The inhibitory effect of the combination of two new peptides on biofilm formation by Acinetobacter baumannii.

The emergence of extensively drug-resistant (XDR) Acinetobacter baumannii strains and the limited number of efficacious antibiotics demonstrate an urgent need to develop novel agents to treat infections caused by this dangerous pathogen. To find antimicrobial peptides against A. baumannii growing either in planktonic or in biofilm mode, biopanning was carried out with a peptide library on five XDR A. baumannii strains grown in the medium containing human blood (blood biopanning) and biofilms formed by these strains (biofilm biopanning). Two groups of peptides were identified, among which two peptides N10 (from blood biopanning) and NB2 (from biofilm biopanning) were selected and synthesized for more assessments. The selected peptides showed significant binding to A. baumannii rather than to the human cell line Caco-2. Both peptides were effective against A. baumannii and showed antibacterial activities (minimum inhibitory concentration (MIC) 500 µg/ml). In the biofilm inhibition assay, NB2 reduced biofilm more efficiently (75%) than N10 (50%). The combination of the two peptides could function better than each peptide alone to prevent biofilm formation by A. baumannii. Supplementation of conventional therapy with a mixture of peptides targeting A. baumannii or using peptides to deliver antibiotics specifically to the site of infection may be promising to control A. baumannii-related diseases.

Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets.

Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.

A systems medicine approach for finding target proteins affecting treatment outcomes in patients with non-Hodgkin lymphoma.

Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively. PR- and PS-specific hubs were evaluated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. The PR-specific hubs were involved in Wnt SP, signaling by Notch1 in cancer, telomere maintenance, and transcriptional misregulation. In contrast, glutamate receptor SP, Fc receptor-related pathways, growth factors-related SPs, and Wnt SP were statistically significant enriched pathways, based on the pathway analysis of PS hubs. The results revealed that the most PR-specific proteins were associated with events involved in tumor development, while chemotherapy in the PS group was associated with side effects of drugs and/or cancer recurrence. As the findings demonstrated, PR- and PS-specific proteins in this study can be promising therapeutic targets in future studies.