Celebi, Demet; Baser, Sumeyye; Mahmoudnezhad, Aydin; Ari, Betul; Celebi, Ozgur; Genc, Sidika; Nigde, Esmanur; Karabulut, Kubra; Taghizadehghalehjoughi, Ali

Pancreatic cancer (PC) is one of the most aggressive malignancies of the digestive system, characterized by late diagnosis, resistance to conventional therapies, and poor survival outcomes. Therefore, the development of novel, effective, and targeted therapeutic strategies is urgently needed. This study aimed to evaluate the anticancer potential of Acinetobacter baumannii-derived outer membrane vesicles (OMVs) conjugated with Vaccinium myrtillus extract, a low-toxicity natural compound, against pancreatic cancer cells. For this purpose, V. myrtillus was conjugated with A. baumannii-derived OMVs, and the antimicrobial activity of the conjugate was assessed using disk diffusion, minimum inhibitory concentration, time-kill kinetics, and biofilm inhibition assays. The anticancer effects were investigated by treating PANC-1 pancreatic cancer cells and healthy fibroblast cells with OMVs (50 µg/mL) and increasing concentrations of V. myrtillus (5–250 µg/mL). After 24 h, cell viability and cytotoxicity (MTT, LDH), oxidative stress parameters (TAS, TOS, SOD, GR), PI3K/AKT/PTEN signaling pathway components, apoptotic markers (Annexin V/PI, BAX, Bcl-2, Caspase-8), and inflammatory cytokines (IL-1β, IL-10) were analyzed. The OMV–V. myrtillus conjugate (50 µg/mL OMV +250 µg/mL V. myrtillus) significantly reduced cell viability by approximately 60% through disruption of intracellular redox balance. Elevated oxidative stress triggered apoptotic signaling, approximately increased 50% LDH release, and enhanced inflammatory responses. Especially 50 µg/mL OMV +250 µg/mL V. myrtillus treatment group compared to the control group, which approximately increased to 1-fold IL-1β rate. Furthermore, the 50 µg/mL OMV +250 µg/mL V. myrtillus treatment group showed approximately a 0.75-fold increase in PTEN and BAX gene expression, accompanied by a correlated decrease in AKT and BCL-2 gene expression, compared to the control group. These results suggest that OMV-mediated delivery of V. myrtillus represents a promising synergistic therapeutic approach for treatment-resistant pancreatic cancer.

Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Taghizadehghalehjoughi, Ali; Aydin, Elif; Genc, Sidika; Hacimuftuoglu, Ahmet

Candida albicans is an opportunistic pathogen that can cause invasive infections, especially under conditions of immunosuppression and dysbiosis. Its presence alongside Pseudomonas aeruginosa and Escherichia coli may lead to polymicrobial biofilm-related infections. Due to rising antimicrobial resistance, alternative therapies are being explored, including luteolin, a natural flavonoid with reported in vitro antimicrobial activity. This study evaluated the in vitro antimicrobial and antibiofilm effects of luteolin against C. albicans, E. coli, and P. aeruginosa, both individually and in combination. Methods involved determining minimum inhibitory concentrations, using scanning electron microscopy, fibroblast viability tests, ELISA-based cytokine measurements, and RT-qPCR analysis of key biofilm- and quorum-sensing-related genes (luxS, lasI, and ALS1). MIC values were 0.011 mg/mL for individual strains and 0.046 mg/mL for the polymicrobial mixture. Luteolin treatment reduced microbial adherence and improved fibroblast viability compared to infected controls. Infection increased IL-1β levels and decreased IL-10 levels, effects that luteolin partially reversed. RT-qPCR showed downregulation of selected biofilm-related genes at 2×MIC. These findings demonstrate luteolin’s measurable antimicrobial and anti-biofilm effects in vitro under controlled laboratory conditions, supporting further validation in preclinical models to assess translational potential.

Ucar, Mahmut; Celebi, Ozgur; Celebi, Demet; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Kiliclioglu, Metin; Dabanlioglu, Bulent; Shahbazova, Masma; Yilmaz, Ahmet

Campylobacter jejuni (CJ), a major cause of bacterial gastroenteritis, employs exosomes to disseminate virulence factors and disrupt host immune homeostasis. This study investigated the therapeutic potential of Arabic Gum (AZ) and Lactobacillus acidophilus (LA), individually and in combination, against CJ exosome-induced intestinal injury in rats, with emphasis on inflammasome-related signaling and microbiota modulation. Rats received AZ, LA, or both following CJ exosome exposure. Molecular analyses, histopathology, and microbiome sequencing were performed to elucidate mechanistic responses. CJ exosomes activated key virulence pathways and triggered pronounced inflammatory signaling characterized by alpha kinase 1 (ALPK1), Nuclear Factor Kappa B (NF-κB), and NOD-like Receptor Pyrin (NLRP) upregulation, accompanied by epithelial injury and dysbiosis. Treatment with AZ or LA alone attenuated inflammasome activation and partially restored immune and microbial balance. Notably, the combined treatment produced a synergistic effect, effectively suppressing ALPK1/NF-κB/NLRP signaling and reestablishing a more physiologic microbial community structure. These improvements were associated with reductions in pro-inflammatory cytokines and markers of tissue damage, as well as substantial recovery in intestinal, hepatic, and splenic architecture. Overall, AZ and LA significantly mitigated CJ exosome-mediated pathology, with the combined therapy demonstrating superior efficacy. The findings suggest that co-administration of AZ and LA may offer a promising dual-modal strategy to counteract CJ-induced inflammatory and microbial disturbances, potentially supporting future therapeutic approaches targeting exosome-mediated pathogenesis.