There is increasing interest in the antimicrobial properties of honey. In most honey types, antimicrobial activity is due to the generation of hydrogen peroxide (H2O2), but this can vary greatly among samples. Honey is a complex product and other components may modulate activity, which can be further affected by commercial processing procedures. In this study we examined honey derived from three native Australian floral sources that had previously been associated with H2O2-dependent activity. Antibacterial activity was seen in four red stringybark samples only, and ranged from 12 to 21.1% phenol equivalence against Staphylococcus aureus. Antifungal activity ranged from MIC values of 19–38.3% (w/v) against Candida albicans, and all samples were significantly more active than an osmotically equivalent sugar solution. All honey samples were provided unprocessed and following commercial processing. Processing was usually detrimental to antimicrobial activity, but occasionally the reverse was seen and activity increased. H2O2 levels varied from 0 to 1017 μM, and although samples with no H2O2 had little or no antimicrobial activity, some samples had relatively high H2O2 levels yet no antimicrobial activity. In samples where H2O2 was detected, the correlation with antibacterial activity was greater in the processed than in the unprocessed samples, suggesting other factors present in the honey influence this activity and are sensitive to heat treatment. Antifungal activity did not correlate with the level of H2O2 in honey samples, and overall it appeared that H2O2 alone was not sufficient to inhibit C. albicans. We conclude that floral source and H2O2 levels are not reliable predictors of the antimicrobial activity of honey, which currently can only be assessed by standardized antimicrobial testing. Heat processing should be reduced where possible, and honey destined for medicinal use should be retested post-processing to ensure that activity levels have not changed.
Candida albicans is an opportunistic fungal pathogen. In immunocompromised individuals, it can cause bloodstream infections with high mortality rates. The ability to switch between yeast and hyphal morphologies is a critical virulence factor of C. albicans. In response to diverse environmental cues, several signaling pathways are activated resulting in filamentous growth. Interestingly, cell cycle arrest can also trigger filamentous growth although the pathways involved are not well-understood. Here, we demonstrate that the cAMP-PKA pathway is involved in the filamentous growth caused by G1 arrest due to the depletion of the G1 cyclin Cln3 and S phase arrest due to hydroxyurea treatment. The downstream mechanisms involved in filamentation are different between the two cell cycle arrest phenomena. Cln3-depleted cells require HGC1 and UME6 for filamentous growth, but hydroxyurea-induced filamentation does not. Also, the hyphal repressor Nrg1 is not involved in the suppression of Cln3-depletion and hydroxyurea-induced filamentous growth. The findings highlight the complexity of the signaling networks that control filamentous growth in which different mechanisms downstream of the cAMP-PKA pathway are activated based on the nature of the inducing signals.
Drug resistance, an impenetrable barrier in the treatment of ovarian cancer (OC), is often associated with poor outcomes. Hence, it is urgent to discover new factors controlling drug resistance and survival. The association between neurocalcin delta (NCALD) and cancer drug resistance is poorly understood. Here, we reveal that NCALD messenger RNA expression, probably regulated by DNA methylation and microRNAs, was significantly downregulated in at least three independent microarrays covering 633 ovarian carcinomas and 16 normal controls, which includes the Cancer Genome Atlas (TCGA) ovarian cohort. In the sub‐groups of the TCGA cohort, NCALD was suppressed in 90 platinum‐resistant tissues vs in 197 sensitive tissues. It is consistent with the quantitative reverse transcription polymerase chain reaction results revealing gene downregulation in carboplatin‐resistant SKOV3 and HeyA8 OC cells as compared with that in controls. Low expression of NCALD predicted poor overall survival (OS) in sub‐groups of 1656 patients, progression‐free survival (PFS) in 1435 patients, and post‐progression survival (PPS) in 782 patients according to Kaplan‐Meier plotter covering 1815 OC patients. Comprehensive bioinformatic analyses strongly implicated NCALD in the regulation of drug resistance, probably via competing for endogenous RNA (ceRNA) interactions with CX3CL1 and tumor immune‐microenvironment. NCALD acted as a ceRNA for CX3CL1 in 21 different cancers includes OC according to Starbase. These two genes negatively correlated with tumor purity and positively correlated with infiltration levels of neutrophils and dendritic cells in OC. The combined low expression of NCALD and CX3CL1 showed better prognosis potential for OS, PFS, and PPS in the 1815 OC patients than any of the individually tested genes. In summary, NCALD acts as a ceRNA for CX3CL1, and its downregulation may affect drug resistance and prognosis in OC. Thus, NCALD could be a new therapeutic target for anticancer therapy and a new biomarker for survival prediction in OC.
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