Sevgi Yardim-Akaydin

Investigation of the Effect of Calcitriol on Radiofrequency Radiation-Exposed Breast Cancer Cell Lines - Turkish Journal of Pharmaceutical Sciences

The triterpenoid and polysaccharide constituents of Ganoderma lucidum (GL) are believed to influence key pathogenic pathways in Alzheimer’s disease (AD). This study first examined the molecular rationale for GL’s neuroprotective properties by subjecting its principal triterpenoids, Ganoderic Acid A&B, to computational profiling. Molecular docking was performed against human acetylcholinesterase (AChE), TNF-α, COX-2, IL-6, caspase-3, Bcl-2, and the Keap1–Nrf2 complex using CB-Dock2, alongside SwissADME-based physicochemical and ProTox-3.0-based toxicological screening. These targeted pathways were then biologically validated in an in vitro AD model induced by Aβ_1–42 toxicity in SH-SY5Y cells, assessing AChE activity, apoptosis, ROS levels, mitochondrial membrane potential (MMP), and cytokine expression (COX-2, TGF-β1, IL-6, TNF-α, IL-10). Docking revealed high binding affinities of both triterpenoids toward all seven targets (Vina scores: −7.3 to −10.4 kcal/mol), predicting strong modulation of cholinergic, inflammatory, apoptotic, and antioxidant pathways. Consistent with these predictions, GL extract significantly reduced TNF-α, COX-2, and IL-6 mRNA and protein levels, attenuated ROS accumulation, preserved MMP except at 500 µg/mL, and exerted a concentration-dependent antiapoptotic effect. IL-10 and TGF-β1 showed complex, dose-dependent patterns, reflecting indirect regulatory responses. Together, these findings support GL’s neuroprotective potential against Aβ-induced toxicity through direct engagement of cholinergic, inflammatory, apoptotic, and antioxidant regulatory proteins.

Alzheimer's disease (AD) is a progressive, chronic disease characterized by impaired cognitive function. Currently, there is no complete cure for ad; current treatments are aimed at reducing symptoms and slowing the progression of the disease. It is thought that the amount of fatty acid consumption and the balance between them may be protective against neurological diseases. In this study, it was aimed to determine the protective effects of Ω3/Ω6 polyunsaturated fatty acids ratios in Aβ1–42-induced ad model in human neuroblastoma (SH-SY5Y) cells. The viability of cells was determined by MTT assay. The percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI. ROS, MMP and cell cycle analysis were performed by flow cytometry. The amount of acetylcholinesterase enzyme was measured with a commercial kit. 48 h after the application, a statistically significant decrease was observed in the MTT test in the 1/1, 1/2 and 1/8 groups and in the amount of AChE in the 1/4, 1/8 and 1/16 groups. According to apoptosis findings, all ratios were observed to reduce cell viability compared to the control group. ROS and MMP levels were detected to decrease in all groups compared to the control group. The highest neuroprotective effect against oxidative stress was observed at 1/1 dose. Aβ1–42 induced blockade of the cell cycle was observed to be partially corrected by 1/8 dose. As a result, it can be said that Ω6 and Ω3 fatty acids, when used in 1/4 and 1/8 doses can provide a protective effect against Alzheimer's disease.

Investigation of the Effects of Polyunsaturated Fatty Acid Ratios in Human SH-SY5Y Cells by in vitro Methods - Turkish Journal of Pharmaceutical Sciences

Objective: Obesity is defined as excessive increase in adipose tissue in the body. Adipose tissue also provides the secretion of adipokine hormones such as leptin, adiponectin, asprosin and apelin, which play an important role in metabolism and energy homeostasis. For this reason, changes in the levels of these adipokine hormones secreted from the adipose tissue, not the increase in adipose tissue alone, are effective in determining childhood obesity and explaining the pathological mechanisms. Evaluation of these polypeptides will be effective in the diagnosis of obesity and elucidating the pathological mechanisms associated with obesity. Material and Method: In our study, it was conducted to reveal the relationship of obese children with some markers of obesity such as serum leptin, adiponectin, asprosin and apelin levels, and blood lipids, fasting blood glucose and insulin resistance index (HOMA-IR) values. 105 obese children and 38 normal weight children participated in our study. The demographic information of the children was determined by the face-to-face survey method. Leptin, adiponectin, asprosin and apelin levels were determined in morning fasting blood samples from obese and normal weight children with the help of commercial Elisa kit. Result and Discussion: Leptin and adiponectin levels were not different in obese and normal weight children (p>0.05). Asprosin and apelin levels were found to be significantly higher in obese children compared to normal weight children (p<0.001). Positive correlations were observed between adipokine hormones in both obese and normal children. The ratios of leptin/asprosin, leptin/apelin, adiponectin/asprosin, adiponectin/apelin, asprosin/apelin were found to be statistically significantly lower in obese children when compared with normal weight children (p<0.05). In our study, high levels of asprosin and apelin, which have conflicting results in the literature, and positive correlations between adipokine hormones can be considered as important findings.

Polycystic ovary syndrome (PCOS) is a chronic and heterogeneous disease associated with obesity, hyperinsulinemia, dyslipidemia and chronic low-grade inflammation. Adipsin is a protein that is mostly secreted from adipose tissue and is a structural homolog of complement factor D, the rate-limiting enzyme of the alternative complement system. The aim of this study was to investigate adipsin levels in adolescents with PCOS and their relationship with obesity. 40 normal weight--children with PCOS and 40 obese-children with PCOS, and 40 normal weight healthy children participated in our study. Adipsin levels of adolescents in each group was measured in morning fasting blood samples by a commercial ELISA kit. Adipsin levels showed statistically significant differences between the groups. (p<0.001). Normal-weight PCOS adolescents had higher adipsin levels than both obese PCOS and healthy controls. A negative correlation was observed between adipsin levels and BMI in the PCOS group (r=-0,457, p<0,001). In conclusion, adipsin can be considered as an independent risk factor in normal weight adolescents with PCOS and may help in the diagnosis of PCOS in normal weight children with other symptoms.

Radiofrequency (RF) fields have been classified as probable human carcinogens and non-thermal RF-radiation (RFR) can cause an increase in oxidative stress and inflammation in tissues. Vitamin D has been researched for many years for its anti-cancer and suppressive effects on cancer cell growth. In this study, we aimed to examine the effects of exposure to RF signals on cell viability, free radical formation, and related inflammation, and the restorative effect of vitamin D against this. For this purpose, MCF-7 and MDA-MB-231 cells were exposed to 2.1GHz W-CDMA-modulated RFR. The viability of cells was determined by MTT assay, and the percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI assay. The expression levels of VDR, NF- κB, COX-2, and p53 genes were studied using Real-Time-PCR. ROS analysis was performed by flow cytometry. A statistically significant decrease in MCF-7 cell viability (p < 0.001) was observed with increasing doses of calcitriol compared to the control group, while no significant difference was observed in MDA-MB-231 cells (p > 0.05). As a result of ROS analysis, significant decreases in life values were observed for both cells due to calcitriol. A statistically significant increase in p53 expression was observed with increasing calcitriol dose in both cell lines. An increase in VDR, NF-kappa B, and COX2 expressions was also observed in MCF-7 cells. We observed that calcitriol administered after RF exposure caused an increase in apoptosis and mRNA expression of inflammation markers, a decrease in ROS levels, and an increase, and this can be evaluated in cancer treatment or prevention.

Amaç: Bu araştırmada Düzce'de halk ilacı olarak kullanılan yedi bitkinin [Dioscorea communis (L.) Caddick & Wilkin, Mentha longifolia (L.) L. subsp. typhoides (Briq.) Harley, Origanum vulgare L., Rubus ulmifolius Schott, Salvia tomentosa Mill., Thymus longicaulis C.Presl subsp. longicaulis, Trachystemon orientalis (L.) D. Don] üreaz, kimotripsin inhibe edici ve antioksidan aktivitelerinin tespiti amaçlanmıştır. Gereç ve Yöntem: Bu amaçla bitkilerden metanol ve su ekstreleri hazırlanmıştır. Daha sonra in vitro üreaz ve kimotripsin inhibitör aktiviteleri belirlenmiştir. Ayrıca farklı yöntemlerle antioksidan aktiviteleri (ABTS, CUPRAC, DPPH), toplam fenol ve flavonoit içerikleri de tespit edilmiştir. Sonuç ve Tartışma: D. communis, O. vulgare, S. tomentosa ve T. longicaulis'in metanol ekstreleri orta düzeyde üreaz inhibitör aktivite (%34.26 ile %44.94 aralığında inhibisyon) gösterirken, diğerlerinde aktivite daha düşük bulunmuştur. En güçlü kimotripsin inhibe edici aktivite R. ulmifolius metanol ekstresi ve T. orientalis su ekstresinde gözlenmiştir (IC50 değerleri sırasıyla 65.32 ve 78.65µg/ml). Genel olarak, çalışılan bitkiler yüksek fenol ve flavonoit içeriklerine uygun olarak yüksek antioksidan aktivite göstermiştir. Sonuç olarak R. ulmifolius ve T. orientalis kuvvetli kimotripsin inhibe edici aktiviteleri ile dikkat çekmiştir. Bu bitkilerin kimotripsin aktivitesi üzerinde daha kapsamlı çalışmaların yapılması gerekmektedir.

Amaç: Bu araştırmada Malva neglecta Wallr.’nın kimotripsin ve üreaz enzimlerini inhibe edici aktivitesinin tespiti ve ayrıca antioksidan aktivitesi, toplam fenol ve flavonoit içeriğinin belirlenmesi amaçlanmıştır. Yöntem: 2021 yılı Nisan-Haziran ayları arasında bitkinin çiçekli ve meyveli toprak üstü kısımlarından metanol ve su ekstresi hazırlanmış ve bu ekstrelerin in vitro üreaz ve kimotripsin inhibitör aktivitesi belirlenmiştir. Antioksidan aktivitenin tespiti için ABTS, CUPRAC ve DPPH yöntemleri kullanılmıştır. Toplam fenol ve flavonoit içerikleri ise sırasıyla Folin Ciocalteu ve aluminyum klorür kolorimetrik yöntemleri kullanılarak belirlenmiştir. Bulgular: Metanol ekstresi önemli düzeyde kimotripsin inhibe edici aktivite göstermiştir (IC50: 67.67 µg/mL); üreaz enzimi üzerinde ise hem su hem metanol ekstresi orta düzeyde inhibe edici etki göstermiştir (sırasıyla %36.52 ve 34.38 inhibisyon). DPPH ve CUPRAC testlerinde metanol ekstresi daha yüksek antioksidan aktivite sergilerken; ABTS testinde su ekstresi daha yüksek radikal süpürücü aktivite göstermiştir. DPPH ve CUPRAC testlerinde elde edilen sonuçlarla paralel olarak metanol ekstresinin flavonoit içeriğinin daha yüksek olduğu anlaşılmıştır (42.93 mg rutin eşdeğeri/g). Sonuç: Sonuç olarak M. neglecta kuvvetli kimotripsin inhibe edici aktivitesi ile dikkat çekmiştir. Üreaz inhibe edici aktivitesi ve flavanoit içeriğiyle paralel antioksidan aktivitesi de dikkate alındığında bitki üzerinde daha kapsamlı çalışmaların yapılması gerektiği sonucuna varılmıştır.