The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.

Candidemia ranks among the top causes of nosocomial bloodstream infections, significantly increasing hospital stays and costs. Rapid and effective empirical antifungal therapy is crucial. The Candida parapsilosis species complex, the second most common cause of candidemia, has shown rising fluconazole resistance globally and in our country. Additionally, echinocandins exhibit higher minimum inhibitory concentrations (MICs) for C. parapsilosis, complicating empirical treatment decisions. This retrospective study analyzed 173 C. parapsilosis candidemia cases over 22 years in a tertiary care hospital. We compared 88 fluconazole non-susceptible (minimum inhibitory concentration [MIC] = 4 µg/mL: susceptible dose dependent; MIC ≥ 8 µg/ml resistant) and 85 fluconazole susceptible cases, examining demographics, clinical characteristics, risk factors, and 28-day mortality. Independent risk factors for fluconazole non-susceptibilty included age ≥ 66 years (p = 0.016), central venous catheter use (p < 0.001), total parenteral nutrition (p = 0.003), and colostomy (p = 0.049). Fluconazole non-susceptible cases had lower microbiological cure rates and higher mortality. Mortality in this group was independently associated with microbiological cure failure (p < 0.001). This study highlights the importance of identifying risk factors to estimate the likelihood of resistant pathogens, initiating targeted antifungal therapy, and providing individualized management. Monitoring local resistance patterns is essential to guide empirical therapy. Further multicenter research is needed to validate findings and optimize treatment for fluconazole resistant candidemia. Clinical trial number: Not applicable.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved manage- ment of PDAC. This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour hetero- geneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integra- tion of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical appli- cations. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.

Objectives: The purpose of this study was to investigate the effect of Olea europaea L. leaf extract (OLE) on senescence and senescence-associated secretory phenotype (SASP) caused by temozolomide (TMZ) in glioblastoma (GB).Materials and Methods: A senescence beta-galactosidase assay and a colony formation assay were used to determine the effects of OLE, TMZ, and OLE + TMZ on the cellular senescence and aggressiveness of GB cell lines T98G and U87MG. mRNA expression levels of p53, a senescence factor, interleukin (IL)-6, matrix metalloproteinases (MMP)-9, and nuclear factor kappa B1 (NF-kappa B1) as SASP factors and Bcl-2 and Bax as senolytic markers were assessed using quantitative reverse transcription-real-time polymerase chain reaction. Cells were double-stained with acridine orange and propidium iodide to observe the cell morphology.Results: TMZ increased the senescence rate of GB cells (p<0.001). Besides, OLE + TMZ reduced the proportion of senescent cells (p<0.001) and their capability to form colonies compared to TMZ-only-treated cells. Additionally, OLE + TMZ co-treatment elevated the mRNA expression levels of MMP-9, IL-6, NF-kappa B1, p53, and the Bax/Bcl-2 ratio compared to TMZ-only treatment. Especially in U87MG cells, involvement of OLE in TMZ treatments increased more than six times in the Bax/Bcl-2 ratio compared to TMZ-only, which induced the apoptosis-like morphological features (p<0.0001).Conclusion: Collectively, our findings presented the inhibitory effect of OLE on TMZ-mediated SASP-factor production in GB and, accordingly, its potential contribution to elongate the time of recurrence.

To develop and validate a deep-learning detection model (Mask R-CNN) and a complementary radiomics-based machine-learning analysis for peri-implantitis det