Browsing by Author "Tuluce, Y."

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Exploring Natural Compounds Targeting Pd-L1 and Stat3: Toxicogenomic Analysis, Virtual Screening, Molecular Docking, Admet Evaluation, and Biological Activity Prediction
(Bentham Science Publ Ltd, 2025) Karakus, F.; Kuzu, B.; Kostekci, S.; Tuluce, Y.
BACKGROUND: One of the most important targets in cancer immunotherapy is programmed cell death ligand 1 (PD-L1). Monoclonal antibodies developed for this target have disadvantages due to their low bioavailability and some immune-related adverse effects. Additionally, small molecules targeting PD-L1 are still in the experimental stage. At this point, discovering non-toxic natural compounds that directly or indirectly target PD-L1 is essential. In this in silico study, a comprehensive literature search was conducted to identify publications reporting the master regulator of PD-L1, which was suggested as a Signal Transducer and Activator of Transcription 3 (STAT3). The relationship between STAT3 and PD-L1 was further investigated through bioinformatic analysis. METHODS: Subsequently, natural compounds targeting PD-L1 and STAT3 were screened, and compounds with suitable toxicity profiles were docked against both PD-L1 and STAT3. Following molecular docking, the selected molecules underwent DNA docking, ADMET profile analysis, and in silico assessment of biological activities. The relationship between PD-L1 and STAT3 was determined in 52 out of the 453 articles, and it was further demonstrated in genegene interactions. Following the virtual screening, 76 natural compounds were identified, and after pre-filtering based on physicochemical properties, drug-likeness, and ADMET profiles, 29 compounds remained. RESULTS: Subsequent docking revealed that two compounds, 6-Prenylapigenin, and Gelomulide J, persisted. ADMET and biological activity prediction results suggested that 6-Prenylapigenin is non-toxic and has the potential to inhibit PD-L1 and STAT3 in silico. The present study highlights that STAT3 serves as the master regulator of PD-L1, and it further suggests that 6- Prenylapigenin exhibits the potential to modulate PD-L1 and/or STAT3. CONCLUSION: This finding could pave the way for the development of small molecules designed to block the PD-1/PD-L1 interaction by silencing the PD-L1 and/or STAT3 genes or reducing protein levels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Increased Oxidative Stress in Patients With Familial Mediterranean Fever During Attack Period
(Makerere Univ, Coll Health Sciences,sch Med, 2011) Ediz, L.; Ozkol, H.; Tekeoglu, I; Tuluce, Y.; Gulcu, E.; Koyuncu, I
Objectives: We aimed to investigate the status of oxidant and antioxidants during attack period (AP) and attack free periods (AFP) in Familial Mediterranean fever (FMF) patients. Methods: Measured the levels of malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and antioxidant vitamins (A,C and E) as well as the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in serum and whole blood of FMF patients in FMF-AP and FMF-AFP. Results: Levels of MDA and PC were found significantly higher (p <0.05) both in serum and whole blood of FMF-AP group compared with other groups. The CAT and GSH-Px activities in FMF-AP group were found markedly lower (p <0.05) comparing to HC group. However, there were no statistically significant differences between the groups in terms of antioxidant vitamin levels. Conclusions: Our study demonstrated increased oxidative stress in patients with FMF during AP. Investigations are needed to establish the effect of antioxidant supplementation on FMF attack frequency and severity. We also suggest that these increased MDA and PC levels and decreased antioxidants may be used as supportive markers to differentiate AP from AFP. These conclusions need to be validated in further multicenter studies with high number of FMF patients.
The Influence of Shift Work on Cognitive Functions and Oxidative Stress
(Cambridge Univ Press, 2013) Ozdemir, P. G.; Selvi, Y.; Ozkol, H.; Aydin, A.; Tuluce, Y.; Boysan, M.; Besiroglu, L.
Is Gdf5 Gene Promoter Polymorphism+104t/C Associated With Osteoarthritis in the Eastern of Turkey Population
(C M B Assoc, 2017) Tuluce, Y.; Yildirim, I. H.; Ozkol, H.; EdiZ, L.; Delen, V.
Osteoarthritis (OA) is the most common form of arthritis. Genetic factors have been shown to play important roles in the etiology of OA. The gene growth differentiation factor 5 (GDF5) has been implicated in skeletal development and joint morphogenesis in human and mice. A functional single nucleotide polymorphism (SNP) +104T/C in the 5'-UTR of GDF5 (rs143383) was reported to be associated with osteoarthritis susceptibility in Han Chinese and Japanese populations. Our objective was to assess whether this SNP was also associated with OA in the Eastern Turkey population. A total of 172 cases including 95 patients with idiopathic OA and 77 control cases were recruited into the study. DNA samples were extracted from peripheral blood lymphocytes of all cases by using salting out method. The +104T/C polymorphism was genotyped by PCR-RFLP method. In terms of genotype comparison there wasn't any correlation between patient and control groups. Frequency of C allele was found to be higher in-patient group than control group and statistical analysis showed a poor correlation in allele frequencies of the +104T/C SNP of GDF5 gene between cases and controls (p< 0.05). Significant correlation between GDF5 and OA has been reported in Asian population, especially T alleles were found in higher frequencies and related to OA. Our study did not confirm this association and also in term of T allele. Interestingly, we found higher frequency of C allele in patient group than control group and our results are compatible with the study carried out in Greek population.
Oxidative Status and Its Relation With Insulin Resistance in Young Non-Obese Women With Polycystic Ovary Syndrome
(Springer, 2012) Kurdoglu, Z.; Ozkol, H.; Tuluce, Y.; Koyuncu, I.
Background: Oxidative stress may play a role in the pathophysiology of polycystic ovary syndrome (PCOS). Insulin resistance (IR) also can be found in young non-obese women with PCOS. Hyperglycemia may increase reactive oxygen species production and decrease antioxidant levels. Aim: To investigate oxidative status and its relation with IR in young non-obese patients with PCOS. Material/subjects and methods: Thirty-one patients with hyperinsulinemic (no.=13) and normoinsulinemic (no.=18) PCOS and 29 healthy controls were included in this study. Serum levels of glucose, insulin, gonadotropins, total testosterone, DHEAS, SHBG, 2-h plasma glucose on oral glucose tolerance test, malondialdehyde (MDA), protein carbonyl (PC), reduced glutathione (GSH), beta carotene, vitamin A, C, E and the enzyme activities of catalase and glutathione S-transferase (GST), IR [by homeostasis model assessment (HOMA)-IR], and beta cell function [by HOMA-B] were assessed. Results: Serum glucose, insulin, total testosterone, DHEAS. HOMA-IR levels, and LH/FSH ratios were higher in young non-obese women with PCOS. Serum MDA and PC levels were also higher but GSH, vitamin C and E levels, and GST enzyme activity were lower in these women than in healthy controls, independently of the status of IR (p<0.05). Conclusions: Oxidative stress characterized by increased oxidants and decreased antioxidant levels which are independent of IR may be involved in the pathogenesis of PCOS in young non-obese women. (J. Endocrinol. Invest. 35: 317-321, 2012) (C)2012, Editrice Kurtis
Silibinin and Ellagic Acid Increase the Expression of Insulin Receptor Substrate 1 Protein in Ultraviolet Irradiated Rat Skin
(Taylor & Francis Ltd, 2020) Gorgisen, G.; Ozkol, H.; Tuluce, Y.; Arslan, A.; Ecer, Y.; Keskin, S.; Ragbetli, M. C.
Daily exposure to ultraviolet (UV) light induces inflammation and tumorigenesis in the skin. Silibinin and ellagic acid are natural products that exhibit anti-inflammatory and anti-tumorigenic properties. Insulin receptor substrate protein 1 (IRS1) is important for skin homeostasis and physiology, but its activity following UV radiation remains unclear. We investigated the effects of ellagic acid and silibinin on IRS1 expression in ultraviolet A (UVA) and ultraviolet B (UVB) irradiated rat skin. Forty-two female Wistar rats were divided randomly into six groups of seven animals. The dorsal skin of rats was exposed to UVA + UVB, then treated with ellagic acid and silibinin by gavage. IRS1 expression in skin tissues was determined by western blot analysis. IRS1 expression increased significantly following treatment with ellagic acid and silibinin in UVA + UVB irradiated skin compared to the UVA + UVB only group. After UVA + UVB treatment, ellagic acid effected greater induction of IRS1 expression than silibinin. Our findings suggest that the photoprotective roles of ellagic acid and silibinin may be due to induction of IRS1 expression in UVA + UVB treated rat skin.