Celebi, Ozgur; Baser, Sumeyye; Ari, Betul; Celebi, Demet; Dabanlioglu, Bulent; Genc, Sidika; Taghizadehghalehjoughi, Ali

Bacterial outer membrane vesicles (OMVs) are emerging as natural nanocarriers for cancer therapy due to their ability to deliver bioactive molecules and to penetrate the tumor microenvironment. This study investigated the combined effects of Escherichia coli-derived OMVs and Myristica fragrans extract on pancreatic ductal adenocarcinoma (PDAC) cells. OMVs (50 µg/mL) and M. fragrans extract (IC₅₀: 25 µg/mL) significantly reduced PANC-1 cell viability and increased LDH release after 24 h of treatment (p < 0.01). The combination treatment induced oxidative stress, evidenced by increased total oxidant status and decreased antioxidant capacity. Molecular analysis showed upregulation of PTEN expression, reduced phosphorylated AKT levels, and an increased IL-1β/IL-10 ratio. These changes elevated the Bax/Bcl-2 ratio and activated caspase-3, indicating induction of apoptosis (p < 0.01). Our findings suggest that OMVs can effectively deliver M. fragrans phytochemicals to cancer cells, modulating oxidative balance and triggering apoptosis through the PTEN/AKT signaling pathway. This study provides preclinical evidence that combinations of microbial vesicles and plant extracts may enhance therapeutic efficacy against PDAC.

Celebi, Selahattin; Celebi, Ozgur; Celebi, Demet; Baser, Sumeyye; Dabanlioglu, Bulent; Ektas Kalayci, Sila; Aslan, Sumeyye; Islamoglu, Fatma; Taghizadehghalehjoughi, Ali

Pseudomonas aeruginosa is a clinically important opportunistic pathogen characterized by high antibiotic resistance and strong biofilm-forming capacity, posing a major therapeutic challenge, particularly in immunocompromised patients. In this study, we aimed to evaluate the antibiotic resistance profiles and biofilm-forming abilities of clinical isolates, and to investigate the antibiofilm potential of the probiotic strain Lacticaseibacillus rhamnosus. A total of 66 clinical isolates were analyzed, revealing high levels of antibiotic resistance, while 87.9% of isolates demonstrated biofilm-forming capacity. Treatment with L. rhamnosus at 25% and 50% concentrations resulted in significant antimicrobial and antibiofilm effects. MIC and antibiofilm assays indicated that these effects were dose- and cell density-dependent. Scanning electron microscopy analyses confirmed the structural disruption of biofilms following treatment. Furthermore, real-time PCR results demonstrated that the expression levels of key biofilm-associated genes (algD, pelF, pslD, ppgl, and PAPI-1) were reduced by more than 50%. Importantly, this study provides evidence that L. rhamnosus can effectively inhibit both biofilm formation and biofilm-associated gene expression in multidrug-resistant P. aeruginosa isolates, highlighting its potential as a promising alternative or adjunctive biocontrol strategy against biofilm-related infections. These findings contribute to the growing body of research on probiotic-based approaches targeting antimicrobial resistance and biofilm-associated pathogenicity.

Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Ari, Betul; Dabanlioglu, Bulent; Genc, Sıdıka; Taghizadehghalehjoughi, Ali

Pancreatic cancer, characterized by its aggressive progression and limited therapeutic options, remains a malignancy with high mortality rates. This study evaluates the potential of bacterial extracellular vesicles (EVs) as immunotherapeutic carriers, focusing on Neisseria elongata-derived exosomes conjugated with a methanol extract of Cassia fistula, a plant with known anticancer properties. The cytotoxic and apoptotic effects of this complex were systematically analyzed using the PANC-1 pancreatic cancer cell line. MTT and LDH assays revealed a concentration-dependent reduction in cell viability and enhanced cytotoxicity. Mechanistic analyses demonstrated upregulation of pro-apoptotic BAX/BCL-2 ratio and modulation of PTEN/AKT signaling pathways, indicating activation of intrinsic apoptosis. Furthermore, increased levels of the pro-inflammatory cytokine IL-1β and suppression of anti-inflammatory IL-10 suggested immunomodulatory effects. Elevated reactive oxygen species (ROS) levels corroborated the induction of oxidative stress-mediated apoptosis. These results underscore the dual functionality of Neisseria elongata exosomes as both drug carriers and biological response modifiers. The biocompatibility and targeting efficiency of bacterial EVs position them as a novel therapeutic platform for gastrointestinal cancers. This study provides the first preclinical evidence supporting the use of non-pathogenic bacterial exosomes in oncology, highlighting their translational potential for improving treatment outcomes in pancreatic cancer.