Fighting multidrug resistance with a fruit extract: anti-cancer and anti-biofilm activities of Acca sellowiana.

In this study, the efficacy of Acca sellowiana fruit acetonic extract on human MDR cancer cells was tested for the first time, and it was demonstrated that the fruit extract is effective on both sensitive and resistant tumor cells. The effects of A. sellowiana extract on bacterial biofilm were also examined for the first time. By crystal violet assays and confocal microscopy analyses, it was demonstrated that the plant extract is able to strongly inhibit biofilm formation of both sensitive and resistant bacterial strains. Furthermore, antimicrobial activity assays and TEM analyses clearly demonstrated the effectiveness of plant extract on planktonic bacterial cells in both sensitive and resistant strains. Altogether, these findings intriguingly expand the panel of activities of A. sellowiana fruit extract with respect to previous reports, and open interesting perspectives to its therapeutic applications.

Hybrid 18F-FDG-PET/MRI Measurement of Standardized Uptake Value Coupled with Yin Yang 1 Signature in Metastatic Breast Cancer. A Preliminary Study.

PURPOSE: Detection of breast cancer (BC) metastasis at the early stage is important for the assessment of BC progression status. Image analysis represents a valuable tool for the management of oncological patients. Our preliminary study combined imaging parameters from hybrid 18F-FDG-PET/MRI and the expression level of the transcriptional factor Yin Yang 1 (YY1) for the detection of early metastases. METHODS: The study enrolled suspected n = 217 BC patients that underwent 18F-FDG-PET/MRI scans. The analysis retrospectively included n = 55 subjects. n = 40 were BC patients and n = 15 imaging-negative female individuals were healthy subjects (HS). Standard radiomics parameters were extracted from PET/MRI image. RNA was obtained from peripheral blood mononuclear cells and YY1 expression level was evaluated by real time reverse transcription polymerase chain reactions (qRT-PCR). An enzyme-linked immuosorbent assay (ELISA) was used to determine the amount of YY1 serum protein. Statistical comparison between subgroups was evaluated by Mann-Whitney U and Spearman's tests. RESULTS: Radiomics showed a significant positive correlation between Greg-level co-occurrence matrix (GLCM) and standardized uptake value maximum (SUVmax) (r = 0.8 and r = 0.8 respectively) in BC patients. YY1 level was significant overexpressed in estrogen receptor (ER)-positive/progesteron receptor-positive/human epidermal growth factor receptor2-negative (ER+/PR+/HER2-) subtype of BC patients with synchronous metastasis (SM) at primary diagnosis compared to metachronous metastasis (MM) and HS (p < 0.001) and correlating significantly with 18F-FDG-uptake parameter (SUVmax) (r = 0.48). CONCLUSIONS: The combination of functional 18F-FDG-PET/MRI parameters and molecular determination of YY1 could represent a novel integrated approach to predict synchronous metastatic disease with more accuracy than 18F-FDG-PET/MRI alone.

Antimicrobial potency of cationic antimicrobial peptides can be predicted from their amino acid composition: Application to the detection of "cryptic" antimicrobial peptides.

Cationic antimicrobial peptides (CAMPs) are essential components of innate immunity. Here we show that antimicrobial potency of CAMPs is linearly correlated to the product CmHnL where C is the net charge of the peptide, H is a measure of its hydrophobicity and L its length. Exponents m and n define the relative contribution of charge and hydrophobicity to the antimicrobial potency. Very interestingly the values of m and n are strain specific. The ratio n/(m+n) can vary between ca. 0.5 and 1, thus indicating that some strains are sensitive to highly charged peptides, whereas others are particularly susceptible to more hydrophobic peptides. The slope of the regression line describing the correlation "antimicrobial potency"/"CmHnL product" changes from strain to strain indicating that some strains acquired a higher resistance to CAMPs than others. Our analysis provides also an effective computational strategy to identify CAMPs included inside the structure of larger proteins or precursors, which can be defined as "cryptic" CAMPs. We demonstrate that it is not only possible to identify and locate with very good precision the position of cryptic peptides, but also to analyze the internal structure of long CAMPs, thus allowing to draw an accurate map of the molecular determinants of their antimicrobial activity. A spreadsheet, provided in the Supplementary material, allows performing the analysis of protein sequences. Our strategy is also well suited to analyze large pools of sequences, thus significantly improving the identification of new CAMPs and the study of innate immunity.

Novel human bioactive peptides identified in Apolipoprotein B: Evaluation of their therapeutic potential.

Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their anti-infective properties are mainly due to their ability to modulate the immune response. Here, we report the recombinant production and characterization of two novel HDPs identified in human Apolipoprotein B (residues 887-922) by using a bioinformatics method recently developed by our group. We focused our attention on two variants of the identified HDP, here named r(P)ApoBL and r(P)ApoBS, 38- and 26-residue long, respectively. Both HDPs were found to be endowed with a broad-spectrum antimicrobial activity while they show neither toxic nor haemolytic effects towards eukaryotic cells. Interestingly, both HDPs were found to display a significant anti-biofilm activity, and to act in synergy with either commonly used antibiotics or EDTA. The latter was selected for its ability to affect bacterial outer membrane permeability, and to sensitize bacteria to several antibiotics. Circular dichroism analyses showed that SDS, TFE, and LPS significantly alter r(P)ApoBL conformation, whereas slighter or no significant effects were detected in the case of r(P)ApoBS peptide. Interestingly, both ApoB derived peptides were found to elicit anti-inflammatory effects, being able to mitigate the production of pro-inflammatory interleukin-6 and nitric oxide in LPS induced murine macrophages. It should also be emphasized that r(P)ApoBL peptide was found to play a role in human keratinocytes wound closure in vitro. Altogether, these findings open interesting perspectives on the therapeutic use of the herein identified HDPs.