PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397

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  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Pangenome Analysis and Genome-Guided Probiotic Evaluation of Cyclic Dipeptides Producing Levilactobacillus Brevis DY55bre Strain From a Lactic Acid Fermented Shalgam to Assess Its Metabolic, Probiotic Potentials, and Cytotoxic Effects on Colorectal Cancer Cells
    (Springer, 2025-10-01) Yetiman, Ahmet E.; Horzum, Mehmet; Kanbur, Ertan; Cadir, Mehmet; Bahar, Dilek; Gurbuz, Serife; Akbulut, Mikail
    This study investigates the genetic, metabolic, and probiotic characteristics of Levilactobacillus brevis DY55bre, a strain isolated from the traditional Turkish fermented beverage, shalgam. Whole-genome sequencing revealed a circular genome of 2.485 Mb with a GC content of 45.72%, predicted 2791 genes, and multiple CRISPR-Cas systems. Pangenome analysis demonstrated an open structure, with 18.9% core genes and 103 strain-specific genes, highlighting its genetic diversity. The DY55bre exhibits heterofermentative carbohydrate metabolism due to the presence of the araBAD operon and the lack of 1-phosphofructokinase (pfK) and fructose-1,6-bisphosphate aldolase enzymes. Probiotic evaluation revealed firm survival under simulated gastrointestinal conditions, including resistance to acidic pH (as low as 3.0) and bile salts (up to 1%), along with significant adhesion to intestinal epithelial cell lines (HT29;59.3%, Caco-2;87%, and DLD-1;60.8%). The strain exhibited high auto-aggregation (84.55%) and cell surface hydrophobicity (56.69%), essential for gut colonization. Safety assessments confirmed its non-hemolytic nature and absence of horizontally acquired antibiotic resistance genes. Notably, GC-MS analysis identified bioactive cyclic dipeptides, Cyclo(D-Phe-L-Pro) and Cyclo(L-Leu-L-Pro), which demonstrated cytotoxic effects against colorectal cancer cell lines, with IC50 values of 7.71 mg/mL for HT29 and 3.19 mg/mL for DLD-1. The cell-free supernatant exhibited antimicrobial activity against pathogens, likely due to the synergistic effects of cyclic dipeptides, organic acids, and other metabolites. Antioxidant assays revealed significant ABTS+ (76.63%) and DPPH (34.25%) radical scavenging activities, while cholesterol assimilation tests showed a 27.29% reduction. These findings position the DY55bre as a promising candidate for functional foods, nutraceuticals, and therapeutic applications, warranting further in vivo validation.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Synthesis, Characterization, and Comprehensive in Vitro and in Silico Evaluation of the Anti-Inflammatory Potential of Novel 1,2,3-Triazole–Arylidenehydrazide/Thiazolidinone Hybrids
    (Wiley-VCH verlag GmbH, 2025-09) Pepe, Nihan Aktas; Cakir, Furkan; Atalay, Tugba; Acar, Busra; Turgut, Gurbet Celik; Sen, Alaattin; Senol, Halil
    Five novel 1,2,3-triazole/arylidenehydrazide/thiazolidinone hybrid compounds (7-11) were synthesized and characterized using NMR, HRMS, IR, and HPLC purity analysis. The cytotoxicity of these compounds was evaluated on fibroblasts and THP-1 cells, showing that all compounds were nontoxic at the tested concentrations. The wound healing assay revealed that compounds 7, 9, and 10 significantly enhanced wound closure, with a 7.74%-32.69% improvement in treated cells. Compounds 8 and 11 showed moderate effects. Anti-inflammatory activity was assessed through qRT-PCR, demonstrating that compound 10 led to the most significant reduction in proinflammatory cytokines TNF-alpha, IL-1 beta, and NF-kappa B1. In addition, the expression of Iba1 protein in THP-1 cells confirmed that compound 8 showed the strongest anti-inflammatory effect, surpassing that of aspirin. Compound 10 showed the highest inhibition of NF-kappa B signaling and iNOS activity. Molecular docking studies revealed that compounds 10 and 11 had strong binding affinities to TNF-alpha and iNOS, with compound 11 showing the most stable interactions. Molecular dynamics simulations supported these findings, indicating that compound 11 demonstrated more stable binding to both targets. Overall, the results suggest that compounds 10 and 11 are promising anti-inflammatory candidates with potential for further development in therapeutic applications for inflammatory diseases.