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21 →- ArticleYayıncıda açık erişim2026Investigation of the Effect of Akkermansia muciniphila Muc T (ATCC BAA-835) on TLR4/NF-Kappa B/NLRP2 Signaling Pathway and Intestinal Microbiota in Diarrhea-Predominant Irritable Bowel Syndrome in Rats
Ucar, Mahmut; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Kılıclıoglu, Metin; Yıldırım, Serkan
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder associated with gut microbiota dysbiosis, intestinal barrier dysfunction, and low-grade inflammation. This study aimed to evaluate the effects of Akkermansia muciniphila Muc T (ATCC BAA-835) on gut microbiota composition, intestinal barrier integrity, and TLR4/NF-κB/NLRP2-mediated inflammatory signaling in a stress-induced rat model of IBS-D. IBS-D was induced in rats using combined chronic and acute stress paradigms. Animals received A. muciniphila supplementation during the experimental period. Serum inflammatory cytokines and tight junction–related proteins were quantified by ELISA. Protein expression levels of TLR4, NF-κB, and NLRP2 were assessed by Western blotting. Gut microbiota composition was analyzed using 16 S rRNA gene sequencing of fecal samples. Histopathological and immunofluorescence analyses were performed to assess tissue inflammation and cellular damage. IBS-D rats exhibited increased inflammatory cytokine levels, impaired tight junction protein expression, activation of the TLR4/NF-κB/NLRP2 pathway, and significant alterations in gut microbiota diversity. A. muciniphila supplementation significantly attenuated inflammatory responses, restored intestinal barrier–associated proteins, and suppressed inflammatory signaling. Microbiota analysis revealed partial correction of dysbiosis, including increased abundance of beneficial taxa such as Faecalibacterium prausnitzii. A. muciniphila alleviates IBS-D–associated intestinal inflammation and barrier dysfunction by modulating gut microbiota composition and inflammatory signaling pathways, supporting its potential as a microbiota-based therapeutic strategy for IBS-D.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Evaluation of the Efficacy of Acarbose on Ovarian Microbiota Profile, Ovary–Gut Axis, and SAP (1–10) Gene Expression in Rats Administered With Candida albicans Exosomes
Dabanlioglu, Bulent; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Guler, Mustafa Can; Tanyeli, Ayhan; Ari, Betul; Kalayci, Sıla Ektas; Fakirullahoglu, Mesud; Kiliclioglu, Metin
Candida albicans is a commensal fungus of the vaginal and reproductive tract microbiota, but its overgrowth contributes to mucosal infections and reproductive dysfunctions. The fungus secretes exosomes carrying virulence factors, including secreted aspartyl proteinase (SAP) genes, which are critical for tissue invasion and immune modulation. Acarbose, an α-glucosidase inhibitor, has been shown to suppress C. albicans biofilm formation and hyphal transition. This study is aimed at evaluating the effects of acarbose on the ovarian microbiota, gut–ovary axis, and SAP gene expression profile in a rat model following exposure to C. albicans exosomes. Rats were divided into two groups: the control group received intraperitoneal C. albicans exosomes (8 log10 CFU/mL), whereas the acarbose group received the same exosomes followed by oral acarbose (25 mg/kg/day). Exosomes were characterized by NTA and SEM. Ovarian tissue gene expression (SAP1–10) was analyzed by qRT-PCR. Inflammatory cytokines and tight junction proteins were assessed via ELISA, and microbiota composition was determined using 16S rRNA sequencing. Acarbose significantly reduced IL-8 and TNF-α levels while increasing IL-10, ZO-1, claudin-5, and occludin expression compared with Candida-infected controls (p < 0.05). Gut microbiota diversity and classification success were higher in the acarbose group, indicating microbial balance restoration. Acarbose mitigated C. albicans exosome-induced inflammation and barrier dysfunction while enhancing microbial diversity, suggesting its potential role in modulating the ovarian–gut axis and reducing fungal virulence through SAP gene suppression.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Evaluation of gossypetin’s effects on gut microbiota profile and TLR4, Myd88, NFKB, and NLRP3 signaling pathways in rats
Akkas, Onder; Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Kalayci, Sıla Ektas; Ari, Betül; Guler, Mustafa Can; Dabanlıoglu, Bulent; Celebi, Selahattin; Kılıclıoglu, Metin
Gut microbiota plays a crucial role in maintaining host homeostasis by regulating metabolic processes and immune responses. Disruptions in microbial composition are closely associated with inflammatory diseases and are often linked to the activation of key signaling pathways such as Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa TLR4/MyD88/NF-κB and NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Natural bioactive compounds, particularly flavonoids, have gained attention due to their potential to modulate both gut microbiota and inflammation-related pathways. In this context, the present study aimed to evaluate the effects of gossypetin on gut microbiota composition and its regulatory role on TLR4, MyD88, NF-κB, and NLRP3 signaling pathways in a rat model. Adult female Wistar albino rats were divided into control and gossypetin-treated groups (50 mg/kg, oral gavage/56 days dose). Gut microbiota was analyzed by 16S rRNA sequencing, and protein expression levels were assessed using Western blot. Histopathological, immunohistochemical, and immunofluorescence analyses were also in liver, intestinal, and spleen tissue performed. Gossypetin administration reduced microbial diversity and altered microbiota composition, with increases in Mediterraneibacter spp., Blautia spp., and Lactobacillus spp. Western blot results showed significant decreases in NLRP3 (p ≤ 0.01) and NF-κB (p ≤ 0.05) levels, while TLR4 and MyD88 remained unchanged. Histological analyses revealed mild tissue alterations and increased oxidative stress markers. These results suggest that gossypetin modulates microbiota composition and exerts selective anti-inflammatory effects, highlighting its potential in microbiota-associated inflammatory regulation.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026Alpha-pinene mitigates renal ischemia–reperfusion injury via anti-oxidant, anti-inflammatory, anti-apoptotic effects and favorable eNOS/iNOS shifts in rats
Sebin, Saime Ozbek; Gulakar, Basak; Tanyeli, Ayhan; Guler, Mustafa Can; Erbas, Elif; Baser, Sumeyye; Celebi, Demet
Acute kidney damage frequently results from renal ischemia–reperfusion (RI/R). Alpha-Pinene (AP), a plant-derived monoterpene, has antioxidant, anti-inflammatory, and anti-apoptotic properties. We investigated whether AP limits early kidney damage after experimental RI/R. Female Wistar rats (n = 7 per group) were assigned to Sham, RI/R, RI/R + AP 50 mg/kg, or RI/R + AP 100 mg/kg. After 45 min of clamping both renal pedicles, a 24-h reperfusion period ensued. AP (i.p. immediately before reperfusion) was administered immediately before reperfusion. ELISA for inflammatory cytokines (IL-1β, TNF-α, IL-10), oxidative stress markers (MDA, IMA, SOD), and nitric oxide synthase isoforms (iNOS, eNOS). Histopathology (hematoxylin/Mallory's trichrome staining) for structural kidney injury scoring. Immunohistochemistry for apoptosis/autophagy markers (Bcl-2, cleaved caspase-3, LC3B) and NF-κB p65. In kidney homogenates, RI/R increased IL-1β, TNF-α, MDA, IMA, and iNOS and reduced IL-10, SOD, and eNOS compared to Sham. AP counteracted these alterations in a manner proportional to the dose; the 100 mg/kg dose most consistently approached Sham values. Histology showed diffuse vascular congestion/hemorrhage, tubular degeneration, and widening of Bowman's space after RI/R—all ameliorated by AP, with milder lesions at 100 mg/kg. Immunohistochemistry demonstrated lower cleaved caspase-3, LC3B, and NF-κB p65 (trend) with AP, alongside higher Bcl-2, supporting anti-apoptotic and anti-autophagic effects. A single intraperitoneal dose of AP administered immediately before reperfusion mitigated early renal injury after RI/R by improving redox balance, dampening inflammatory signaling, shifting the eNOS/iNOS profile toward endothelial protection, and reducing structural damage. AP merits further study as a potential adjunct to limit I/R–related kidney injury, including longer follow-up with functional renal endpoints and expanded dosing/timing strategies.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Alternative therapy against CTX-M broad spectrum β-lactamase resistance gene in Klebsiella pneumoniae infection: bee venom and bee venom-derived nanovesicle fraction
Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Taghizadehghalehjoughi, Ali; Dabanlıoglu, Bulent; Guler, Mustafa Can; Aydın, Elif; Yıldırım, Serkan
Antibiotic resistance is one of the most important problems threatening global public health by complicating the treatment of infections worldwide. The increase in resistant microorganisms creates a serious economic and social burden on healthcare systems and increasingly limits treatment options. Conscious use of antibiotics, infection control measures and the development of alternative treatment strategies are vital to ensure sustainability in health. Klebsiella pneumoniae is the most common gram-negative bacterium among urinary tract infections. Treatment of infections has become difficult due to the resistance to beta-lactam antibiotics. Bee venom (BV) and nanovesicle fractions isolated from BV are bioactive compounds with antimicrobial and antibiofilm activity. The aim of this study was to determine the antimicrobial and antibiofilm effects of BVand bee venom-derived nanovesicle fractions against the nosocomial infection agent K. pneumoniae, and to evaluate CTX-M PCR band detection under the tested conditions. Minimum inhibitory concentration (MIC), antibiofilm activity, fractional inhibition concentrations (FIC), CTX-M PCR band detection, and viability rates in L929 cells were evaluated for both BVand the bee venom-derived nanovesicle fraction against K. pneumoniae. MIC value of nanovesicle fractions isolated from BVwas determined as 1.95 mg/L. In combination with piperacillin and tazobactam, a synergistic effect was detected with a value of 0.5. Antibiofilm activity was measured with the highest absorbance value of 0.163 and 0.094 for BV nanovesicle fractions. A detectable CTX-M PCR band was observed in the BVgroup at 0.5× MIC, whereas no detectable band was observed at both concentrations by day 4. In the bee venom-derived nanovesicle fraction group, no detectable CTX-M PCR band was observed at 2× MIC and 0.5× MIC under the tested conditions. In contrast, detectable CTX-M PCR bands were observed in the piperacillin-tazobactam group. It was reported that the combination groups decreased the viability rate in L929 cell lines. The bee venom-derived nanovesicle fraction showed antimicrobial, antibiofilm, and PCR-based detection findings under the tested conditions, supporting the need for further investigation in broader in vitro and in vivo models.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2026The Effect of Microbiota and Evaluation of Released Cytokines in Schizophrenia Patients
Celebi, Demet; Celebi, Ozgur; Baser, Sumeyye; Ozcan, Halil; Taghızadehghalehjoughı, Ali; Hacimuftuoglu, Ahmet
Bidirectional communication between the gut microbiota and the brain has been increasingly recognized, with growing evidence suggesting its relevance in schizophrenia. Altered microbiota composition may contribute to gastrointestinal barrier disruption, immune activation, and metabolic dysfunction. Given the multifactorial etiology of schizophrenia involving genetic, epigenetic, and environmental factors, microbiota-related mechanisms may represent an important pathway in disease development. This prospective, controlled study investigated gut microbiota composition and systemic inflammatory markers in schizophrenia patients. Blood and stool samples were obtained from 14 patients with schizophrenia and 6 matched healthy controls. Microbiota profiles were determined through 16 S rRNA gene sequencing, while serum levels of Claudin-1, Occludin, E-cadherin, Zonulin, IL-1β, IL-6, and TNF-α were analyzed using ELISA. Firmicutes and Bacteroidota were the predominant phyla in both groups. However, alpha diversity (Shannon index, p < 0.05) and beta diversity (Permanova, p < 0.01) analyses showed significant differences between patients and controls. ELISA results demonstrated significantly elevated levels of IL-1β, IL-6, TNF-α, Claudin-1, and E-cadherin (all p < 0.05) in patients, whereas Occludin was significantly decreased (p < 0.05) and Zonulin levels were unexpectedly lower compared to controls. Results indicate significant gut dysbiosis and heightened systemic inflammation in schizophrenia patients. This interplay between microbial composition, intestinal permeability, and inflammatory processes may contribute to the pathophysiology of the disorder. Further studies with larger cohorts, including antipsychotic-naïve first-episode patients, are warranted to clarify causality and evaluate microbiota-targeted interventions as potential therapeutic strategies.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Synergistic effects of luteolin and Lactobacillus rhamnosus on methicillin-resistant Staphylococcus aureus biofilm inhibition: in vitro and in silico molecular deployment studies
Baser, Sumeyye; Celebi, Demet; Celebi, Ozgur; Kara, Adem; Turkes, Cuneyt
Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of healthcare-associated infections due to its remarkable biofilm-forming ability and multidrug resistance, highlighting the urgent need for alternative antimicrobial strategies. The present study investigated the antibacterial, antibiofilm, antivirulence, and cytotoxic effects of luteolin alone and in combination with Lactobacillus rhamnosus bacterial suspension natant against MRSA. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), disk diffusion, and fractional inhibitory concentration (FIC) assays. Biofilm inhibition was quantified using the crystal violet method, while the expression levels of biofilm-associated genes (icaA, icaB, icaC, icaD, clfA, clfB, fnbA, and fnbB) were determined by quantitative real-time PCR. Molecular docking analysis was performed to investigate the interaction between luteolin and S. aureus Sortase A (SrtA), and the cytotoxic potential of the treatments was evaluated in human dermal fibroblast (HDF) cells using the WST-8 assay. Luteolin exhibited MIC and MBC values of 128 and 256 µg/mL, respectively, whereas L. rhamnosus bacterial suspension natant also demonstrated antibacterial activity against MRSA. Combination treatment significantly increased the inhibition zone diameter and produced a synergistic interaction with an FIC index of 0.50. Moreover, the combination inhibited biofilm formation by approximately 75%, markedly exceeding the inhibitory effects of either treatment alone. Gene expression analysis revealed dose-dependent modulation of several biofilm-associated genes, particularly suppression of fnbA, suggesting interference with bacterial adhesion mechanisms. Molecular docking demonstrated favorable binding of luteolin to the active site of Sortase A with a predicted binding energy of − 9.220 kcal/mol, supporting its potential antivirulence mechanism. No significant cytotoxicity was observed in HDF cells within the tested concentration range. Collectively, these results demonstrate that luteolin combined with L. rhamnosus bacterial suspension natant represents a promising natural therapeutic strategy for controlling MRSA infections by simultaneously targeting bacterial growth, biofilm formation, and virulence while maintaining acceptable biocompatibility.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Probiotic Supplementation as an Alternative to Antibiotics in Bovine Sperm Cryopreservation: Effects on Motility, Oxidative Stress and Apoptosis
Ömür, Ali Doğan; Çelebi, Demet; Akarsu, Serkan Ali; Apaydin Yildirim, Betül; Uçak, Gamze; Acisu, Tutku Can; Aydin, Mehmet Akif; Başer, Sümeyye; Çelebi, Özgür; Koca, Recep Hakkı
This study aimed to evaluate the effects of probiotic supplementation on bovine sperm cryopreservation by assessing post-thaw spermatological and biochemical parameters. Twenty-four ejaculations were collected from four Simmental bulls using the artificial vagina method. Ejaculates exhibiting over 70% motility were pooled to eliminate individual variations and allocated into five experimental groups: antibiotic-free control group, antibiotic group, LA, BL and LR groups, respectively. Three probiotic strains, Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA) and Bifidobacterium longum (BL), were incorporated into a Tris egg yolk-based semen extender at a concentration of 109 CFU/mL. Following dilution, samples were equilibrated and subsequently stored in liquid nitrogen. Post-thaw evaluations were conducted for sperm motility and kinematic parameters using CASA, hypo-osmotic swelling test, fluorescent staining for chromatin integrity, acrosomal integrity and mitochondrial membrane potential, as well as oxidative stress biomarkers. Additionally, apoptosis and metabolism related proteins were quantified by ELISA. The results exhibited that probiotic treated groups had significantly higher total and progressive motility as compared with controls (p < 0.001). In comparison with the control group, BL supplementation showed significantly reduced lipid peroxidation and increased antioxidant enzyme activities, along with lowered TGF-β and Caspase-3 levels, indicating attenuated oxidative stress and apoptotic signalling (p < 0.001). In contrast with the control group, LR supplementation resulted in elevated MDA and apoptosis-related markers, suggesting strain specific pro-oxidative effects (p < 0.001). There were no significant differences observed in STAR or ATP synthase levels across the treatments. Altogether, the results exhibited that strains of probiotics, particularly BL, have the potential to serve as an alternative to antibiotics in bovine semen cryopreservation. Nevertheless, strain-dependent responses and limitations, especially with respect to DNA integrity, require further investigation.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Redox-mediated activation of PI3K/PTEN pathways by A. baumannii OMV–V. myrtillus conjugate in pancreatic cancer cells
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.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2026Single and multiple investigation activity potential luteolin against Candida albicans, Escherichia coli and Pseudomonas aeruginosa
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.
RDL Kalıcı Kaydıİncele
Tam Kayıt
| Alan | Değer | Dil |
|---|---|---|
| dc.date.accessioned | 2026-10-20T15:26:13.441372612Z | |
| dc.date.available | 2026-10-20T15:26:13.441372612Z | |
| dc.identifier.uri | https://rdlopen.rawdatalibrary.net/r/ebyu/22902 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.title | Farmasötik Mikrobiyoloji Anabilim Dalı | tr |
| dc.title | Department of Pharmaceutical Microbiology | en |
| dspace.entity.type | OrgUnit | |
| organization.identifier.code | ecz-farmasotik-mikrobiyoloji | |
| organization.unitType | department | |
| rdl.unit.alias | microbiol |
