https://hdl.handle.net/20.500.12809/180 2026-07-05T02:31:58Z https://hdl.handle.net/20.500.12809/11237 Potential Late Effects of Early Pregnancy Night-Shift Exposure on Hofbauer Cells in Term Placentas: A Histological and Ultrastructural Study Çetinavcı, Dilan; Elbe, Hülya; Yiğittürk, Gürkan; Sencar, Leman; Pirinçci, Fatih; Aydın, Hüsnü; Doğan, Kübranur Background Night shift work is considered an important environmental stressor with the potential to disrupt circadian rhythm and adversely affect placental structure and function during pregnancy. Materials and methods In this study, microscopic placental changes in pregnant women working regular daytime schedules (Group 1, n = 45) were compared with those of pregnant women who worked night shifts before pregnancy and during the first 24 weeks of gestation (Group 2, n = 45). Term placental samples were evaluated using hematoxylin and eosin (H&E) staining, along with immunostaining for phospho-BMAL1, CLOCK, and melatonin 1 A. Additionally, double immunofluorescence staining for CD68/CD163 and transmission electron microscopy analyses were performed. Results While the overall villous architecture remained largely preserved in both groups, the night-shift work group exhibited a higher frequency of microscopic lesions, including villous edema, abnormal vascularization, and hemorrhage. The mean histopathological damage score (MHDS) was significantly higher in group 2 (4.93 +/- 1.92) than in group 1 (2.29 +/- 1.10) (p < 0.001). Immunohistochemical analysis revealed significantly decreased expression of phospho-BMAL1, CLOCK, and melatonin receptor 1 A (MTNR1A) in group 2 (all p < 0.001). Immunofluorescence analysis revealed an increased number of CD68(+), CD163(+), and CD68(+)CD163(+) double-positive cells in group 2 (p < 0.005). Ultrastructural evaluation showed irregular microvilli and thickening/irregularity of the trophoblastic basal lamina in night-shift placentas. Conclusion In conclusion, night-shift work is associated with increased histopathological damage in the placenta, reduced circadian marker expression, and altered placental immune cell dynamics. Overall, these results indicate that circadian disruption related to night-shift work affects placental structure, molecular clock regulation, and immune microenvironment. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.12809/11233 Indole Metabolites as Modulators of Human Cholinesterases: A Kinetic and Molecular Docking Study with Comparison to Alzheimer's Drugs Gök, Müslüm; Çiçek, Çiğdem; Sarı, Suat; Sönmez, Gamze; Bodur, Ebru Objective: Alzheimer's disease (AD) is characterised by the gradual decline of cognitive function and impaired cholinergic neurotransmission due to reduced brain acetylcholine levels. AChE and BChE regulate acetylcholine degradation and are important targets in AD. This research investigated the inhibitory effects of indole-3-propionic acid (IPA) and indole-3-butyric acid (IBA) on human cholinesterases, using enzyme kinetics and molecular docking. Methods: We assessed the inhibitory effects of purified human BChE and commercially sourced erythrocyte-derived AChE using a modified Ellman spectrophotometric assay in a 96-well microplate. Kinetic parameters (Km, Vmax, and Ki) were determined by nonlinear regression and the Michaelis-Menten model, with Lineweaver-Burk plots used to analyse inhibition patterns. IC50 values were calculated by nonlinear regression analysis. Molecular docking simulations were performed to predict the binding positions of the indole derivatives and the reference Alzheimer's drugs donepezil and tacrine analogue in the active sites of AChE and BChE. Results: According to docking simulations, both indole derivatives bind to the catalytic gorge of cholinesterases, but with lower predicted affinity than reference inhibitors. Enzyme inhibition assays showed that IBA exhibited weak inhibitory activity against both enzymes, with IC50 values of 15.61 mM for BChE and 54.28 mM for AChE. IPA exhibited stronger inhibition, particularly against BChE, with an IC50 of 2056 & micro;M. Kinetic analysis indicated that IPA displays mixed-type inhibition of BChE (Km = 170.1 & micro;M, Ki = 1774 & micro;M), while its inhibition of AChE is competitive (IC50 = 3773 & micro;M, Km = 268.5 & micro;M, Ki = 6727 & micro;M). Conclusion: These findings suggest that short-chain indole metabolites can interact with cholinesterases, but are not potent inhibitors. Compared to IBA, IPA showed higher activity and distinct inhibition profiles for BChE and AChE. The development of new indole-based cholinesterase inhibitors may prove to be potent modulators of cholinergic enzymes. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.12809/11049 Platelet-Rich Plasma in Vitrification; is it Helpful or Harmful? Çavuşoǧlu, Türker; Gökhan, Aylin; Tomruk, Canberk; Şirin, Cansın; Kılıç, Kubilay Doǧan; Yiǧittürk, Gürkan Human and animal studies on cryoprotectants and freezing solutions are still needed to establish a simple yet reliable protocol and increase the success of cryopreservation. The main aim of this study was to evaluate the short- and longterm effects of platelet-rich plasma, a well-known antioxidant substance due to its contents including bioactive molecules and growth factors, on whole ovarian tissue cryopreservation. Fresh tissues (control group, G1) were subjected to histological tissue processing without any treatment. Ovaries treated with plateletrich plasma (PRP)-supplemented vitrification solution were subjected to tissue processing without cryostorage group 2 (G2) or following six months of cryostorage group 3 (G3). Steps in G2 and G3 were also performed for group 4 (G4) and group 5 (G5), respectively, except that the vitrification solution was supplemented with fetal bovine serum. PRP was activated with calcium chloride (CaCl2) after double centrifugation. Ethylene glycol, dimethyl sulfoxide, and sucrose were used as cryoprotective agents in all groups. Histomorphological changes were evaluated with the semi-quantitative histochemical-scoring algorithm. Apoptotic and antiapoptotic effects and intercellular connections were evaluated with immunohistochemical staining of Bax, Bcl-2, Caspase-3 (C3), Connexin-43 (Cx-43), and TUNEL analysis. Cryopreservation with PRPsupplementation (G3) significantly increased tissue degeneration (p<0.05). There was an increase in the number of degenerated both primary and secondary follicles (p<0.05), and an increase in the immune expression of Bax, C3 and Cx-43 and TUNEL assay in G3 was observed compared to other groups 2023-01-01T00:00:00Z https://hdl.handle.net/20.500.12809/10976 Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine Aksu, Serkan; Şirin Cerrahoğlu, Tuba; Bayır Hasırcı, Buse Rahime; Ulukan, Çağrı; Soyata, Ahmet Zihni Objectives: Migraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. Materials and Methods: This study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. Results: Improvements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after sixmonth tDCS in the active group than in the sham group. Conclusions: Long-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. Significance: Long-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia. 2023-01-01T00:00:00Z