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Öğe Acute-onset axonal neuropathy following infection in children with biallelic RCC1 variants: a case series(Elsevier Science Inc, 2025) Harkness, J. Robert; Mcdermott, John H.; Marsden, Shea; Jamieson, Peter; Metcalfe, Kay A.; Khan, Naz; Macken, William L.Background The reasons why some individuals have severe neuropathy following an infection are not known. Through the agnostic screening of children with acute axonal neuropathy after an infection, we identified several families with biallelic variants in RCC1. We aimed to describe the clinical phenotype of these patients, and the molecular and cellular pathology associated with the genetic variants identified in these families. Methods For this case series, we identified children affected by a severe, acute-onset axonal neuropathy following infection through an international research consortium of paediatric neurologists and clinical geneticists from nine countries (Canada, Cyprus, Czechia, Germany, Iran, Saudi Arabia, Slovakia, T & uuml;rkiye, and the UK). Clinical assessments included nerve conduction studies and neuroimaging. We did exome or genome sequencing in DNA samples from all patients. We characterised the proteins encoded by the genetic variants by use of thermal stability and enzymatic assays, using recombinantly expressed proteins. We assessed cellular protein transport under heat or oxidative stress by use of immunofluorescence in primary fibroblasts, obtained from patients. We generated a humanised Drosophila knock-in model to assess the effects of stress on the in vivo function of RCC1. Findings Between Nov 2, 2011, and July 10, 2024, we identified 24 individuals from 12 families who had severe, acute-onset axonal neuropathy following infection (13 female and 11 male patients, with a mean age at diagnosis of 1 year 10 months [SD 227]). Eight biallelic missense variants in RCC1 were identified in affected individuals with autosomal recessive inheritance. Patients had variable phenotypes, ranging from rapidly progressive fatal axonal neuropathy to mild motor neuropathy with impaired walking. Neurological presentation was often secondary to an infection, resulting in initial misdiagnoses of Guillain-Barr & eacute; syndrome in several patients. 15 children had disease recurrence. The disease was fatal in 15 patients. The RCC1 variants in these patients code for proteins that alter GDP-to-GTP exchange activity and have reduced thermal stability in vitro. In primary fibroblasts, heat shock or oxidative stress revealed defects in Ran nuclear localisation and impaired nucleocytoplasmic transport. A Drosophila model of the disease revealed a fatal intolerance to oxidative stress. Interpretation We describe an autosomal recessive, acute-onset paediatric axonal neuropathy, seemingly triggered by infection, that affects individuals with biallelic RCC1 variants. In these children, the disease can mimic Guillain-Barr & eacute; syndrome. The pathological mechanisms underlying this novel axonal neuropathy might overlap with those of amyotrophic lateral sclerosis. Cellular studies indicate that RCC1 variants affect nucleocytoplasmic transport, which is crucial for healthy axonal function. Future studies should be directed at pre-symptomatic treatment by exploring ways to maintain nucleocytoplasmic transport. Copyright (c) 2025 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Öğe Living Liver Donor Paired Exchange: Can Anaesthesia Management Challenge?(Galenos Publ House, 2025) Erdogan, Mehmet Ali; Ucar, Muharrem; Colak, Yusuf Ziya; Demiroz, Duygu; Ozdes, Oya Olcay[No abstract available]Öğe Fear of Death and Sleep Quality in the Aftermath of an Earthquake(Slack Inc, 2025) Aktura, Seher Cevik; Celik, Hanife; Saritas, Seyhan Citlik; Ozden, GurkanPURPOSE: To examine fear of death and disruption in sleep patterns in individuals who have experienced an earthquake. METHOD: A descriptive and relationship-oriented study was performed with 322 individuals who experienced the February 6, 2023, earthquake in Turkey. Data were collected between February 20 and May 15, 2023. A personal information form, the Pittsburgh Sleep Quality Index (PSQI), and Death Anxiety Scale (DAS) were used for data collection. RESULTS: Participants'mean DAS score was 7.96 (SD = 1.05), and mean PSQI score was 8.74 (SD = 4.06). Statistically significant relationships were found between sex, marital status, and mean DAS score, and these variables accounted for 11.7% of the total variance. Similarly, statistically significant relationships were found among economic status, relationship to person trapped under the rubble, financial loss from the earthquake, and mean PSQI score, accounting for 11.3% of the total variance. Women and married people had greater fear of death, and those with good economic status, whose family members were buried under rubble, and who experienced financial loss as a result of the earthquake had lower sleep quality. CONCLUSION:The earthquake led to moderate fear of death and poor sleep quality among participants. Findings highlight the need for targeted support for vulnerable groups following disasters. [Journal ofPsychosocial Nursing and Mental Health Services, 63(2), 45-54.]Öğe Can nailfold capillaroscopy findings be a marker for uveitis in Behcet's syndrome?(Clinical & Exper Rheumatology, 2025) Zontul, S.; Inanc, E.; Can, A.; Tay, S. T.; Colak, H.; Cumurcu, T.; Yolbas, S.Objective To evaluate the differences between BS patients with uveitis and BS patients without uveitis and healthy controls in terms of nailfold capillaroscopic examination. Methods The study was performed on patients with a definite diagnosis of BS according to the International Criteria for Beh & ccedil;et's Disease, and healthy controls without BS. The participants were divided into three groups: BS patients with uveitis, BS patients without uveitis and healthy controls. All volunteers were examined by nailfold capillaroscopy for microvascular changes. Results A sample size of 90 participants, including 32 patients with BS with uveitis, 29 patients with BS without uveitis and 29 healthy controls, were included in our study. Fourteen (15.6%) BS patients with uveitis, 14 (15.6%) BS patients without uveitis and 16 (17.8%) healthy controls were female. In our study, we found microhaemorrhage occurrence to be significantly higher in BS patients with uveitis compared to the healthy control group (p=0.028). Although there was no significant difference compared to the BS without uveitis group, microhaemorrhage was approximately 2.5 times more common in the BS with uveitis group. The crossing medians were determined as 2.0 (0.8-3.3) in the BS with uveitis group, 1.3 (0.6-2.7) in the BS without uveitis group and 1.2 (0-3.2) in the healthy control group, showing a statistically significant difference across groups (p<0.001). In the post hoc crossing analysis, a significant difference was detected in the BS with uveitis group compared to the other two groups. A giant capillary was detected in one of the patients with uveitis, but no giant capillary was detected in the volunteers in the other groups. Conclusion Our findings show that microhemorrhage and crossing are associated with uveitis in BS patients.Öğe Dosimetric analysis of SIB whole brain radiotherapy planning: Comparison of coplanar VMAT and tomotherapy techniques(Wiley, 2025) Pepele, Eda Kaya; Temelli, OztunBackground Radiotherapy techniques have advanced significantly over the past few decades. Whole-brain radiotherapy combined with a simultaneous integrated boost (WBRT+SIB) is increasingly used to treat limited brain metastases. Purpose To retrospectively compare helical tomotherapy and coplanar volumetric modulated arc therapy (VMAT) for WBRT with a SIB-WBRT in patients with multiple brain metastases. Additionally, it emphasizes the importance of selecting appropriate evaluation indices when comparing SIB plans. Materials and methods Fifteen patients with 2- 3 metastatic lesions were retrospectively analyzed in this study. Treatment planning was performed using TomoHD and eclipse planning systems for tomotherapy and VMAT, respectively. Dose-volume histograms were used to assess the doses delivered to the target volumes and organs at risk (OARs). Quantitative metrics, including the homogeneity index (HI), conformity index (CI), and plan quality index (PQI), were used for the evaluation. Results Tomotherapy yielded significantly higher D98% values for both the planning target volume (PTV) WB and PTV_met compared with VMAT (p < 0.05). It also provided lower D-max and D-mean values for the lenses and eyes (p < 0.001 and p < 0.02, respectively). Tomotherapy was superior in terms of PTV whole-brain CI and PTV_met HI and CI (p < 0.05). However, no significant difference was observed in the PQI values between the techniques (p > 0.05). Conclusion Both tomotherapy and VMAT achieved acceptable target volumes and OAR doses in SIB applications. Tomotherapy showed advantages in terms of dose conformity and critical organ sparing. Moreover, this study highlights the impact of selecting appropriate evaluation indices on interpreting plan quality, particularly for complex treatment approaches such as SIB.Öğe Induced Pluripotent Stem Cell-Derived Parathyroid Organoids Resemble Parathyroid Morphology and Function(Wiley, 2024) Senkal-Turhan, Selinay; Bulut-Okumus, Ezgi; Aydin, Muhterem; Turkmen, Nese Basak; Taslidere, Asli; Sahin, Fikrettin; Yilmaz, SahinThe primary role of the parathyroid glands is to maintain calcium homeostasis through the secretion of parathyroid hormone (PTH). The limited proliferative capacity and differentiation of parathyroid cells hinder the generation of cell therapy options. In this study, parathyroid organoids are successfully generated from human-induced pluripotent stem cells (hiPSCs). At the end of the 20 days of differentiation, the parathyroid organoids exhibited distinct parathyroid morphology. Stereomicroscope, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis demonstrated the 3D arrangement of the cell layers in which intracellular structures of parathyroid cells resemble human parathyroid cellular morphology. Comprehensive molecular analyses, including RNA sequencing (RNA-Seq) and liquid chromatography/mass spectrometry (LC-MS/MS), confirmed the expression of key parathyroid-related markers. Protein expression of CasR, CxCr4, Gcm2, and PTH are observed in parathyroid organoids. Parathyroid organoids secrete PTH, demonstrate active intercellular calcium signaling, and induce osteogenic differentiation via their secretome. The tissue integration potential of parathyroid organoids is determined by transplantation into parathyroidectomized rats. The organoid transplanted animals showed significant elevations in PTH-related markers (CasR, CxCr4, Foxn1, Gcm2, and PTH). PTH secretion is detected in organoid-transplanted animals. The findings represent a significant advancement in parathyroid organoid culture and may offer a cellular therapy for treating PTH-related diseases, including hypoparathyroidism. iPSC-derived parathyroid organoids express PTH-related markers at the protein and gene levels. The transplantation of parathyroid organoids into parathyroidectomized rats shows their functional activity and tissue integration capability. iPSC-derived parathyroid organoids successfully release PTH both in vitro and in vivo. Parathyroid organoid technology may improve defective parathyroid function and related diseases. imageÖğe Health Effects of Plant-Based Diets in University Life: A Comprehensive Study on the Constipation, Sleep and Obesity(Iranian Scientific Society Medical Entomology, 2025) Toguc, HakanBackground: Plant-based diets have gained popularity due to their nutrient density and potential to reduce chronic disease risk. The aim of the study was to examine the relationship between diet quality and plant-based diets consumed with constipation, sleep duration and obesity in university students. Methods: In this study conducted between September and October 2024, 676 students were recruited as participants and data on socio-demographic information, daily sleep duration, presence of constipation, 24-hour food consumption record and food consumption frequency were collected. Diet Quality Index (DQI) and Plant-Based Diet Index (PBDI) were calculated from food consumption record and frequency data. Results: Constipation was present in 14.5% of the participants and the BMI of the participants was 21.84 +/- 3.47 kg/m(2). There was a significant relationship between age and constipation (P=0.013) and a weak negative relationship between age and sleep duration and PBDI (r=-0.103, P=0.007; r=-0.077, P=0.045, respectively); A weak negative correlation was found between BMI and PBDI and DQI (r=-0.092, P=0.016; r=0.173, P=0.000, respectively); a significant correlation was found between the presence of constipation and gender and income level (P=0.047; P=0.013, respectively). Conclusion: PBDI and DQI were associated with lower BMI and emphasised the potential of alternative nutritional models in the fight against obesity. The lack of an association between PBDI, DQI and sleep duration and constipation suggests that further research is needed. This study emphasises the importance of healthy eating and lifestyle interventions, but its design limits causal conclusions and requires further research.Öğe Effect of Earthquake-Related Trauma on Pubertal Maturation: Evidence From Skeletal Age Assessment Following the 2023 Kahramanmaras Earthquakes(Wiley, 2025) Kavasoglu, Nursezen; Bor, Sabahattin; Zortuk, Fundagul Bilgic; Hamamci, NihalThe devastating earthquakes centered in Kahramanmaras on February 6, 2023, caused significant psychosocial stress among children, which may have influenced the timing of pubertal onset. Since early puberty is associated with adverse physical and psychological outcomes, understanding the potential of environmental factors-such as natural disasters-to accelerate pubertal development is of great importance. In this retrospective study, a total of 1044 wrist radiographs taken from children aged 10-19 at four university dental faculties were evaluated. The radiographs were obtained during two time periods: pre-earthquake (February 6, 2022-February 6, 2023; n = 544) and postearthquake (February 6, 2023-February 6, 2024; n = 500). All images were assessed by a single expert using the skeletal maturation scale proposed by Grave and Brown. The MP3cap stage, which represents the peak of pubertal growth, was used as the main parameter. Due to the distribution of the data, nonparametric statistical tests were applied. In both female and male children, the age at the MP3cap stage after the earthquake was significantly lower compared to pre-earthquake values, indicating earlier pubertal growth spurts (p < 0.05). The findings indicate that the psychosocial stress induced by the Kahramanmara & scedil; earthquakes may have accelerated pubertal development in children. These results underscore the importance of closely monitoring the growth and development of children affected by natural disasters and providing them with comprehensive psychosocial and medical support.Öğe ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease(Wiley, 2025) Perez-Corredor, Paula; Arevalo-Alquichire, Said; Mazzarino, Randall; O'Hare, Michael; Muriel-Torres, Andres; Vacano, Guido; Vanderleest, TimothyINTRODUCTION: We described a protected case with familial Alzheimer's disease, homozygous for apolipoprotein E3 (APOE3) Christchurch variant (ApoE3Ch), exhibiting low tau protein levels despite genetic predisposition to the disease due to presenilin (PSEN)1-E280A. We reported the loss of interaction between ApoE3Ch and heparan sulfate proteoglycans (HSPGs) as a critical protective pathway. Here, we characterized differential interacting partners for both wild-type and Christchurch variants to identify additional protective mechanisms of ApoE3Ch. METHODS: We performed pull-down of mouse brain lysates using His-tag-ApoE3 recombinant proteins and determined interacting partners of ApoE3 via mass-spectrometry. We then performed in vitro and in vivo assays to validate the top interactors. RESULTS: We found enhanced binding of ApoE3Ch to tau and Dickkopf-1 (Dkk1, a WNT/beta-catenin antagonist) that resulted in reduced tau aggregation in vitro. We demonstrated that ApoE3Ch interacts directly with Dkk1 and tau, reducing tau pathology. These findings supported the hypothesis of novel protective effects of direct ApoE3Ch interactions.Öğe Full-Scale Regulation Enabled High-Performance Sodium O3-Type Layered Cathodes(Wiley-V C H Verlag Gmbh, 2025) Hong, Ningyun; Zhang, Shuncheng; Li, Jianwei; Wang, Haoji; Huang, Jiangnan; Hu, Xinyu; Zhang, BaichaoO3-type cathodes hold considerable promise in achieving rapid commercialization due to high energy density. However, severe structural/interfacial deterioration, along with kinetic hindrance, typically resulting in rapid capacity fading and serious safety risk at elevated cut-off voltages. Herein, inspired from solubility limitation of hetero-elements, synchronous surface-to-bulk multifunctionally full-scale modified O3-NaNi1/3Fe1/3Mn1/3O2 is proposed to maintain its state of health (SOH). The perovskite-type CaZrO3 protective layer in situ formed on the surface of primary particles, helps to construct a stable cathode-electrolyte-interphase architecture, mitigate the unexpected interfacial side reactions and prevent transition metal dissolution. Simultaneously, Ca2+ pillars, robust Zr-O bonds and the highly electronegative F- are adequately anchored into ternary lattice sites of Na-TM-O, respectively, thereby reinforcing the TMO6 octahedra and facilitating Na+ diffusion. Notably, the intrinsic lattice strain is effectively alleviated due to an additional intergrowth phase transition of P3-OP2. More impressively, migration of Jahn-Teller distorted Fe4+O6 is further restrained, originating from the strengthened coordination environment under deep-desodiation state. Consequently, as-designed NFM-CZF achieves an impressive rate capability and a remarkable capacity retention of 83.8 % after 300 cycles at 2 C. This elaborate work shed valuable insight into mechanism of regulating internal full Wyckoff-site and external surface structure for sodium-ion batteries with enhanced durability.Öğe New benzimidazole-indole-amide derivatives as potent α-glucosidase and acetylcholinesterase inhibitors(Wiley-V C H Verlag Gmbh, 2024) Naimi, Narges; Karimian, Somaye; Dastyafteh, Navid; Noori, Mild; Mohammadi-Khanaposhtani, Maryam; Dadgar, Armin; Larijani, BagherNew derivatives 6a-m with benzimidazole-indole-amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on alpha-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the alpha-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose. Moreover, the anti-AChE activity of these compounds, with the exception of one compound, was better than that of tacrine (standard inhibitor). The most potent compound against alpha-glucosidase was 3-methylphenyl derivative 6i and the most potent compound against AChE was 3,4-dimethoxyphenethyl derivative 6m. All the synthesized compounds were placed in the active sites of alpha-glucosidase and AChE by in silico docking method and the obtained binding energies were approximately in agreement with the in vitro observed data. Interaction modes of the most potent compounds 6i and 6m demonstrated that these compounds interacted with important residues of their target enzymes. Molecular dynamics simulation was conducted specifically on compound 6i in complex with alpha-glucosidase to obtain deeper insights into the behavior of this molecule. Furthermore, in silico pharmacokinetic and toxicity studies on the most potent compound predicted that these compounds have good profiles in terms of oral absorption and toxicity.Öğe 1-Alkyl-1H-Benzimidazolium Sulfonates as Non-Competitive Inhibitors of Polyphenol Oxidase(Wiley, 2026) Ergun, Adem; Cikrikci, Kubra; Gencer, Nahit; Arslan, Oktay; Uslu, Harun; Goktas, Bunyamin; Karatas, Mert OlgunPolyphenol oxidase (PPO) has been the subject of many inhibition studies due to its presence in many species, causing enzymatic browning in fruits and vegetables, and its pigmentation role in mammalian species. In the present study, the inhibitory properties of twelve 1-alkyl-1H-benzimidazolium sulfonates and two 1-alkyl-1H-benzimidazolium iodides on PPO activity have been investigated. The PPO enzyme was purified from banana using Sepharose 4B-tyrosine-p-aminobenzoic acid affinity gel chromatography. The effects of 14 different synthesized benzimidazole derivatives on the PPO enzyme were investigated, and they were found to significantly inhibit the enzyme in question. When ADME predictions were examined, it was seen that all compounds that include methylbenzenesulfonate structure showed good pharmacokinetic properties; only compounds 3a and 3b, which contain iodide, violated the Ghose rules. These compounds, which were effective at low concentrations, may serve as promising lead molecules for the development of PPO inhibitors with potential applications in food preservation, cosmetic formulations, and pharmaceutical research, pending further in vivo and formulation-based studies.Öğe Evaluating Polyphenol Derivatives on Cancer Stem Cells Using Two- and Three-dimensional Tumoroid Models: Insights From In Vitro and In Silico Studies(Wiley-V C H Verlag Gmbh, 2025) Bilgin, Sema; Tayhan, Secil Erden; Yasar, Seyma; Kocaman, Asli Yildirim; Koc, EsraCancer stem cells (CSCs) drive tumor initiation, metastasis, drug resistance, and recurrence, making them critical therapeutic targets. This study investigated two isoeugenol-derived polyphenolic compounds, designated as 1 and 2, in breast, prostate, and colon CSCs using monolayer and three-dimensional tumoroid models. After 48 h, both compounds significantly inhibited proliferation. In prostate cancer cells, compound 2 exhibited a lower half-maximal inhibitory concentration (17.18 mu M) than compound 1 (21.04 mu M) and 5-fluorouracil (5-Fu) (21.51 mu M). In three-dimensional tumoroids, compound 2 reduced tumoroid diameters by an additional 8% compared to 5-Fu. Molecular docking with AutoDock 4.2 revealed strong interactions between both compounds and key stemness regulators Sox2, Oct4, and Nanog. Compound 2 displayed the most favorable binding energies (-6.31 kcal/mol for Oct4, -5.36 for Nanog, and -4.62 for Sox2), suggesting stable complex formation that may disrupt core transcription factors. These findings support further investigation of polyphenol derivatives as potential CSC-targeting agents, with additional in vivo and pharmacokinetic studies needed to confirm therapeutic viability.Öğe Development of Potent Type V MAPK Inhibitors: Design, Synthesis, and Biological Evaluation of Benzothiazole Derivatives Targeting p38α MAPK in Breast Cancer Cells(Wiley-V C H Verlag Gmbh, 2025) Zoatier, Bayan; Yildiztekin, K. Gizem; Alagoz, M. Abdullah; Hepokur, Ceylan; Burmaoglu, Serdar; Algul, OztekinType V MAPK inhibitors are distinguished by their capacity to target both the ATP binding site and a specific allosteric site on the enzyme. The present work utilized in silico analysis with Maestro 13.8.135 (Schrodinger) software in conjunction with experimental investigations to enhance the antiproliferative efficacy and forecast the likely mechanism of action of benzothiazole derivatives. Approximately 28 compounds were developed, produced, and assessed for their antiproliferative properties against two breast cancer cell lines: ER+ (MCF7) and ER- (MDA-MB-231), in addition to one normal mouse fibroblast cell line (L929). Their antiproliferative activities were evaluated via the MTT test, with doxorubicin and cisplatin serving as reference drugs for comparison. Consequently, the compounds with the greatest activity against the MCF7 cell line were chosen, and their inhibitory effects on the p38 alpha MAPK enzyme were examined. The molecular docking studies of compounds 15 and 19 demonstrated significant binding affinities for p38 alpha MAPK. Molecular dynamics simulations conducted over 100 ns revealed that compounds 15 and 19 exhibit stability inside both the ATP-binding domain and the lipid domain of p38 alpha MAPK. The research focused on creating effective Type V MAPK inhibitors demonstrate that compounds 15 and 19 possess considerable ability to inhibit p38 alpha MAPK, hence establishing them as promising anticancer agents.Öğe Effects of Positive Psychotherapy-Based Education on Pain, Psychological Resilience, and Mental Well-Being After Lumbar Canal Stenosis Surgery: A Randomized Controlled Trial(Wiley, 2025) Pasahan, Ramazan; Kavak Budak, Funda; Saritas, Serdar; Kavak, Mustafa; Erkan, Fatma Melike; Akar, SabirAim This study was conducted to investigate the effects of positive psychotherapy-based education on pain, psychological resilience, and mental well-being after lumbar canal stenosis surgery.Materials and Methods A randomized controlled experimental study was conducted with 66 participants (33 control, 33 experimental) at the Brain and Neurosurgery Department of Medical Center X between March 2025 and July 2025. The control group received no intervention, while the experimental group received 8 weeks of psychoeducation based on positive psychotherapy. Pretests were administered to the control and experimental groups in March 2025. The training of the experimental group was administered between April 2025 and May 2025. Data collection tools included the Descriptive Characteristics Form, Pain Scale, Brief Resilience Scale, and Mental Well-Being Scale. It was determined that the data showed normal distribution, and parametric tests were used in the analyses. Chi-square and Fisher's exact tests were used to compare the descriptive characteristics of the patients in the experimental and control groups. A t-test was applied to the dependent and independent groups to determine the effect of the training.Findings In the study, no statistically significant difference was found in the comparison of the pretest pain, psychological resilience, and mental well-being scales of the control and experimental groups (p = 0.259, p = 0.177, p = 0.428). In the study, a statistically significant difference was found in the comparison of the posttest pain, psychological resilience, and mental well-being scales of the control and experimental groups (p = 0.001). In the study, a statistically significant difference was found in the pretest-posttest pain, psychological resilience and mental well-being scale total score averages of the experimental group (p = 0.001).Conclusion and Recommendations Positive psychotherapy-based education was effective in reducing pain and increasing psychological resilience, and mental well-being in patients after lumbar spinal stenosis surgery. Based on these findings, positive psychotherapy-based education can be recommended as an adjunct to pharmacological treatment for not only physical but also psychological recovery.Öğe Unveiling the Chemical Constituents and Inhibitory Roles of Extracts from Pinus Pinea L. Nut and Nutshell: A Novel Source for Pharmaceutical Antimicrobials(Wiley-V C H Verlag Gmbh, 2024) Unver, Tuba; Gurhan, IsmetAntibiotic resistance in infectious diseases has been a serious problem for the last century, and scientists have focused on discovering new natural antimicrobial agents. Pinus pinea has been used as a natural pharmacotherapeutic agent with antimutagenic, anticarcinogenic, and high antioxidant properties. In this study, GC-MS and LC-HR/MS were employed to analyze Pinus pinea L. nut and nutshell extracts. DPPH radical scavenging assay was performed to analyze the antioxidant properties of the extracts, but no activity was determined. GC-MS analysis showed that linoleic, oleic, and palmitic acids were the three most dominant fatty acids in nut and nutshell extracts, with ratios between 6.75 % and 47.06 % (v/v). LC-HR/MS revealed that the nutshell methanol extract had a higher phenolic content than other extracts, with vanillic acid (1.4071 mg/g). Antimicrobial activity assays showed that the minimum inhibitory concentrations (MIC) of the extracts varied between 5.94 and 190 mg/mL, and the most significant inhibition was seen in the nutshell methanol extract (MICs: between 5.94 and 47.5 mg/mL). Consequently, the antimicrobial activity of the extracts can be attributed to the dense fatty acids they contain, and the nutshell methanol extract showed the most potent inhibition related to the abundance of phenolic compounds in the extract.Öğe Listening to a Three-Dimensional Virtual Reality Sound: Effects on Stress Response of Adults(Wiley, 2025) Yilmaz, Yucehan; Disli, Faruk; Yildiz, SedatIntroduction: Virtual reality (VR) technologies utilizing three-dimensional (3D) sound may offer sensually engaging imitations. Thus, they may lead to relaxation or may provide a way of escaping from disturbing life events. As they have the potential to manage stress, the current study aimed to investigate the effects of VR 3D sounds on the stress axes of the body, namely the autonomic nervous system (ANS) and hypothalamo-pituitary-adrenal (HPA). Methods: Participants (19 men and 27 women, mean age 25.8 +/- 10.4 years), wearing on-ear headphones, did not listen to anything (control) or listened to a mono or 3D sound imitating a real-life situation taking place in a virtual barbershop. The control phase was immediately followed by mono or 3D phases. Half of the participants in mono and 3D phases were crossed, with 45 min intervals, to control the effect of time and habituation. Reactivity of ANS and HPA was measured by heart rate variability (HRV) and salivary cortisol measurements, respectively. HRV was measured during each phase by a 5-min continuous electrocardiogram recording. Salivary samples were taken during control recording and 15-min after mono or 3D sound listening. HRV parameters consisted of both time- and frequency-domain parameters, including standard deviation of R-R interval (SDNN), total power (TP), and low frequency/high frequency (LF/HF), as a measure for sympathovagal activity. Results: Compared to the control phase, the 3D sound increased almost all HRV parameters (including SDNN, TP, LF/HF, etc., p < 0.05) but did not affect salivary cortisol levels (p > 0.05). Effects of mono sound were in between the control and 3D sound phases. Conclusion: It seems that a 3D sound imitating a real-life environment does not affect HPA but increases HRV and sympathovagal balance, suggesting that VR 3D sound is likely to reproduce an ANS response observed in real life.Öğe 5(6)-Benzoyl-Substituted Benzimidazoles and Their Benzimidazolium Salts: Design, Synthesis, Characterization, Crystal Structure, and Some Metabolic Enzymes Inhibition Properties(Wiley-V C H Verlag Gmbh, 2025) Aktas, Aydin; Ozden, Eda Mehtap; Celepci, Duygu Barut; Taskin-Tok, Tugba; Ekti, Funda Sultan; Gulcin, Ilhami; Aygun, MuhittinHerein, the synthesis of 1-alkyl-5(6)-benzoyl-substituted benzimidazoles and their 1,3-bisalkylbenzimidazolium halide salts are presented and evaluated for some metabolic enzyme inhibition. All compounds were characterized using various spectroscopic techniques. Single-crystal XRD analysis was performed to determine the molecular structure of two compounds. The newly synthesized compounds exhibited significant inhibitory effects against acetylcholinesterase (AChE) and human carbonic anhydrase isoforms I and II (hCA I and hCA II) enzymes. These compounds demonstrated promising inhibition profiles, with Ki values ranging from 12.4 +/- 5.4 to 109.4 +/- 49.9 nM for hCA I, 23.1 +/- 11.2 to 115.0 +/- 17.9 nM for hCA II, and 0.7 +/- 0.3 to 4.4 +/- 1.0 nM for AChE. In comparison, the reference compound acetazolamide showed Ki values of 30.5 +/- 6.7 nM and 37.4 +/- 7.8 nM against hCA I and hCA II isoenzymes, respectively. Additionally, tacrine, a known AChE inhibitor, exhibited a Ki value of 5.1 +/- 2.7 nM. The dual inhibition of CA and AChE represents a valuable pharmacological approach with a wide range of therapeutic applications. The explanation and evaluation of the enzyme inhibition data obtained in line with the interactions of the synthesized compounds with hCA I, hCA II, and AChE enzymes were carried out by molecular docking studies. In particular, we focused on the three compounds (4e, 4f, and 4j for hCA I; 3g, 4f, and 4k for hCA II; and 4e, 4f, 4j, and 4l for AChE) with the highest potential activity with each enzyme. The physicochemical, ADME, drug-likeness, medicinal chemistry, and toxicity properties of the potential ligands were then predicted so that their drug candidate suitability for further studies is revealed.Öğe Design, Synthesis of 3-(Aryl)-1-(2-p-tolylthiazol-4-yl)prop-2-en-1-ones as Alpha(α)-Amylase Inhibitors(Wiley-V C H Verlag Gmbh, 2024) Iqbal, Hafsa; Haroon, Muhammad; Akhtar, Tashfeen; Aktas, Aydinalpha-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access alpha-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-Vis., FT-IR, H-1-, C-13-NMR, and elemental analysis). The synthesized compounds were evaluated for their alpha-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4 c (IC50=3.8 mu M), 4 g (IC50=14.5 mu M), and 4 f (IC50=17.1 mu M) were found excellent alpha-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4 f and 4 h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic alpha-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed alpha-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.Öğe Anti-lipoxygenase Evaluation of Different Achillea sp. Extracts(Wiley-V C H Verlag Gmbh, 2025) Subasi, Bilgen; Gunbatan, Tugba; Gurbuez, Ilhan; Inal, Ebrar; Kartal, Murat; Sucu, Melike; Icen, Mehmet SinaIn this present work, in vitro lipoxygenase (LOX) inhibitory activities of methanol extracts and different fractions of six Achillea species [A. biebersteinii, A. millefolium, A. cappadocica, A. wilhelmsii, A. setacea, and A. nobilis subsp. neilreichii] were evaluated. A microplate-based spectrophotometric method was utilized for the LOX assay. The phenolic composition was analyzed using the liquid chromatography-high resolution mass spectrometer (LC-HRMS). As a result, the A. biebersteinii (Malatya locality) ethyl acetate fraction showed the highest lipoxygenase inhibitory activity (72.9% inhibition), followed by the A. cappadocica ethyl acetate fractions with 66.9% and 60.4% inhibition, respectively. The phytochemical LC-HRMS analyses revealed that the active constituents of the studied fractions were vanillic acid, hyperoside, p-coumaric acid, quercetin, and chrysoeriol. The findings showed the active bioassay-directed fractions, as well compounds to the best of our knowledge for the first time, suggesting further future biological, pharmacological, and toxicological evaluations both in vitro and in vivo.
