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ArticleAçık Erişim2026/r/ebyu/10820
Liraglutide Attenuates Multiorgan Oxidative, Astroglial, and Mitochondrial Stress Responses in Thioacetamide-Induced Hepatic Encephalopathy
Bilgin, Yasin; Sari, Fatih Mehmet; Cicek, Betul; Kurt, Engin; Ozkaraca, Mustafa; Gungor, Ali; Kurt, Nezahat; Bilgin, Asli Ozbek
Hepatic encephalopathy (HE) is a complex complication of liver failure involving oxidative stress, astroglial activation, mitochondrial dysfunction, and multiorgan disturbances along the gut–liver–brain axis. This study investigated the therapeutic effects of liraglutide (LIRA) in a thioacetamide (TAA)-induced rat model of HE. Thirty male Sprague–Dawley rats were assigned to control, TAA, and TAA+LIRA 100, 200, or 400 µg/kg groups. HE was induced with TAA (200 mg/kg, intraperitoneally) for three consecutive days, followed by subcutaneous LIRA treatment for 14 days. Serum biochemical parameters, tissue oxidative and inflammatory markers, histopathology, and Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity were evaluated. TAA caused marked hepatic and cerebral structural injury, increased serum and brain glutamine concentrations, disrupted redox homeostasis, elevated MPO activity, and increased cerebral GFAP and multiorgan VEGFA immunoreactivity. LIRA partially improved hepatic and cerebral histopathology, reduced glutamine disturbances, attenuated selected oxidative, nitrosative, and inflammatory alterations, and modulated Nrf2, MFN2, AKT1, mTOR, GFAP, and VEGFA immunoreactivity in a tissue- and dose-specific manner. The 200 µg/kg dose produced the most consistent overall improvement, whereas the 400 µg/kg dose was less favorable for several endpoints. LIRA may therefore alleviate multiorgan stress associated with experimental HE, although further studies are required to confirm functional and mechanistic relevance.
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ArticleAçık Erişim2026/r/ebyu/10819
Turkish cross-sectional survEy of glycemic and other Metabolic parameters in patients with type 2 Diabetes in 2023: Comparison with 2018 nationwide data (TEMD-2 study)
Sonmez, Alper; Haymana, Cem; Demirci, Ibrahim; Cetinarslan, Berrin; Gonen, Mustafa Sait; Akbas, Emin Murat; Yalin, Gulsah Yenidunya; Avcı, Ugur; Tasci, Ilker; Salman, Serpil
Aim Five years after the first “Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with type 2 Diabetes” (TEMD-1), attainment of glycemic, arterial blood pressure (ABP), and LDL-cholesterol (LDL-C) goals was re-investigated in patients with type 2 diabetes mellitus (T2DM), with an additional focus on therapeutic inertia. Methods This cross-sectional study consecutively enrolled patients from 70 tertiary endocrine centers across Türkiye (November 2022–January 2023). Metabolic targets were HbA1c <7% (<53 mmol/mol), home ABP <135/85 mmHg, and risk-stratified LDL-C <55, <70, or <100 mg/dL (<1.4, <1.8, or <2.6 mmol/L). Therapeutic inertia was defined as failure to intensify treatment at enrollment. Results Among the 4956 participants (mean age: 58.9 ± 10.0 years, women: 59.8%), HbA1c, ABP, LDL-C and triple metabolic control target attainment rates were 36.7%, 71.1%, 8.7%, and 2.8%, respectively. Glycemic control rate was found lower than the previous survey (40.0% vs. 36.7%, p < 0.001), while LDL-C control rate improved (7.0% vs. 8.7%, p = 0.002). Patients with established cardiovascular disease (CVD) showed worse outcomes, with triple metabolic control rate of 1.6%. The rate of severely uncontrolled diabetes (HbA1c >9%/75 mmol/mol) was 23.6%. Therapeutic inertia was observed by 33.5%, persisting uniformly across subgroups. Younger age, male sex, longer diabetes duration, lower socioeconomic status, and microvascular complications were independently associated with poor glycemic control. Conclusions Metabolic control remains suboptimal in Turkish T2DM patients, and one-third of patients with severe hyperglycemia showed therapeutic inertia. Systematic interventions and intensified strategies are urgently needed to improve diabetes outcomes and treatment inertia ( ClinicalTrials.gov number NCT06347445 ).
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ArticleAçık Erişim2026/r/ebyu/10808
Investigation of the Protective Effect of Centella asiatica Against Doxorubicin-Induced Testicular Damage in Rats
Bedir, Fevzi; Suleyman, Zeynep; Kocaturk, Huseyin; Altay, Mehmet Sefa; Keskin Cimen, Ferda; Altuner, Durdu; Babayeva, Mansura; Suleyman, Halis
Doxorubicin (DOX) is an antineoplastic agent commonly used in cancer therapy that is known for its testicular toxicity. DOX-induced testicular injury involves inflammation, reactive oxygen species, and oxidative stress. Centella asiatica exhibits anti-inflammatory and antioxidant properties. The present experimental study aimed to determine the potential protective efficacy of Centella asiatica in a rat model of doxorubicin-induced testicular toxicity. Rats were randomly assigned to four groups: healthy control (HC), CA, DOX, and CA + DOX (CADX). An oral dose of 200 mg/kg Centella asiatica was administered to the CA and CADX groups. The HC and DOX groups received saline. One hour later, DOX (7.5 mg/kg) was intraperitoneally injected into the DOX and CADX groups on days 1, 4, and 7. Centella asiatica markedly attenuated the DOX-induced increase in malondialdehyde, nitric oxide, and pro-inflammatory cytokine levels, while preventing the decrease in superoxide dismutase activity in testicular tissue (p < 0.001). Centella asiatica reduced the severity of DOX-induced morphological damage in testicular tissue (p < 0.05). Moreover, it partially restored reproductive hormone function. In conclusion, Centella asiatica demonstrates significant potential in mitigating DOX-induced oxidative damage, attenuating testicular injury and preserving the functional integrity of the male reproductive system.
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ArticleAçık Erişim2026/r/ebyu/10803
Probiotic Supplementation as an Alternative to Antibiotics in Bovine Sperm Cryopreservation: Effects on Motility, Oxidative Stress and Apoptosis
Ömür, Ali Doğan; Çelebi, Demet; Akarsu, Serkan Ali; Apaydin Yildirim, Betül; Uçak, Gamze; Acisu, Tutku Can; Aydin, Mehmet Akif; Başer, Sümeyye; Çelebi, Özgür; Koca, Recep Hakkı
This study aimed to evaluate the effects of probiotic supplementation on bovine sperm cryopreservation by assessing post-thaw spermatological and biochemical parameters. Twenty-four ejaculations were collected from four Simmental bulls using the artificial vagina method. Ejaculates exhibiting over 70% motility were pooled to eliminate individual variations and allocated into five experimental groups: antibiotic-free control group, antibiotic group, LA, BL and LR groups, respectively. Three probiotic strains, Lactobacillus rhamnosus (LR), Lactobacillus acidophilus (LA) and Bifidobacterium longum (BL), were incorporated into a Tris egg yolk-based semen extender at a concentration of 109 CFU/mL. Following dilution, samples were equilibrated and subsequently stored in liquid nitrogen. Post-thaw evaluations were conducted for sperm motility and kinematic parameters using CASA, hypo-osmotic swelling test, fluorescent staining for chromatin integrity, acrosomal integrity and mitochondrial membrane potential, as well as oxidative stress biomarkers. Additionally, apoptosis and metabolism related proteins were quantified by ELISA. The results exhibited that probiotic treated groups had significantly higher total and progressive motility as compared with controls (p < 0.001). In comparison with the control group, BL supplementation showed significantly reduced lipid peroxidation and increased antioxidant enzyme activities, along with lowered TGF-β and Caspase-3 levels, indicating attenuated oxidative stress and apoptotic signalling (p < 0.001). In contrast with the control group, LR supplementation resulted in elevated MDA and apoptosis-related markers, suggesting strain specific pro-oxidative effects (p < 0.001). There were no significant differences observed in STAR or ATP synthase levels across the treatments. Altogether, the results exhibited that strains of probiotics, particularly BL, have the potential to serve as an alternative to antibiotics in bovine semen cryopreservation. Nevertheless, strain-dependent responses and limitations, especially with respect to DNA integrity, require further investigation.
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ArticleAçık Erişim2026/r/ebyu/10800
Investigation of antiphytoviral effects of thymol, eugenol, and 1,8-cineol essential oils on cucumber mosaic virus in Turkey
Karakus, Sinem; Akdura, Nevin; Culal-Kılıc, Handan
The exploration of natural antiviral agents, such as essential oils, is a critical area of research, offering promising alternatives for sustainable plant disease management and contributing to global agricultural resilience. In this regard, the present study investigated the antiviral efficacy of thymol, eugenol, and 1,8-cineol essential oils (EOs) against cucumber mosaic virus (CMV) in vivo. It focused on assessing the capability of these EOs, particularly at a concentration of 500 ppm, in both prophylactic and therapeutic contexts for plant health, particularly when applied prior to or concurrently with viral infection. The evaluation involved measuring a range of parameters, including local lesions of CMV on cucumber plants, symptom index, leaf width, plant height, and virus accumulation. Our findings demonstrated that thymol was significantly effective in mitigating CMV infection. Both eugenol and 1,8-cineole oils also showed efficacy in reducing local lesions when applied to host plants alongside the infecting virus. Based on our results, the essential oils exhibited substantial protective and curative effects against CMV, with the preventative (pre-inoculation) application proving more effective. In conclusion, this study highlights the potent antiviral activity of thymol, eugenol, and 1,8-cineole EOs against CMV, presenting them as viable alternative strategies for combating viral diseases in plants. In addition, our findings not only advance our understanding of plant-virus interactions, but also pave the way for more eco-friendly and effective agricultural practices, crucial in the face of escalating plant disease challenges worldwide.
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ArticleYalnız künye2026/r/ebyu/10797
What Works Against Peer Bullying? A Meta-Analysis of School-Based Interventions in Türkiye
Haspolat, Namık Kemal; Ağırkan, Murat; Ciminli, Alaattin; Koç, Muharrem
Peer bullying remains a persistent global concern with far-reaching implications for students’ psychological, social, and academic development. While numerous interventions have been developed to address this issue, their effectiveness within culturally specific contexts warrants further investigation. This meta-analysis synthesizes 35 empirical studies conducted in Türkiye, encompassing 1,534 participants aged 4 to 17. Using a random-effects model, the findings indicate that intervention programs are associated with reductions in bullying (ES = 0.78) and victimization (ES = 0.74) and improvements in social skills (ES = 0.62) and well-being (ES = 0.83), although effects varied across studies and should be interpreted in light of between-study heterogeneity. Exploratory moderator analyses suggested that effects were associated with educational level and participant type for bullying, and with theoretical background for victimization; however, these subgroup patterns should be interpreted cautiously given the limited number of studies in some categories and the fact that moderators were examined in separate models. In exploratory univariable meta-regression analyses, session duration was associated with bullying effect sizes, whereas the number of sessions was not. These results underscore the importance of developing comprehensive, theoretically informed, and culturally responsive anti-bullying strategies, while also suggesting potential mechanisms and boundary conditions that may inform the adaptation of such interventions beyond the Turkish context.
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ArticleYalnız künye2026/r/ebyu/10791
Psychometrıc propertıes of the Turkısh versıon of the postpartum depressıon scale for Mothers of Preterm Babies
Köse, Semra; Ayran, Gülsün
Background This study was conducted to evaluate the validity and reliability of the Turkish version of the Postpartum Depression Scale for Mothers of Preterm Babies. Methods This methodological study was conducted with 204 mothers. Research data were collected using a Questionnaire and the Postpartum Depression Scale for Mothers of Preterm Babies. Content and construct validity analyses and reliability analyses were used for data evaluation. Results The scale demonstrated excellent content validity (S-CVI = 0.98). CFA confirmed the three-factor structure of the original scale with acceptable model fit (χ2/df = 2.11, RMSEA = 0.074, CFI = 0.95). Factor loadings ranged between 0.46 and 0.88. The internal consistency of the total scale was acceptable (Cronbach's α = 0.758). Conclusion The Turkish version of the MPB-PDS is a valid and reliable tool for assessing postpartum depression in mothers of preterm infants during the early postpartum period and can be used as a practical screening tool in neonatal follow-up settings.
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ArticleAçık Erişim2026/r/ebyu/10789
Isolation of Pseudomonas aeruginosa from food and determination of their antibiotic resistance
Yilmaz, Nazife; Urganci, Nida Nur; Yildirim, Zeliha
Despite the fact that Pseudomonas aeruginosa is a well-known opportunist pathogen, it remains an understudied microorganism in the context of food safety. Due to its high adaptation capability, rapid reproduction and minimal growth necessities, P. aeruginosa is a common bacterium in the food chain. The resistance of P. aeruginosa to various antibiotics in clinical isolates has been extensively investigated and in-depth characterized. Conversely, information on food-borne isolates of this genus and species is insufficient. In this study, a total of 208 colonies were isolated from 144 food samples collected from different provinces and subjected to morphological, physiological, and chemical analyses. Based on the results, total 22 isolates obtained from milk (12) and chicken (10) samples and exhibiting characteristics specific to P. aeruginosa were identified at the molecular level using the 16 S rRNA region. The antibiotic resistance profiles of the identified isolates were evaluated against azithromycin and erythromycin (macrolides), cefoperazone and ceftazidime (cephalosporin), meropenem and imipenem (carbapenem), as well as amikacin (aminoglycoside) among others. As a result of 16 S rRNA analysis, it was determined that only the 10 isolates obtained from raw milk samples were P. aeruginosa. The prevalence of antibiotic resistance among P. aeruginosa isolates was found to be variable. All isolates were observed to be susceptible to amikacin, imipenem, and piperacillin/tazobactam, while they were resistant to erythromycin, nalidixic acid, ampicillin, kanamycin, and chloramphenicol. Only the RM16 strain was susceptible to tetracycline, RM18 to meropenem, and RM20 and RM24 showed intermediate susceptibility to gentamicin.
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ArticleYalnız künye2026/r/ebyu/10788
In Vitro Cholinesterase Inhibition and Computational Investigation of some 1,2,3-triazole Derivatives as Dual AChE/BuChE Inhibitors
Tan, Ayse; Dilek, Esra
In vitro anticholinesterase activities of a series of 1,2,3-triazole derivatives, 9(a-e) and 10(f-l), were evaluated against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBuChE), using donepezil as a reference inhibitor. Enzyme inhibitory activities were characterized by IC50, inhibition constants (Ki), and inhibition mechanisms. All target compounds exhibited potent inhibitory activity against both enzymes. 9e demonstrated the highest activity against eeAChE (Ki = 7.69 ± 1.24 nM), outperforming donepezil (Ki = 25.28 ± 5.79 nM). 9b showed the strongest inhibition against eqBuChE (Ki = 3.36 ± 0.67 nM), whereas donepezil displayed comparatively weak activity (Ki = 43.48 ± 10.36 nM). To further elucidate ligand–enzyme interactions, molecular docking, molecular dynamics simulation (MDS), MM/GBSA, and structure–activity relationship studies were performed. Docking results indicated that all target compounds exhibited higher binding affinities for both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE than for BuChE. MDS and MM/GBSA analyses confirmed the stability of the selected complexes, without significant fluctuations over 50 ns, and showed that while 9e was selective for hAChE-CAS, 9b bound similarly to both hBuChE sites. Taken together, all target compounds, particularly 9e and 9b, may serve as novel dual AChE/BuChE inhibitor candidates.
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ArticleAçık Erişim2026/r/ebyu/10786
Structural analysis of ITS 1 gene of Leishmania tropica and evaluation of a novel ligand, benzo[d][1, 3]dioxol-5-yl 4-acetamidobenzenesulfonate, via molecular modeling methods
Yasar, Mehmet Murat; Yasar, Ekrem; Yorulmaz, Nuri; Gurses, Gulcan; Celik, Habip; Guney, Murat; Tas, Ahmet; Tanriverdi, Zubeyde; Yentur Doni, Nebiye
Introduction – Leishmaniasis, a prevalent tropical disease caused by intracellular protozoa of the genus Leishmania, poses significant health challenges globally, exacerbated by migration waves from endemic regions. Despite its widespread impact, an effective vaccine for leishmaniasis remains elusive. Historically, antimony compounds have been employed in its treatment, but the emergence of resistant strains necessitates the development of new therapeutic agents. Addressing this need, our study focused on the structural characterization of a previously uncharacterized protein from Leishmania tropica using computational biomolecular techniques. Methods – We identified and docked the ligand benzo[d][1, 3]dioxol-5-yl 4-acetamidobenzenesulfonate (3) and synthesized the reaction of sesamol (1) with sulfonyl chloride (2), and the NMR and IR spectra were used for characterization, a potential inhibitor of this protein, followed by a 300-ns simulation using the GROMACS software. Results – The results showed that the protein structure in the ITS1 gene region of L. tropica consisting of 875 amino acids was effectively inhibited. In addition, based on the broad pharmacological properties of sesamol and sulfonate esters, as well as the results obtained from ProTox-III analysis, compound 3 was synthesized and its effect on L. tropica was investigated. This evaluation was further supported by DataWarrior, SwissADME, and ADMETlab analyses. The ligand’s moderate binding affinity (ΔG = −6.29 kcal/mol), the formation of multiple hydrogen bonds (n = 4), its sustained binding throughout the 300-ns simulation, and the observed decrease in root mean square fluctuation (RMSF) values collectively support the idea that the synthesized compound may act as a potential inhibitor. Conclusion – However, experimental studies are required to conclusively confirm its inhibitory efficacy. This study provides valuable insights for the development of new therapeutic approaches against leishmaniasis.
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ArticleYalnız künye2026/r/ebyu/10782
Associations Between Nutritional Status, Sleep Quality, and Clinical Factors in Patients With Metastatic Prostate Cancer
Akagunduz, Digdem Dogan; Sahin, Hilal; Hendem, Engin; Akagunduz, Baran
PURPOSE – Malnutrition and poor sleep quality are common but underrecognized issues among patients with metastatic prostate cancer (mPC). This study aimed to examine the associations between nutritional status, sleep quality, and clinical outcomes in men with mPC. METHODS – In this cross-sectional study, 91 men with stage IV prostate cancer were evaluated for nutritional status using the Subjective Global Assessment (SGA) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Clinical and laboratory parameters, including albumin, hemoglobin, C-reactive protein (CRP), and quality-of-life scores (EORTC QLQ-C30 and QLQ-PR25), were compared across SGA categories and sleep quality groups. Multivariable logistic regression was used to identify predictors of poor sleep (PSQI >5).RESULTS – Overall, 60.4% of patients were castration-resistant, and 38.5% were severely malnourished (SGA C). Poor sleep quality was observed in 65.9% of patients and was significantly more prevalent among those with moderate-to-severe malnutrition (P < .001). Patients with worse nutritional status exhibited lower albumin and hemoglobin levels, higher CRP, poorer performance status, and worse quality-of-life scores across all domains (P < .001). In multivariable analysis, independent predictors of poor sleep included higher CRP (odds ratio [OR], 1.33 [95% CI, 1.11 to 1.61), lower hemoglobin (OR, 0.66 [95% CI, 0.46 to 0.93]), and poorer nutritional status (SGA C v A, OR, 5.06 [95% CI, 1.70 to 15.05]).CONCLUSION – Malnutrition and systemic inflammation are closely linked with impaired sleep quality and diminished quality of life in mPC. Nutritional screening and targeted interventions may represent an important component of supportive care for optimizing well-being in this population.
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ArticleAçık Erişim2026/r/ebyu/10781
Clinical Assessment of Medical Device–Related Pressure Injury Risk: Profiling Risk Levels in Patients Using Medical Devices
Aydin Kahraman, Handan; İpek Çoban, Gülay; Bozcu Kartal, Ebru
Objective: This study aimed to evaluate the risk of medical device-related pressure injury (MDRPI) development among patients exposed to medical devices and to assess the clinical utility of the Medical Device-Related Pressure Injury Risk Assessment Scale (MDRPIS). Methods: This clinical assessment study included 132 patients receiving care in intensive care, palliative care, and home-care units. The MDRPIS total score ranges from 8 to 27, with scores of 8–12 indicating high risk, 13–21 indicating moderate risk, and 22–27 indicating low risk. The scale was used to assess MDRPI risk associated with life-sustaining medical devices. Its psychometric performance was evaluated through analyses of internal consistency, criterion validity against the Braden Scale, and diagnostic accuracy using receiver operating characteristic (ROC) analysis. Results: The MDRPIS demonstrated strong discriminative ability for identifying patients at risk of MDRPI, with an area under the curve (AUC) of 0.822. A cut-off score of ≤16 was identified as the optimal threshold for detecting high-risk patients. Patients with MDRPIS scores of 16 or lower had a significantly higher incidence of MDRPI than those classified as low risk (p < 0.001). Respiratory support devices, particularly non-invasive ventilation (NIV)/continuous positive airway pressure (CPAP) masks and tracheostomy flanges or securement devices, were identified as the most significant risk factors for injury development. The highest incidence of MDRPI was observed among patients in intensive care units, followed by those in palliative care and home-care settings, indicating a statistically significant concentration of device-related risk in high-acuity care environments (p < 0.05). Conclusions: Clinical settings, particularly intensive care and palliative care units, should incorporate the MDRPIS into routine risk assessment protocols to facilitate targeted preventive interventions, including prophylactic dressings and advanced fixation techniques for patients using high-risk devices such as NIV masks and tracheostomy securement systems. The systematic implementation of the MDRPIS may support more effective allocation of nursing resources and enhance patient safety by enabling the early identification and prevention of avoidable device-related pressure injuries. Furthermore, the findings indicate that an MDRPIS score of 16 or below represents a clinically meaningful threshold for initiating preventive interventions.
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ArticleAçık Erişim2026/r/ebyu/10780
A new approach for lung cancer diagnosis: parallel feature learning
Tastimur, Canan
Lung cancer, one of the most common types of cancer worldwide, can be fatal. Early diagnosis saves lives. Computed tomography (CT) is used in the diagnosis of the disease. Since the radiology specialist evaluates this X-ray result, the specialist's interpretation can vary. Furthermore, the analysis by the radiologist is both time-consuming and costly. However, a cancer diagnosis approach based on deep learning models supports the radiologist's decision. In this study, a parallel feature learning architecture developed for lung CT images was designed. This architecture focuses on learning different features from each parallel path by using deformable and dilated convolution layers together. Dilated convolution captures semantic features in images with different dilated rates ratios by expanding receptive field, while deformable convolution better captures structural changes. This mechanism allows for more flexible and distinctive feature extraction without significantly increasing computational complexity. The proposed architecture was tested on three different lung cancer datasets: the Public Lung Cancer Dataset, IQ-OTH/NCCD, and LIDC-IDRI. Experimental findings demonstrate robust and consistent classification performance, achieving accuracy rates of 99.44%, 98.75%, and 98.62%, respectively. This shows that the proposed architecture offers a reliable solution for lung cancer diagnosis.
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ArticleAçık Erişim2026/r/ebyu/10779
Assessment of methylene blue and NAD on LPS-induced acute brain injury: effects on neuroinflammation, oxidative stress, and blood–brain barrier integrity in a rat endotoxemia model
Doganay, Songul; Üstündağ, Hilal; Erbaş, Elif; Yanar, Sevinc; Hayme, Serhat; Kurt, Nezahat
Sepsis-induced brain dysfunction remains a significant challenge with limited therapeutic options, warranting exploration of multi-target approaches. Methylene blue (MET) is a phenothiazine derivative with mitochondrial-enhancing and electron transport chain regulatory properties, while nicotinamide adenine dinucleotide (NAD) serves as a crucial cofactor in cellular energy metabolism and redox reactions. This study investigated the therapeutic effects of MET and NAD, individually and in combination, in lipopolysaccharide (LPS)-induced sepsis model. Male Sprague–Dawley rats (n = 35) were randomized into five groups: control, LPS (8 mg/kg), LPS + NAD (250 mg/kg), LPS + MET (15 mg/kg), and LPS + NAD + MET. Brain tissues were analyzed for oxidative stress, inflammation, and blood–brain barrier integrity. The combination therapy demonstrated the most pronounced improvements across clinical parameters, antioxidant capacity evidenced by significantly elevated superoxide dismutase levels (p < 0.001) and cerebral histopathological outcomes. It also significantly reduced myeloperoxidase activity (p < 0.001) compared to the LPS group. Pro-inflammatory cytokines IL-6 and IL-8 were significantly decreased in both MET and NAD monotherapy groups (p < 0.05), while TNF-α showed a decreasing trend without statistical significance. Brain-derived neurotrophic factor levels were maintained in the combination group, comparable to controls, while TGF-β showed differential modulation across treatment groups. Immunohistochemical analysis revealed LPS-induced blood–brain barrier disruption, evidenced by reduced occludin expression (p < 0.01), increased aquaporin-4 expression in perivascular astrocytic end-feet (p < 0.05), and elevated glial fibrillary acidic protein reactivity in protoplasmic astrocytes (p < 0.01). In conclusion, MET and NAD individually provided significant protection against LPS-induced brain injury by reducing neuroinflammation, oxidative stress, and neuronal damage. The combined treatment offered incremental benefits in certain outcomes. These findings suggest that both agents may have therapeutic potential in SAE.
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ArticleYalnız künye2026/r/ebyu/10777
Is “normal” ferritin truly enough? Strong correlation between iron stores and RLS severity in patients with normal ferritin levels
Tanoğlu, Ceyda; Ersoy, Alevtina
Objective We aimed to investigate the relationship between peripheral iron stores and symptom severity in drug-naive patients with idiopathic Restless Legs Syndrome (RLS) whose serum ferritin levels were within the laboratory reference range. Additionally, we sought to determine the independent effects of age, sex, comorbidities, and biochemical parameters in predicting RLS severity. Materials and methods This cross-sectional study was conducted at the neurology outpatient clinic of a single university hospital. A total of 113 drug-naive patients with idiopathic RLS were prospectively enrolled during clinical visits. Patients with ferritin levels outside the laboratory reference range (22–322 μg/L) or with major confounding comorbidities (e.g., peripheral neuropathy, renal failure, pregnancy) were excluded to ensure sample homogeneity Demographic data and comorbidities were recorded through face-to-face interviews. Disease severity was assessed by a neurologist using the International Restless Legs Syndrome Rating Scale. Ferritin, magnesium, vitamin B12, vitamin D, folate; and hemoglobin were analyzed in fasting venous blood samples. Multiple linear regression analysis was used to identify independent predictors of symptom severity. Results The mean age of the participants was 52 ± 13.8 years, and their median ferritin level was 51.4 μg/L. Multiple regression analysis identified serum ferritin level (p < 0.001) and age (p = 0.001) as independent and significant predictors of RLS severity. No independent effects of sex, hemoglobin, vitamin D, or other comorbidities on severity were detected. Conclusion Even when serum ferritin levels are within the so-called “normal” limits, a very strong negative correlation exists between ferritin level and symptom severity. Our findings highlight the importance of evaluating ferritin not merely as a threshold value in RLS management but as a continuous parameter that can be associated with symptom severity even within normal ranges.
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ArticleAçık Erişim2026/r/ebyu/10775
Protective Effects of Adenosine Triphosphate and Flunarizine on Erlotinib-Induced Ovarian Damage: An Experimental Study
Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Kuzucu, Mehmet; Yılmaz, Nesrin; Yazici, Gülcenaz; Hendem, Engin; Süleyman, Halis
(1) Background: Erlotinib is a tyrosine kinase inhibitor (TKI) widely used in cancer therapy; however, its potential adverse effects on ovarian tissue have not been fully elucidated. The present study aimed to investigate erlotinib-induced ovarian injury and to evaluate the protective effects of adenosine triphosphate (ATP) and flunarizine, administered alone or in combination, using biochemical and histopathological analyses in a rat model. (2) Methods: Thirty female rats were randomly allocated into five groups (n = 6 per group): healthy control, erlotinib, ATP + erlotinib, flunarizine + erlotinib, and ATP + flunarizine + erlotinib. ATP (5 mg/kg, intraperitoneal) and flunarizine (5 mg/kg, oral gavage) were administered daily for two weeks, while erlotinib (5 mg/kg) was given orally every two days for two weeks. Ovarian tissues were collected for oxidative stress analysis and histopathological evaluation, and blood samples were obtained for the measurement of serum prolactin and AMH levels. (3) Results: Erlotinib administration resulted in significant oxidative stress and histopathological alterations in ovarian tissue, accompanied by a reduction in serum AMH levels, while prolactin levels remained unchanged. Treatment with ATP or flunarizine partially attenuated these alterations. (4) Conclusions: Combined ATP and flunarizine administration showed stronger protective effects, improving biochemical parameters and preserving ovarian histology, suggesting a protective role against erlotinib-induced ovarian injury.
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ArticleAçık Erişim2026/r/ebyu/10773
Effects of ATP and Taxifolin on Atezolizumab-Induced Renal Injury: A Biochemical, Histopathological, and Immunofluorescence Evaluation
Kilic, Adil Furkan; Sezgin, Esra Tuba; Huseynova, Gulbaniz; Sarigul, Cengiz; Ozkaraca, Mustafa; Gungor, Ali; Mammadov, Renad; Suleyman, Halis; Cimen, Orhan
Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to investigate and comparatively evaluate the protective effects of adenosine triphosphate (ATP) and taxifolin against atezolizumab-induced renal tissue injury in rats. Methods: Animals were divided into four groups: healthy (HG), atezolizumab (ATZ), ATP + atezolizumab (ATAZ), and taxifolin + atezolizumab (TXAZ). ATP (4 mg/kg, i.p.) and taxifolin (50 mg/kg, oral) were administered for six days, while atezolizumab (10 mg/kg, i.p.) was given on days 1 and 4. On day 7, renal tissues were collected for biochemical, histopathological, and double immunofluorescence analyses. Results: Atezolizumab significantly increased malondialdehyde (MDA) levels and decreased total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels, indicating enhanced oxidative stress and impaired antioxidant defense. These changes were accompanied by tubular degeneration and increased expression of apoptotic markers. Both ATP and taxifolin significantly ameliorated these alterations; however, ATP demonstrated a more pronounced protective effect. Conclusions: In conclusion, ATP and taxifolin attenuated the biochemical, histopathological, and immunofluorescence alterations associated with atezolizumab administration. ATP exhibited a more pronounced protective effect than taxifolin under the conditions of this experimental model. Nevertheless, further experimental studies are required to elucidate the mechanisms underlying these effects.
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ArticleAçık Erişim2026/r/ebyu/10772
Simultaneous bioanalytical method development and validation of ibuprofen and phenyramidol HCl in human plasma using high–performance liquid chromatography with photodiode array detection and its application in a pharmacokinetic study
Kızıltas, Nurgul; Akman, Tugrul Cagri; Karabayir, Yasemin
The co-administration of ibuprofen (IBU) and phenyramidol HCl (PHE) is frequently preferred for the management of musculoskeletal disorders to enhance therapeutic efficacy. This study aimed to develop and validate a rapid, sensitive and cost-effective high–performance liquid chromatography–photodiode array (HPLC–PDA) method for the simultaneous determination of IBU and PHE in human plasma and pharmaceutical preparations, and to demonstrate its applicability in pharmacokinetic studies. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of phosphate buffer (pH 6.0 ± 0.05) and methanol (30:70, v/v) at a flow rate of 1.0 mL·min −1. The retention times of IBU and PHE were 3.7 and 2.7 min, respectively, with a total analysis time of 6 min. The method showed excellent linearity within the range of 0.05–40.0 μg·mL −1 for both drugs, with LLOQ values of 0.05 μg·mL−1 for IBU and 0.0025 μg·mL−1 for PHE. The plasma samples were collected at four time points (0.0, 1.0, 4.0 and 8.0 h) after oral administration of IBU and PHE. Cmax, Tmax and AUC0–8 were calculated, with Cmax of 16.14 μg·mL−1 for IBU and 3.71 μg·mL−1 for PHE, while Tmax was 1.0 h for both. Despite limitations in the number of sampling time points, the method proved highly applicable for determining pharmacokinetic profiles and for routine quality control analyses. Its short analysis time, high sensitivity and low sample volume requirement make it a powerful tool for clinical research and therapeutic monitoring. This is the first validated HPLC–PDA method applied to the simultaneous pharmacokinetic evaluation of IBU and PHE in human plasma.
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ArticleYalnız künye2026/r/ebyu/10771
Modification for the Repair of Nasal Septal Perforation: A Bipediculated Crescent-Shaped Septal Flap
Sahin, Abdulkadir; Sakat, Muhammed Sedat; Kilic, Korhan; Kars, Ayhan
Nasal septal perforation (NSP) is an anatomic defect located in the nasal septal cartilage/bone and mucosa. The most common cause of NSPs is septoplasty. Repair of NSPs is difficult regardless of the surgical technique due to their location and the health of the surrounding tissues. Currently, no technique has been defined to be used for the closure of all NSPs. We aimed to present our bipediculated crescent-shaped unilateral slide flap technique, which we designed and used as a modification for closure of NSPs, and its surgical results. A retrospective medical record review of patients who underwent NSP repair in our clinic was performed. All patients underwent a surgical procedure with the same technique by the same surgeon. Thirty-six patients were included in the study. The mean age of the patients was 35.58±9.6. The most common cause of NSP was previous septal surgeries. The NSP dimensions of the patients were between 5 and 23 mm. The NSP closure rate was determined as 94.4% in the 6-month follow-up results after surgery. A bipediculated crescent-shaped unilateral sliding flap is an effective, easy, and modification in the repair of NSPs.
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Review ArticleAçık Erişim2026/r/ebyu/10770
The P2X7 receptor/NLRP3 inflammasome signaling axis in sepsis: molecular mechanisms, organ-specific pathophysiology, and emerging therapeutic strategies
Üstündağ, Hilal
Sepsis remains a leading cause of mortality in intensive care units worldwide, representing life-threatening organ dysfunction arising from dysregulated host responses to infection. The purinergic P2X7 receptor (P2X7R) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome have emerged as critical regulators of inflammatory responses during sepsis pathogenesis. Extracellular adenosine triphosphate (ATP), released as a danger-associated molecular pattern from damaged and dying cells, activates the P2X7R, triggering potassium efflux that serves as the cardinal signal for NLRP3 inflammasome assembly. The activated inflammasome complex mediates caspase-1-dependent proteolytic maturation of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18, while simultaneously inducing gasdermin D (GSDMD)-mediated pyroptotic cell death—an inflammatory form of programmed cell death characterized by membrane pore formation, cellular swelling, and release of intracellular contents. Paradoxically, emerging evidence indicates that excessive P2X7R activation during sepsis progression induces profound mitochondrial dysfunction in circulating monocytes, leading to impaired NLRP3 inflammasome function and a state of immunoparalysis that coincides with an increased mortality. This comprehensive review examines the molecular mechanisms governing P2X7/NLRP3 signaling in sepsis; critically evaluates its dual and seemingly contradictory roles in hyperinflammation versus immunosuppression; delineates organ-specific manifestations across the lung, kidney, heart, brain, liver, and intestine; and systematically evaluates emerging therapeutic strategies including direct NLRP3 inhibitors such as MCC950, selective P2X7R antagonists, IL-1 receptor blockade, GSDMD inhibitors, and natural compounds with inflammasome-modulating properties. Understanding the temporal dynamics of this signaling axis is crucial for developing precision-targeted interventions that appropriately balance pathogen clearance with prevention of excessive inflammatory tissue damage.
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