Maltepe University

This study aimed to investigate the effects of Lavandula angustifolia oil and medical ozone on the gene expressions of CYP1A1, CYP1A2, CYP2B1, and CYP3A1, as well as on the levels of Malondialdehyde (MDA), and the activities of Superoxide Dismutase (SOD) and Catalase (CAT) enzymes on acute liver toxicity. Experimental groups were established by separating 10-week-old 28 Wistar male rats, each weighing between 350 and 450g, into four groups of seven rats each. Gene expression levels were determined using RT-qPCR. MDA measured in the tissue samples by the thiobarbituric acid method. SOD and CAT enzyme activities measured spectrophotometrically. CYP1A1 fold regulation significantly decreased in the Lavandula (p = 0.012), and medical ozone (p = 0.044) groups compared to the control group. However, changes in the combination group were not statistically significant compared to the control group (p = 0.133). There were no significant differences in the fold regulations of CYP1A2, CYP2B1, and CYP3A1 among any groups (p > 0.05). MDA levels were significantly lower in the Lavandula, and medical ozone groups compared to the control group (p = 0.001). CAT enzyme activity did not show significant differences in the Lavandula (p = 0.096) and medical ozone groups (p = 0.103) but decreased significantly in the combination group (p = 0.031). SOD enzyme activity did not show significant differences among the groups (p = 0.112). Lavandula and medical ozone treatments significantly reduced CYP1A1 gene expression and MDA levels, which may indicate their potential in reducing oxidative stress. These findings highlight the complexity of combined therapies and suggest possible interactions or suppressive effects between the agents, which have not been previously reported.

Abstract The growing need for enhanced thermal regulation in both electric and internal combustion engine vehicles has driven significant research efforts toward the development of next-generation heat exchanger technologies. Motivated by the pressing need for thermally consistent and high-fidelity prediction tools in contemporary automobile systems, this study introduces a novel hybrid framework by coupling empirical results from ZnO–water nanofluid experiments with physics-informed neural networks (PINN). This approach is crucial for connecting empirical data with fundamental physical rules for accurate thermal prediction. The experimental investigations were carried out across a range of operating parameters, including nanoparticle volume concentrations from 0 to 0.1%, inlet temperatures between 40 °C and 80 °C, and volume flow rates varying from 5 to 11 LPM. Major results revealed that the highest thermal enhancement was achieved at a ZnO concentration of 0.025%, which led to an increase of up to 213% in the convective heat transfer coefficient and a 214% improvement in the Nusselt number relative to pure water, particularly under low-temperature conditions. Beyond this concentration, performance deteriorated due to agglomeration and increased viscosity. Using the experimental data, both artificial neural network (ANN) and physics-informed neural network (PINN) models were developed to predict key parameters such as the Nusselt number and heat transfer coefficient. The PINN model outperformed the ANN, yielding approximately 7.6% higher R 2 for the heat transfer coefficient (0.9167 vs 0.8354) and 8.7% higher R 2 for Nusselt number predictions (0.8697 vs 0.7901). These findings highlight the importance of creating a high-fidelity digital twin architecture that addresses the ‘black-box’ constraints of traditional AI, offering a comprehensive solution for real-time optimization and monitoring of advanced automobile cooling systems.

Abstract Hybrid metal–polymer–two-dimensional (2D) semiconductor heterojunctions offer an effective platform for tailoring interface-controlled electrical and dielectric properties. In this study, Al/PANI–Silicene/n-Si Schottky diodes were fabricated and investigated using current–voltage, capacitance–voltage, admittance, and impedance spectroscopy over a wide frequency range. The devices exhibit clear rectifying behavior with an enhanced effective barrier height and reduced reverse leakage current, indicating relatively improved interface quality. Frequency-dependent measurements reveal strong dispersion in capacitance and dielectric loss at low frequencies, which gradually diminish at higher frequencies. Impedance and Nyquist analyses show a single dominant interfacial response, while modulus and dielectric representations indicate non-ideal relaxation behavior associated with a distributed spectrum of interface states. The extracted electrical parameters demonstrate that the incorporation of a Silicene interlayer significantly modifies the interfacial response of PANI-based Schottky junctions. These results provide a measurement-driven understanding of charge transport and dielectric behavior in polymer–2D–Si heterostructures and highlight their potential for advanced electronic device applications.

This paper examines the influence of key economic variables—gross domestic product (GDP), foreign direct investment (FDI), environmental tax revenues (ETR), and natural resource rents (NRR)—on progress toward the Sustainable Development Goals (SDGs) in Sub-Saharan Africa (SSA) for the period 2010–2023. To reflect the complex and multidimensional nature of sustainability, financial development (FD) and institutional quality (IQ) are included as control variables. Financial development (FD) and institutional quality (IQ) are included as control variables to capture the complex nature of sustainability. The empirical analysis employs fixed-effects panel models with Driscoll–Kraay standard errors to account for heteroscedasticity, autocorrelation, and cross-sectional dependence. To address potential endogeneity and dynamic relationships, the two-step system Generalized Method of Moments (System GMM) estimator is applied as a robustness check. The results indicate that GDP, ETR, and FD have statistically significant positive effects on overall SDG performance, while FDI inflows, NRR, and weak IQ exert substantial adverse impacts. Disaggregated findings show that GDP enhances progress on social and economic goals, but is insufficient to address environmental and institutional dimensions. ETR contributes positively to climate action, industrial development, and well-being, but negatively affects SDG 15 (life on land). FDI and NRR are associated with negative externalities, supporting the pollution haven and resource curse hypotheses. This paper is the first to assess the impact of these variables across all 17 SDGs in SSA, offering new insights into the region’s development dynamics. It provides critical implications for designing integrated policy strategies aimed at fostering inclusive growth, environmental sustainability, and institutional reform in alignment with the 2030 Agenda.

Letrozole and other aromatase inhibitors are increasingly recognized as first-line ovulation induction (OI) medications, offering an efficient and physiologic approach to ovarian stimulation that enhances outcomes in reproductive medicine. By selectively inhibiting aromatase and maintaining lower peripheral estrogen levels, letrozole supports mono- or bi-follicular development while reducing the risk of supraphysiologic estradiol exposure seen with traditional gonadotropin regimens. These pharmacological characteristics have contributed to its expanding use not only in OI but also in various assisted reproductive technologies. To evaluate the clinical benefits, effectiveness, and safety of using letrozole in in vitro fertilization (IVF), in vitro maturation (IVM), and OI, with particular attention to reproductive outcomes, ovarian response, endometrial effects, cycle characteristics, and treatment-related adverse events. A comprehensive systematic search covering the period from December 2000 to November 2025 was conducted across major electronic databases including PubMed, Embase, the Cochrane Library, and Google Scholar. The search strategy incorporated predefined keywords related to letrozole, aromatase inhibition, OI, IVF, and IVM. Studies involving randomized controlled trials, observational cohorts, and meta-analyses were included, while non-clinical and non-reproductive data were excluded. Relevant outcomes were extracted and synthesized qualitatively. Letrozole demonstrates broad clinical utility in reproductive medicine, spanning assisted reproductive techniques, ovarian stimulation strategies, and the management of ovarian hyperstimulation syndrome risk, ectopic pregnancy, and endometriosis-related infertility. Its targeted estrogen suppression, cost-effectiveness, and favorable safety profile make it a valuable component of individualized treatment protocols. Nonetheless, further high-quality research is required to refine optimal dosing strategies, identify ideal patient populations, and clarify long-term reproductive and obstetric safety.

Background: Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC) accounts for approximately 5% of metastatic CRC cases. Immune checkpoint inhibitors (ICIs) are the standard of care based on pivotal clinical trials; however, real-world data, particularly from low-resource countries, remain scarce, and prognostic factors are not yet fully defined. Therefore, we evaluated the efficacy and the safety of ICIs in a multi-center cohort. Methods: This multi-center retrospective study included 45 patients treated with ICIs across six oncology centers in Türkiye between June 2017 and December 2024. Patients received either anti-PD-1/PD-L1 monotherapy or anti-CTLA-4-based combination therapy. Key clinical variables and 1-, 2-, and 3-year OS and PFS outcomes were systematically collected. Results: The median age was 61 years, and most patients (75.6%) received ICIs in later treatment lines. After a median follow-up of 24.1 months, median OS and PFS were not reached. The estimated 1-, 2-, and 3-year OS rates were 82%, 76.1%, and 76.1%; PFS rates were 75.6%, 67.5%, and 67.5%, respectively. In multivariate analysis, an ECOG < 1 (HR: 0.072; 95% CI: 0.012-0.453; p = 0.005), a metastatic burden of fewer than two sites (HR: 0.211; 95% CI: 0.052-0.860; p = 0.030), and absence of antibiotic exposure within one month prior to immunotherapy initiation (HR: 0.145; 95% CI: 0.034-0.614; p = 0.009) were independently associated with improved overall survival. For PFS, ECOG < 1 (HR: 0.172; 95% CI: 0.052-0.573; p = 0.004), a metastatic burden of fewer than two sites (HR: 0.248; 95% CI: 0.078-0.788; p = 0.018), and no recent antibiotic exposure (HR: 0.209; 95% CI: 0.064-0.687; p = 0.010) remained independent predictors of prolonged survival. Conclusions: We observed overall survival outcomes similar to those reported in phase III clinical trials of immunotherapy in MSI-H/dMMR colorectal cancer, despite a substantial proportion of patients receiving immunotherapy in later lines of treatment. These findings support immune checkpoint inhibitors as the standard of care for MSI-H/dMMR metastatic colorectal cancer and emphasize the importance of improving access to immunotherapy, particularly in low-resource settings.

<title>Abstract</title> Breast cancer is among the leading causes of cancer mortality worldwide, with aging as a major risk factor. Caloric restriction (CR) is a well-established non-pharmaceutical intervention that extends healthspan and delays tumorigenesis, yet the systemic molecular mechanisms remain elusive. Both chronic and intermittent CR influence metabolic homeostasis, but their long-term effects on circulating miRNAs in breast cancer predisposition are unclear. Here, we examined how chronic and intermittent CR and subsequent refeeding remodel circulating miRNA networks in a tumor-free, breast cancer-prone transgenic mouse model. Blood samples were collected and circulating miRNA expression levels were determined at weeks 10 (baseline), 49 (adult), and 81 (old) using GeneChip miRNA 4.1 Array. Differential expression and target enrichment analysis were performed to identify age- and diet-associated modulatory patterns. Aging was associated with notable alterations in circulating miRNAs, and validated targets were enriched in the regulation of neurogenesis, MAPK, and FoxO signaling. Both chronic and intermittent CR reshaped these age-associated alterations, with the regulation of neurogenesis emerging as a key regulatory pathway. The effects were most pronounced at adult age rather than old age, while refeeding phase of the intermittent CR partially preserved the CR-induced miRNA patterns. Integrative analyses identified ten core miRNAs, where CR counteracted the expression patterns induced by aging, suggesting shared molecular mechanisms connecting aging, diet, and breast cancer risk. Our findings demonstrate that chronic and intermittent CR modulate circulating miRNAs in an age-dependent manner. These circulating miRNAs may act as systemic mediators linking to CR to neuroendocrine homeostasis and reduced breast cancer susceptibility.

BackgroundSqualene, a natural isoprenoid and an intermediate in cholesterol synthesis, has anti-inflammatory and skin-protective effects. The aim of the present study was to investigate the impact of squalene on the cellular viability of human gingival fibroblasts (HGF), and wound closure, the expression levels of transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), type-I and type-III collagen in an in vitro wound healing model.MethodsSqualene was used at concentrations of 10 µM (SQ1 Group) and 100 µM (SQ2 Group). The cell viability cytotoxicity to HGF was assessed using the MTT assay at 24, 48, and 72 hours. Scratch assay was used to evaluate wound healing at baseline, 24, 48, and 72 hours. The expressions of TGF-β, VEGF, type-I and type-III collagen were evaluated using the ELISA at 24, 48 and 72 hours.ResultsNo cytotoxic effects were observed in groups. A significant reduction in remaining wound area was observed in the SQ2 group at 24 hours and in both the SQ1 and SQ2 groups at 48 hours compared to the control group (p < 0.05). TGF-β was higher in the SQ2 group compared to the control group at 24 hours (p < 0.05), and at 48 hours, TGF-β levels in the SQ1 group were higher than both the control and SQ2 groups (p < 0.05). In type-I collagen, at 48 hours, both SQ1 and SQ2 groups exhibited higher levels compared to the control (p < 0.05). Type-III collagen levels were greater in the SQ1 group than in both the SQ2 and control groups at 48 hours (p < 0.05).ConclusionsConsidering its non-cytotoxic profile on HGF and its effects on TGF-β, type-I, and type-III collagen expression, squalene appears to facilitate wound healing by promoting wound closure.