Ozdemir Sarikaya, Bengul; Gul, Huseyin Fatih; Gozcu, Sefa; Yayla, Muhammed

The present study aimed to investigate the therapeutic effects of Malus floribunda fruit ethanol extract on metabolic parameters and insulin signalling in a letrozole-induced PCOS-associated insulin resistance model. 60 female Sprague-Dawley rats were randomly allocated into five groups: Healthy Control, IR, IR + Metformin (300 mg/kg), IR + MF250, and IR + MF500. Treatments were administered orally for 15 days. Fasting insulin, HOMA-IR, OGTT, lipid profile, and reproductive hormones were assessed. Histological and IHC analyses of InR, IRS-1, and IRS-2 were performed on muscle and adipose tissues. The IR group exhibited significantly elevated insulin (p<0.001), HOMA-IR (p<0.001), testosterone, triglycerides, LDL, and total cholesterol levels, with reduced HDL and oestrogen levels compared to controls. Treatment with M. floribunda, particularly at 500 mg/kg, significantly improved insulin levels (p<0.001), HOMA-IR (p<0.001), lipid profile, and hormonal parameters. IHC analysis revealed suppressed InR, IRS-1, and IRS-2 expression in muscle and adipose tissues of the IR group, which was restored following M. floribunda treatment. M. floribunda extract administration, particularly at 500 mg/kg, significantly improved glucose homeostasis, lipid metabolism, hormonal balance, and insulin signalling pathway components (InR, IRS-1, IRS-2) in a letrozole-induced PCOS-associated insulin resistance model. These findings suggest that M. floribunda may serve as a promising alternative therapeutic agent for insulin resistance management.

Erkmen Doǧru, Tuǧba; Gülfidan, Gizem; Ateş, Halil; Arga, Kazlm Yalçln; Koçtürk, Semra

Objectives: Acute myeloid leukemia (AML) is a severe blood cancer with less than 50% long-term survival. Despite advancements in treatment options, relapse is still the major obstacle. The main reason of this problem is ineffective targeting of leukemic stem cells (LSCs), which play an important role in tumor development and relapse. In our previous studies, we found that casticin, the major polyphenolic component of Vitex trifolia's fruit, targets both leukemic cells and LSCs without affecting healthy tissues. Therefore, in this study, we aimed to investigate the effect of casticin-mediated cell death in relation to the LSCs-favored survival pathways at gene and protein expression levels using in vitro LSC-like and parental leukemic cell models. Methods: We validated the LSC character of KG1a and KG1 cells (84.55% CD34+, CD38- and 93.55% CD34+, CD38+, respectively) by flow cytometry. For the investigation of casticin's mechanism of action, we employed real time-PCR, western blotting and bioinformatics analyses. Results: Our results showed an increase in cleaved PARP/β-actin ratio but no change in LC3BI/II and SQSTM/β-actin ratios. Our gene expression, bioinformatics and immunoblotting analyses represented significant decrease in Shh, Gli and Wnt levels. We also elucidated a possible crosstalk between Hedgehog and other oncogenic cascades via the Gli, Notch, YAP, p38, Mcl-1, and Myc proteins in casticin mediated anti-leukemic effect. Conclusions: In conclusion, we found that casticin induces apoptosis in both LSC-like and parental leukemia cells mainly by suppressing Shh signaling, which is crucial for LSC survival and AML relapse.

Akyel, Hilal; Bahador Zırh, Elham; Zırh, Selim; Yazgi, Hare; Tel, Banu Cahide

Objectives: Alpha-synuclein (α-syn) fibrils, which are associated with Lewy-like inclusions, are currently utilized in the modeling of Parkinson’s disease (PD). The fibrils require a length shorter than 100 nm to uptake intracellularly. Our study aims to determine the optimal probe sonication parameters that can be applied in diverse laboratory settings for the fragmentation of fibrils to lengths of ≤100 nm. Methods: In our study, human wild-type α-syn fibrils were sonicated with 1, 3, and 5 s-on/off pulse applications at varying ambient temperatures (room temperature, ice, and ice-surrounded by dry ice) for a duration of 1 min, with a total of 40 and 60 cycles, respectively. The length of the fibrils was quantified by transmission electron microscopy imaging. The total α-syn in SH-SY5Y cells was detected by immunofluorescence staining following the administration of fragmented fibrils after 2-, 4-, and 6-day incubations. Results: Although fragmentation was observed under all conditions, fibrils of ≤100 nm were obtained with a 5 s-on/off pulse in ice and ice-surrounded by dry ice ambientes. The fibril length of ≤100 nm was observed on days 2 and 4; however, the highest level of observed intensity was detected on day 6. Conclusions: The application of 5 s-on/off consecutive pulses in ice, and ice-surrounded by dry ice ambientes are more effective methods for fragmenting and internalizing fibrils, thereby forming a reproducible cellular PD-like model. In summary, our study provides a significant contribution to the development of an economical and effective sonication methodology for the fragmentation of fibrils in a diverse of laboratory settings.

Sahin, İbrahim; Eroksuz, Yesari; Ugur, Kader; İncili, Canan Akdeniz; Eroksuz, Hatice; Aydin, Gizem Nur; Ozpolat, Emine; Bildirici, Furkan; Aydin, Suleyman

Objectives: It has been recently reported that immune activity of some animal peptides/proteins has been found in some plants. In this study, the presence of immune reactivity of alarin, asprosin, paraoxonase, elabela, glucagon, and nesfatin-1 like molecules was investigated in two plant species related to Kastamonu Taşköprü garlic (an endemic cultivar of the Allium sativum L.) and Tunceli garlic (Allium tuncelianum). Methods: Ten Kastamonu and 10 Tunceli garlic were embedded in paraffin blocks and 4–5 μm transversal and longitudinal sections were taken and stained by immunohistochemical method. In addition, 500 mg of wet tissue samples were homogenized from these garlic and supernatants were obtained. The amounts of alarin, asprosin, elabela, glucagon and nesfatin-1 were studied by enzyme linked immunosorbent assay (ELISA) method and paraoxonase was studied by spectrophotometric method. Results: Studied molecules show immune reactivity in the cytoplasm of the bulb storage cells of the plants parenchyma. The ELISA supernatant results also confirmed the presence of these animal molecules in the plants. Conclusions: Although we cannot reveal the purpose of the presence of these animal molecules detected in plants with these existing data, we predict that these data will be a source of inspiration in the field of botany, that studies will shift in this direction and that they might contribute to the revision of the evolutionary processes of all living things, especially an ancestor of garlics.

Aydin, Suna; Ugur, Kader; Yalcin, Hanifi; Sahin, İbrahim; Akkoc, Ramazan Fazil; Yakar, Burkay; Yucel, Dogan; Aydin, Suleyman

COVID-19 is the most devastating pandemic situation we have experienced in our age, affecting all systems. Although it affects all systems, it shows its most important effect through thrombophilia. Therefore, the possible cause of sudden death due to COVID-19 may be embolism caused by thrombophilia. D-dimer amounts increase due to COVID-19. The thrombosis is associated with sudden death in COVID-19 disease in populations. Since individuals with thrombophilia will be more prone to death due to COVID-19, it may be appropriate to administer low doses of Clexane (Enoxaparin sodium) or low-weight heparin for prophylactic purposes in order to consider these individuals at high risk and to prevent deaths. Moreover, in order not to risk the lives of healthcare professionals with thrombophilia, it would be appropriate to keep them away from individuals with COVID-19 disease and to employ them in different healthcare services according to their fields of expertise. It should also not be forgotten that different symptoms related to COVID-19 appear day by day, these different symptoms probably show that the virus has undergone mutations in order to survive, but no matter what, its effect on thrombophilia has not been eliminated yet. This compilation aims to present the reasons and causes of death due to COVID-19, possible treatment options, and thrombophilia panel tests and new parameters that may have a place in the meticulous interpretation of these tests and possible etiopathology in the light of current information. Therefore, presenting this information in a rational manner and keeping the parameters of the thrombophilia panel under strict control predict that the deaths due to the virus will be partially reduced.

Oruc, Yavuz; Aydin, Suleyman; Akkoc, Ramazan Fazil; Aydin, Suna; Gul, Fatih Cem; Ugur, Kader; Sahin, İbrahim; Hanbeyoglu, Onur; Sirri Kilic, Suleyman; Aksoy, Aziz

Objectives: We compared the laboratory and clinical symptoms of coronavirus disease 2019 (COVID-19), other viral (beside COVID-19), and bacterial conjunctivitis patients with the values of controls. Methods: Twenty COVID-19, 15 other viral, 15 bacterial patients, and 15 control group were included in the study. COVID-19 was diagnosed with the real time reverse transcription–polymerase chain reaction while the indirect immunofluorescent antibody test was used in the detection of other viral agents. Bacterial agents were determined with the detection of the agent. The ophthalmologic examination of all cases was carried out by direct penlight, and the anterior segment evaluation was performed. The laboratory findings of all cases included in the study were obtained from the hospital records. Results: It was determined that 5% conjunctivitis and 5% diplopia developed in patients diagnosed with COVID-19, 20% conjunctivitis developed in patients due to other viral agents, and 66.6% conjunctivitis developed in patients due to bacterial agents. Conclusion: The incidence of conjunctivitis in COVID-19 patients was lower than in other viral and bacterial groups. Neutrophil/lymphocyte ratio and C-reactive protein come to the forefront as precious parameters with high specificity and sensitivity that might be useful to distinguish these diseases.