000 people aged 25 years and above. The hybrid decision tree Markov model was developed to compare the long-term clinical and economic outcomes of four simulated diabetes prevention strategies with a control group, where no prevention applied. These preventive strategies were the following: (i) one-off screening for undiagnosed diabetes and impaired glucose tolerance (IGT), with lifestyle interventions on diet, (ii) on exercise, (iii) on diet combined exercise (duo-intervention) respectively in those with IGT, and (iv) one-off screening alone. Independent age-specific models were simulated based on diverse incidences of diabetes, mortalities and health utilities. The reported outcomes were the following: the remaining survival years, the quality-adjusted life years (QALYs) per diabetes or IGT subjects, societal costs per simulated subject and the comparisons between preventions and control over 40 years. Sensitivity analyses were performed based on variations of all assumptions, in addition to the performance and the compliance of screening.ResultsCompared with the control group, all simulated screening programmes prolonged life expectancy at the initiation ages of 25 and 40 years, postponed the onset of diabetes and increased QALYs at every initiation age. Along with an assumption of six years intervention, prevention programmes were associated with cost-saving compared with the control group, especially in the population aged 25 years. The savings were at least US$2017 per subject, but no statistically significant difference was observed among the intervention strategies within each age groups. The cost savings were reduced when screening was affected by poor performance and noncompliance.ConclusionsDeveloping countries have few effective strategies to manage the prevention of diabetes. One-off screening for undiagnosed diabetes and IGT, with appropriate lifestyle interventions for those with IGT are cost saving in China, especially in young adults.
Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immune system, protect against pathogens including bacteria, fungi, viruses, and parasites. In general, AMPs are relatively small peptides (<10 kDa) with cationic nature and amphipathic structure and have modes of action different from traditional antibiotics. Up to now, there are more than 19 000 AMPs that have been reported, including those isolated from nature sources or by synthesis. They have been considered to be promising substitutes of conventional antibiotics in the quest to address the increasing occurrence of antibiotic resistance. However, most AMPs have modest direct antimicrobial activity, and their mechanisms of action, as well as their structure-activity relationships, are still poorly understood. Computational strategies are invaluable assets to provide insight into the activity of AMPs and thus exploit their potential as a new generation of antimicrobials. This article reviews the advances of AMP databases and computational tools for the prediction and design of new active AMPs. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic-based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non-cancerous renal tissues using label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins. Among 3,061 identified non-redundant proteins, we found that 210 proteins were differentially expressed (83 overexpressed and 127 underexpressed) in ccRCC tissue when compared with normal kidney tissues. Two most significantly dysregulated proteins (PCK1 and SNRPF) were chosen to be confirmed by western blotting. Pathway analysis of 210 differentially expressed proteins showed that dysregulated proteins are related to many cancer-related biological processes such as oxidative phosphorylation, glycolysis and amino acid synthetic pathways. Online survival analysis indicated the prognostic value of these dysregulated proteins. In conclusion, we identified some potential diagnostic biomarkers for ccRCC and an in-depth understanding of their involved biological pathways may help pave the way to discover new therapeutic strategies for ccRCC.
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