https://hdl.handle.net/20.500.12809/239 2026-06-29T05:05:03Z 2026-06-29T05:05:03Z Baysal, Ömür Jimenez‑Quiro, Catherine Cevher‑Keskin, Birsen Tör, Mahmut https://hdl.handle.net/20.500.12809/11236 2026-06-26T11:37:59Z 2026-01-01T00:00:00Z

Bacillus velezensis EU07 suppresses Fusarium graminearum via transcriptomic reprogramming Baysal, Ömür; Jimenez‑Quiro, Catherine; Cevher‑Keskin, Birsen; Tör, Mahmut Fusarium graminearum poses a major threat to global cereal production, necessitating sustainable control measures. This study elucidates the antagonistic mechanism of the biocontrol agent Bacillus velezensis EU07 against F. graminearum through combined transcriptomic and morphological analyses. Exposure to EU07 compromised fungal cellular integrity, causing severe hyphal distortion. RNA-seq profiling revealed that EU07 triggers a profound transcriptomic collapse rather than a standard stress response. Over 35% of the altered fungal transcriptome caused critical suppression, targeting essential metabolic hubs, secretome effectors, and master transcription factors to inhibit growth and loss of pathogenicity. In a compensatory defensive shift, the pathogen massively reallocated its transcriptional resources. This defence was characterised by a similar to 30-fold enrichment of transmembrane amino acid transporters for putative toxin efflux and an 80-fold enrichment of glutathione S-transferases to mitigate severe oxidative stress. Furthermore, EU07 suppressed core vulnerability nodes, including proline dehydrogenase (PRODH) and apolipophorin, disrupting the pathogen's osmotic resilience and membrane integrity. Molecular docking analysis indicated that the Bacillus lipopeptide iturin A directly targets apolipophorin with high affinity (- 7.2 kcal/mol). Our findings indicated that B. velezensis EU07 overwhelms F. graminearum through simultaneous metabolic starvation and loss of virulence, revealing highly vulnerable fungal targets for next-generation RNAi-based biocontrol.

2026-01-01T00:00:00Z Yıldız, Ayşegül Ghafoor, Naeem Abdul https://hdl.handle.net/20.500.12809/11008 2023-10-05T11:29:41Z 2023-01-01T00:00:00Z

Targeting MDM2-p53 Axis through Drug Repurposing for Cancer Therapy: A Multidisciplinary Approach Yıldız, Ayşegül; Ghafoor, Naeem Abdul Cancer remains a major cause of morbidity and mortality worldwide, and while current therapies, such as chemotherapy, immunotherapy, and cell therapy, have been effective in many patients, the development of novel therapeutic options remains an urgent priority. Mouse double minute 2 (MDM2) is a key regulator of the tumor suppressor protein p53, which plays a critical role in regulating cellular growth, apoptosis, and DNA repair. Consequently, MDM2 has been the subject of extensive research aimed at developing novel cancer therapies. In this study, we employed a machine learning-based approach to establish a quantitative structure-activity relationship model capable of predicting the potential in vitro efficacy of small molecules as MDM2 inhibitors. Our model was used to screen 5883 FDA-approved drugs, resulting in the identification of promising hits that were subsequently evaluated using molecular docking and molecular dynamics simulations. Two antihistamine drugs, cetirizine (CZ) and rupatadine (RP), exhibited particularly favorable results in the initial in silico analyses. To further assess their potential use as the activators of the p53 pathway, we investigated the antiproliferative capability of the abovementioned drugs on human glioblastoma and neuroblastoma cell lines. Both the compounds exhibited significant antiproliferative effects on the abovementioned cell lines in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) of CZ was found to be 697.87 and 941.37 μM on U87 and SH-SY5Y cell lines, respectively, while the IC50 of RP was found to be 524.28 and 617.07 μM on the same cell lines, respectively. Further investigation by quantitative reverse transcriptase polymerase chain reaction analysis revealed that the CZ-treated cell lines upregulate the expression of the p53-regulated genes involved in cell cycle arrest, apoptosis, and DNA damage response compared to their respective vehicle controls. These findings suggest that CZ activates the p53 pathway by inhibiting MDM2. Our results provide compelling preclinical evidence supporting the potential use of CZ as a modulator of the MDM2-p53 axis and its plausible repurposing for cancer treatment.

2023-01-01T00:00:00Z Gökçe Topkaya, Cansu Aslan, Sema Göktürk, Tolga Kıncal, Sultan Hökelek, Tuncer Güp, Ramazan https://hdl.handle.net/20.500.12809/10998 2023-10-03T11:27:21Z 2023-01-01T00:00:00Z

A new 1,2,4-triazine-n-oxide compound: Synthesis, crystal structure, Hirshfeld surface analysis and supercapacitor applications Gökçe Topkaya, Cansu; Aslan, Sema; Göktürk, Tolga; Kıncal, Sultan; Hökelek, Tuncer; Güp, Ramazan In this paper, we report the one-step, metal catalyst-free synthesis of 6-(4-chlorophenyl)-3,3-dimethyl-4-(N-oxide)-1,2,3,4-tetrahydro-1,2,4-triazine using 2,4-dihydroxyacetophenone and p‑chloro isonitrosophenyl hydrazine and its full characterization including single crystal X-ray analysis. A simple and straightforward method for the synthesis is presented and the compound is obtained in a moderate yield and high purity. It's molecular and crystal structures were determined and found that It belongs to triclinic system P -1 space group with a = 5.9173 (2) Å, b = 13.3113 (4) Å, c = 14.3963 (4) Å, α = 97.583 (2) °, β = 93.207 (2) °, γ = 91.378 (2) °, Z = 4 and V = 1121.71 (6) Å3. In the crystal structure, the intermolecular N–H⋯O hydrogen bonds link the molecules into infinite chains along the a-axis direction. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (48.4 %), H⋯C/C⋯H (16.6 %), H⋯O/O⋯H (13.7 %) and H⋯CI/CI⋯H (11.0 %) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. The electrochemical characterizations and the supercapacitor performances of the compound were also investigated. Although, the pretreated porous carbonaceous materials or nanostructures provide superior surface enhancement properties in terms of the electrode modifications for a wide range of electrochemical applications, here we found a better performance for the proposed single crystal hydrazone as an electrode modifier.

2023-01-01T00:00:00Z Kaur, Simranjit Saini, Adesh K. Tuli, Hardeep Singh Garg, Nancy Joshi, Hemant Varol, Mehmet https://hdl.handle.net/20.500.12809/10969 2023-09-19T11:09:15Z 2023-01-01T00:00:00Z

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy Kaur, Simranjit; Saini, Adesh K.; Tuli, Hardeep Singh; Garg, Nancy; Joshi, Hemant; Varol, Mehmet Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

2023-01-01T00:00:00Z