The plant-derived decapeptide OSIP108 interferes with Candida albicans biofilm formation without affecting cell viability

We previously identified a decapeptide from the model plant Arabidopsis thaliana, OSIP108, which is induced upon fungal pathogen infection. In this study, we demonstrated that OSIP108 interferes with biofilm formation of the fungal pathogen Candida albicans without affecting the viability or growth of C. albicans cells. OSIP108 displayed no cytotoxicity against various human cell lines. Furthermore, OSIP108 enhanced the activity of the antifungal agents amphotericin B and caspofungin in vitro and in vivo in a Caenorhabditis elegans-C. albicans biofilm infection model. These data point to the potential use of OSIP108 in combination therapy with conventional antifungal agents. In a first attempt to unravel its mode of action, we screened a library of 137 homozygous C. albicans mutants, affected in genes encoding cell wall proteins or transcription factors important for biofilm formation, for altered OSIP108 sensitivity. We identified 9 OSIP108-tolerant C. albicans mutants that were defective in either components important for cell wall integrity or the yeast-to-hypha transition. In line with these findings, we demonstrated that OSIP108 activates the C. albicans cell wall integrity pathway and that its antibiofilm activity can be blocked by compounds inhibiting the yeast-to-hypha transition. Furthermore, we found that OSIP108 is predominantly localized at the C. albicans cell surface. These data point to interference of OSIP108 with cell wall-related processes of C. albicans, resulting in impaired biofilm formation

Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach

Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM

Analysis of Glioblastoma Patients' Plasma Revealed the Presence of MicroRNAs with a Prognostic Impact on Survival and Those of Viral Origin

<div><p>Background</p><p>Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis in spite of a plethora of established diagnostic and prognostic biomarkers and treatment modalities. Therefore, the current goal is the detection of novel biomarkers, possibly detectable in the blood of GBM patients that may enable an early diagnosis and are potential therapeutic targets, leading to more efficient interventions.</p><p>Experimental Procedures</p><p>MicroRNA profiling of 734 human and human-associated viral miRNAs was performed on blood plasma samples from 16 healthy individuals and 16 patients with GBM, using the nCounter miRNA Expression Assay Kits.</p><p>Results</p><p>We identified 19 miRNAs with significantly different plasma levels in GBM patients, compared to the healthy individuals group with the difference limited by a factor of 2. Additionally, 11 viral miRNAs were found differentially expressed in plasma of GBM patients and 24 miRNA levels significantly correlated with the patients’ survival. Moreover, the overlap between the group of candidate miRNAs for diagnostic biomarkers and the group of miRNAs associated with survival, consisted of ten miRNAs, showing both diagnostic and prognostic potential. Among them, hsa miR 592 and hsa miR 514a 3p have not been previously described in GBM and represent novel candidates for selective biomarkers. The possible signalling, induced by the revealed miRNAs is discussed, including those of viral origin, and in particular those related to the impaired immune response in the progression of GBM.</p><p>Conclusion</p><p>The GBM burden is reflected in the alteration of the plasma miRNAs pattern, including viral miRNAs, representing the potential for future clinical application. Therefore proposed biomarker candidate miRNAs should be validated in a larger study of an independent cohort of patients.</p></div

Hierarchical clusters of rules for the validated targets of miRNAs detected in the plasma samples of GPs.

<p>Hierarchical clustering of the top 100 statistically significant rules (p≤0.05) is presented. The SegMine rules were derived from genes, representing validated targets of the GBM-related plasma miRNAs. Euclidian distance and Ward’s linkage criteria were used to compute the hierarchy.</p

Genes most frequently targeted by miRNAs, correlated to the presence of GBM or patient survival.

<p>The presented genes are validated targets of miRNAs differentially expressed in the plasma samples of GPs and the members of the HIo subgroup and/or correlated to patient survival according to the results of analyses of this study, obtained by using the miRTarBase [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125791#pone.0125791.ref032" target="_blank">32</a>]. <i>VEGFA</i>—vascular endothelial growth factor A, <i>HSPA1B</i>—heat shock 70kDa protein 1B, <i>ACTB</i>—actin beta, <i>HSP90AA1</i>—heat shock protein 90kDa alpha (cytosolic), class A member 1, <i>IGF1R</i>—insulin-like growth factor 1 receptor, <i>CCND1</i>—cyclin D1, <i>PTEN</i>—phosphatase and tensin homolog, <i>BCL2</i>—B-cell CLL/lymphoma 2, <i>CCNE1</i>—cyclin E1, <i>CDK4</i>—cyclin-dependent kinase 4, <i>PPIA</i>—peptidylprolyl isomerase A (cyclophilin A), <i>TUBA1B</i>—tubulin, alpha 1b, <i>WEE1</i>—WEE1 G2 checkpoint kinase, <i>CCND2</i>—cyclin D2, <i>CDK2</i>—cyclin-dependent kinase 2, <i>CDK6</i>—cyclin-dependent kinase 6, <i>BIRC5</i>—baculoviral IAP repeat containing 5, <i>EP300</i>—E1A binding protein p300, <i>RRM2</i>—ribonucleotide reductase M2.</p

The comparison of intra- and inter-individual miRNA expression variability in the plasma samples of 16 HIs.

<p>Variabilities are represented as boxplots showing miRNA expression coefficients of variation (CVs) for each individual and a complete dataset.</p