Polat, Seher; Simsek, Yasin

Background: Polyendocrine Metabolic Ovarian Syndrome (PMOS) formerly known as Polycystic Ovary Syndrome (PCOS), characterized by hyperandrogenism, affects approximately 7.1–15.1% of women of reproductive age. While disease-causing CYP21A2 and CYP11B1 variants are well-studied, the contribution of synonymous variants to clinical and hormonal variations remains unclear. This study investigated whether synonymous and non-synonymous variants associated with phenotypic heterogeneity. Methods and results: A total of 275 premenopausal women (110 PMOS women and 165 healthy controls) underwent comprehensive clinical-biochemical evaluation. All exons and exon–intron boundaries of CYP21A2 and CYP11B1 were analyzed using direct sequencing. Genotype–phenotype associations were evaluated using non-parametric statistical tests and genetic model–based logistic regression analyses. Genotype and allele frequencies were similar between PMOS patients and controls; however, several variants showed distinct genotype–phenotype associations. Following false-discovery rate correction within predefined biological blocks, p.Val282Leu and non-classic congenital adrenal hyperplasia (NCAH)-related CYP21A2 variants remained significantly associated with elevated adrenocorticotropic-hormone(ACTH), while combined p.Leu9_Leu10insLeu/p.Arg103Lys/p.Ser269Thr/ p.Ser494Asn variants was linked to reduced ACTH. Carriers of NCAH-associated CYP21A2 allele exhibited significantly reduced sex hormone-binding globulin (SHBG) and higher modified Ferriman-Gallwey(FGS) levels. CYP21A2 synonymous p.Leu40=/p.Pro46 = variant associated with lower BMI. Additionally, combined CYP11B1 p.Leu75=/p.Asp82 = genotype remained significantly associated with reduced SHBG, while p.Arg43Gln/p.Ala386Val was associated with reduced FGS. Conclusion: The findings underscore the variant-specific and cumulative impact of CYP21A2 and CYP11B1 alterations on the adrenal axis and systemic androgen bioavailability. These results suggest that synonymous variants may actively modulate hormonal and clinical traits, contributing to the inter-individual variability of PMOS-related phenotypes independently of overt PMOS risk.

Gezer, Arzu; Sanlı, Fatma; Aslan, Haktan; Özkaraca, Mustafa; Baygutalp, Nurcan Kılıç; Sarı, Ebru Karadağ; Karatas, Omer Faruk; Üstündağ, Hilal

Background: Type 2 diabetes mellitus (T2DM) leads to neurological complications through multiple pathways. Black elderberry (Sambucus nigra, SN) is rich in bioactive compounds with potential neuroprotective properties. This study sought to evaluate the neural-protective potential of SN extract in STZ-diabetic rats using an integrated molecular, biochemical, and histomorphological approach. Methods: Forty male Sprague-Dawley rats were divided into four groups (n = 10/group): control (C; 0.9% NaCl), SN (0.040 g/kg body weight), diabetes mellitus (DM; streptozotocin 50 mg/kg), and DM + SN (streptozotocin + SN). The treatment period was 10 weeks. Brain tissue was analyzed for histopathological changes, caspase-3 expression, microRNA (miRNA) expression, and oxidative stress markers. Results: Histopathological examination revealed severe neuronal degeneration in the DM group, significantly attenuated in the DM + SN group (p < 0.001). Caspase-3 immunoreactivity was markedly increased in DM group compared to controls and significantly reduced by SN treatment (p < 0.01). In situ hybridization showed high ribonucleic acid (rno)-miR-124-5p and rno-miR-144-5p expression in C and SN groups, with reduced expression in DM group (p < 0.05). SN treatment moderated these changes in DM + SN group. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed decreased miR-124 expression in DM group, restored to control levels by SN treatment. Biochemically, SN extract reversed diabetes-induced changes in oxidative stress markers, decreasing malondialdehyde (MDA) levels while increasing glutathione (GSH) and nitric oxide synthase (NOS) levels (p < 0.01). Conclusions: SN extract exerted robust neuroprotective actions in the diabetic brain through apoptosis inhibition, miRNA profile restoration, and amelioration of redox imbalance, underscoring its therapeutic promise for diabetes-associated neuropathy.

Celebi, Ozgur; Celebi, Demet; Baser, Sumeyye; Genc, Sidika; Taghizadehghalehjoughi, Ali

Background: Campylobacter jejuni is one of the most common causes of bacterial gastroenteritis worldwide, and its increasing resistance to antibiotics highlights the urgent need for alternative therapeutic strategies. Methods: This study investigates the antibacterial, antibiofilm, anti-inflammatory, and wound-healing effects of bee venom-derived exosomes (BVE), alone and in combination with metronidazole, against Campylobacter jejuni. Exosomes were isolated from bee venom. Their morphology was confirmed using scanning electron microscopy. Antimicrobial activity was assessed using disc diffusion, minimum inhibitory concentration, minimum bactericidal concentration, and fractional inhibitory concentration methods. A fibroblast wound infection model was developed to evaluate the effect on cell viability (MTT assay), oxidative stress (TOS/TAC), cytokine release (IL-1β, IL-10), and apoptosis-related gene expression (BAX, BCL-2). Results: The results demonstrated that both BVE and metronidazole possess antibacterial and antibiofilm activity, with the combination treatment showing additive effect (inhibition zone: 20 mm, biofilm inhibition: 82.6%). The combined treatment significantly decreased oxidative stress markers and IL-1β levels, while increasing IL-10 and total antioxidant capacity. Gene expression analysis showed that the treatment reduced pro-apoptotic BAX levels and upregulated anti-apoptotic BCL-2 expression, contributing to improved cell survival and wound regeneration. Conclusion: Bee venom-derived exosomes, especially when combined with metronidazole, exhibit strong potential as an alternative or adjunct therapeutic approach against Campylobacter jejuni infection. These findings suggest that BVE may offer a novel strategy to combat antibiotic resistance and promote tissue repair in bacterial gastroenteritis.

Toraman, Emine; Kalın, Şeyda Nur; Bayındırlı, Kübra Nur; Günaydın, Şükran; Keleş, Fatmanur; Altay, Ahmet; Budak, Harun

Background: This study aimed to investigate the anticancer effects of lobaric acid (LA), a lichen acid, in MCF-7 cells. Our previous study demonstrated that LA exhibits anticancer effects by triggering apoptosis in MCF-7 cells. However, the relationship between this anticancer effect and the oxidative pathway and apoptosis mechanism has not been explained. In this study, the cytotoxic and anticancer effects of LA on MCF-7 cells were investigated through oxidative stress and thioredoxin system pathways. Methods and results: For this purpose, reactive oxygen species (ROS), reduced glutathione (GSH), and malondialdehyde (MDA) levels were measured in MCF-7 cells exposed to LA at a concentration of 44.21 µg/mL (IC50). Additionally, the activities, gene, and protein levels of SOD, CAT, GPx, GST, GR, and TrxR enzymes were evaluated. In addition, the expression levels of TXN and TXNIP genes were also analyzed. The results showed that LA increased ROS and MDA levels and decreased GSH levels. Antioxidant enzyme activities (SOD, CAT, GR, TrxR) and protein levels decreased compared to the control, while heterogeneous changes were observed in gene expression levels. Despite increased GPX gene expression, a decrease in enzyme activity and protein levels was observed. While no change in TXN gene expression was observed, protein levels were decreased. TXNIP protein levels were also decreased. Conclusions: The findings provide important data for evaluating lichen-derived compounds as potential anticancer agents targeting redox balance.

Calli, Aylin Orgen; Kurt, Kerem; Narli, Gizem; Kocabey, Duygu Unal; Yilmaz, Alpay; Ocal, Irfan; Yigit, Seyran; Yilmaz, Ismail

Aim: Dedifferentiated endometrial adenocarcinoma (DEAC) is a rare, aggressive subtype, accounting for 2% of all endometrial cancers. Poor survival in DEAC prompts the need for effective treatment modalities through better prognostic classification. MicroRNAs (miRNA) have essential roles in tumor angiogenesis, which might enable their use as novel biomarkers. In this study, we aimed to reveal the relationship between the expression of miRNA-21 and miRNA-143, which are associated with angiogenesis, and the prognosis of DEAC. Method: The study included six cases diagnosed with DEAC. The expression levels of miRNA-21 and miRNA-143 were detected by quantitative real-time PCR. Microvascular density (MVD) was measured by CD34 staining. All data and effects on survival were compared for statistical significance. Results: Six cases diagnosed with DEAC were included in the study. The percentage of undifferentiated components ranged from 50 to 90%. The second component of differentiated carcinoma was detected as endometrioid (3/5 grade I, 1/5 grade II, 1/5 grade III) in five cases and serous in one case. The mean MVD was 27 (range 17–44, SD 9.4). In three cases, miRNA-21 expression was down-regulated in neoplastic areas compared to non-neoplastic areas. On the contrary, it was found to be up-regulated in the remaining three cases. MiRNA-143 expression decreased in four cases and increased in two cases. Conclusions: Based on these findings, we found a significant irregular expression of miRNA-21 in DEACs. As in other cancers, angiogenesis is significantly associated with survival in DEACs. This study provides initial data for revealing possible implications of miRNAs as prognostic indicators in DEAC.

Öztürk, Halil İbrahim

Background: Turkey is a country with different geographical features and therefore it is extremely diverse in plant diversity. Tomato is one of the most important vegetables produced both in the world and in Turkey. In this study, it was aimed to determine the genetic diversity of 24 tomato genotypes collected from local farmers from “Center villages” and “Üzümlü” district in Erzincan province. Methods and Results: Morphological (qualitative and quantitative) and ISSR(Inter Simple Sequence Repeat)were used to determine genetic diversity among genotypes. Contribution rates of morphological properties to the first three main components differed. Genotype 24 was found to be higher than other genotypes with important quantitative morphological features such as fruit length, fruit width, fruit weight and soluble solid content (SSC). Considering the overall morphological traits, a wide variation was detected between genotypes. Genotypes were divided into 2 main groups according to the evaluation with molecular markers. According to the molecular findings obtained. The polymorphism rate ranged from 0 to 100% and the average polymorphism rate was calculated as 80%. Conclusions: Present findings revealed the diversity in tomato genotypes collected from Erzincan province and may constitute the bases for further breeding studies in tomato and will bring an integrity in tomato identification studies.

Un, Harun; Ugan, Rustem Anil; Kose, Duygu; Yayla, Muhammed; Tastan, Tugba Bal; Bayir, Yasin; Halici, Zekai

Aim: We aimed to investigate the effects of rasagiline on acute lung injury that develops in the sepsis model induced with the cecal ligation and puncture in rats. Main Methods: The rats were separated into the following six groups, Group 1: Sham, Group 2: Sham + Rasagiline 4 mg/kg, Group 3: Sepsis, Group 4: Sepsis + Rasagiline 1 mg/kg, Group 5: Sepsis + Rasagiline 2 mg/kg, Group 6: Sepsis + Rasagiline 4 mg/kg. A total of four holes were opened with a 16-gauge needle through the cecum distal to the point of ligation. Key Findings: Rasagiline treatment increased glutathione level and superoxide dismutase activity while decreased the malondialdehyde level after the sepsis. There was a statistically significant improvement in the doses of 2 mg/kg and 4 mg/kg. Rasagiline also increased Tnf-α, IL1β, IL6, NF-κβand HMGB1 gene expressions in dose-dependent at 2 mg/kg and 4 mg/kg doses. In increased doses, rasagiline prevent the development of edema, the formation of inflammation, and hemorrhage. Significance: Rasagiline exerts both antioxidant and anti-inflammatory effects on the cecal ligation and puncture induced acute lung injury in rats.

Ferah Okkay, Irmak; Okkay, Ufuk; Cicek, Betul; Yilmaz, Aysegul; Yesilyurt, Fatma; Mendil, Ali Sefa; Hacimuftuoglu, Ahmet

Background: This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. Methods and results: To establish Parkinson’s Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4′,6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. Conclusions: These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD.