Feyzan Özdal Kurt

Amaç: Meme kanseri, kadınlarda en sık görülen malignite olup kansere bağlı ölümlerin başlıca nedenlerinden biridir. Bu çalışmanın amacı, yeni bir benzoksazol türevi sentezlemek, farklı meme kanseri hücre hatlarında antikanser potansiyelini değerlendirmek ve bileşiğin NF-κB ile apoptozla ilişkili genler (APAF-1, sitokrom C, kaspaz-3 ve BCL-2) üzerindeki etkilerini Gerçek Zamanlı Polimeraz Zincir Reaksiyonu (Real-Time PCR) yöntemiyle araştırmaktır. Gereç ve Yöntem: Yeni sentezlenen benzoksazol türevi, insan meme kanseri hücre hatları olan MCF-7 ve MDA-MB hücrelerine uygulanmıştır. Bileşiğin sitotoksik etkisi MTT testi ile değerlendirilmiş, NF-κB ve apoptozla ilişkili genlerin (APAF-1, sitokrom C, kaspaz-3 ve BCL-2) ekspresyon düzeyleri ise Real-Time PCR yöntemi kullanılarak analiz edilmiştir. Bulgular: Sentezlenen 5-amino-2-(p-bromofenil)benzoksazol bileşiğinin kimyasal yapısı elemental analiz, kızılötesi spektroskopisi (IR) ve kütle spektrometrisi ile doğrulanmıştır. MCF-7 ve MDA-MB hücre hatlarında yapılan analizlerde, bileşik uygulaması sonrasında BCL-2 ekspresyonunun MCF-7 hücrelerinde kontrol grubuna göre arttığı, MDA-MB hücrelerinde ise azaldığı saptanmıştır. Sitokrom C ekspresyonunun MCF-7 hücrelerinde arttığı, buna karşın MDA-MB hücrelerinde kontrol grubuna kıyasla anlamlı bir değişiklik göstermediği belirlenmiştir. MTT analizi, sentezlenen bileşiğin her iki meme kanseri hücre hattında da sitotoksik etki oluşturduğunu ortaya koymuştur. Sonuç: Bulgularımız, yeni sentezlenen 5-amino-2-(p-bromofenil)benzoksazol türevinin özellikle MCF-7 hücre hattında apoptozla ilişkili yolakları düzenleyerek antikanser etki gösterebileceğini düşündürmektedir. Apaf-1 ve BCL-2 ekspresyonundaki değişiklikler ile birlikte gözlenen sitotoksik etki, bu bileşiğin meme kanseri tedavisinde potansiyel bir terapötik ajan olarak değerlendirilebileceğini göstermektedir. Ancak etki mekanizmasının ayrıntılı olarak ortaya konulabilmesi için in vitro ve in vivo düzeyde ileri çalışmalara ihtiyaç vardır.

Microbial colonization is a major factor contributing to peri-implantitis, and creating durable glassy surfaces with antimicrobial agents such as silver and copper may reduce microbial accumulation on dental abutments. This study aimed to develop antimicrobial thin-film glassy surfaces on Ti6Al4V alloy and to evaluate their surface and mechanical properties, antimicrobial effectiveness, and biocompatibility before and after thermal aging. A sol–gel-derived glassy matrix (G) was synthesized, and two antimicrobial coatings were prepared by incorporating ionic Ag (GAg) or a combination of Ag/Cu (GAgCu). Ti6Al4V specimens; these were either left uncoated or dip-coated with G, GAg, or GAgCu and cured at 450 °C. Half of the specimens underwent thermal aging between 5 °C and 55 °C for 3000 cycles. Surface roughness, contact angle, hardness, adhesion strength, scratch resistance, cytotoxicity (Agar diffusion and MTT assay on L929 fibroblasts), and microbial adhesion were evaluated using Streptococcus sanguinis, Porphyromonas gingivalis, and Candida albicans as representative oral microorganisms. Both coatings exhibited low surface roughness, hydrophilic surfaces, improved hardness, and significantly reduced microbial adhesion for all tested species. GAg showed superior mechanical properties, whereas GAgCu demonstrated a relatively stronger antimicrobial effect. Cytotoxicity tests indicated that all coatings were biocompatible at levels suitable for oral use. Overall, these coatings demonstrated strong adhesion, durability, and antimicrobial activity, suggesting their suitability for dental abutments made of Ti6Al4V.

Aquilaria agallocha Roxb. has traditionally been used to treat various medical conditions, including inflammation, fever, and cardioprotection. However, limited studies have explored its specific effects on cancer cells while distinguishing its impact on normal cells. This study aimed to evaluate the effects of A. agallocha heartwood extracts on both normal and cancer cells. To achieve this, mouse L929 (normal), 67NR, and 4T1 (cancer) cells were treated with methanol and ethanol extracts of A. agallocha heartwood to assess cytotoxicity, apoptosis, and oxidative stress. Flow cytometry analysis revealed that both extracts induced apoptosis and oxidative stress in all tested cell lines. However, the extracts exhibited a greater cytotoxic effect on normal L929 cells, potentially due to their bioactive components exerting a stronger pro-oxidant effect. These findings suggest that A. agallocha extracts may differentially affect normal and cancer cells, highlighting the need for further investigation into their selective cytotoxicity.

Many animal and human studies indicate that boric acid and calcium fructoborate have effects on helper T cells in immunity. The aim of our study is to evaluate the effects of boric acid and calcium fructoborate on Treg (CD4⁺Foxp3⁺) and Th17 (CD4⁺Ror-γt⁺) cell populations and related cytokine levels in mononuclear cells isolated from peripheral blood samples of rheumatoid arthritis and systemic lupus erythematosus patients. Newly diagnosed rheumatoid arthritis (n = 10) patients, systemic lupus erythematosus (n = 5) patients, and healthy individuals (n = 9) were included in this study. Consent forms were obtained from all individuals participating the study, blood samples were taken, and peripheral blood mononuclear cells were isolated. Isolated cells were exposed to low-dose and high-dose boric acid and calcium fructoborate in cell culture. Treg and Th17 cell populations were analyzed by flow cytometry after 48 h of exposure. IL-2, IL-6, IL-17, IL-23, TNF-α, and TGF-β levels in the culture medium were tested by ELISA method. At the end of the study, in healthy controls, high-dose BA improved the Treg/Th17 population but could not display similar effects on RA and SLE group. However, both boric acid and calcium fructoborate at different doses showed an increasing effect on Ror-γt in RA and SLE group. Different doses of BA and CaF treatment found to have a variable effect on cytokine. Both BA and CaF in low doses decreased TNF-α levels in RA group which shows that these boron compounds could contribute positively to the treatment of autoimmune diseases.

Cancer has become one of the most critical health issues, with an increasing incidence and mortality in recent years. Meanwhile, many studies are carried out on discovering new compounds which reflects effective results on cancer cells. Therefore, this study aimed to examine the cytotoxic, anti-proliferative and apoptotic effects on cancer cell lines by using the extract obtained from Uludağ Fir ($\textit{Abies nordmanniana subsp. bornmülleriana Mattf }$) resin. Uludağ Fir resin extract was obtained by applying the methanol extraction method. In our study, fibroblast cell L-929, human metastatic prostate cancer PC-3 and human metastatic prostate cancer DU-145 cell lines were cultured in RPMI-1640 medium. The effects of the resin extract concentrations on the viability of the cells were determined with the Muse™ Cell Count & Viability test. In addition, apoptosis and cell cycle phases of the cells were determined using the Muse™ cell analyzer. Finally, RT-qPCR analysis was performed to determine the resin extract effect on pro-apoptotic and anti-apoptotic gene expression. The apoptotic effect of Uludağ Fir resin extract on cancer cell lines was significantly higher in contrast to the healthy normal cells. In addition, it was determined that Uludağ Fir extract caused G0/G1 cell cycle arrest in cancer cells. In RT-qPCR analysis, the pro-apoptotic gene expression levels were apparently increased in cancer cells, which was followed by a decrease in the anti-apoptotic gene expression levels. All taken together, these results indicate that Uludağ Fir resin extract exerts two prong effects as it induces a cell cycle arrest and apoptotic pathway activation on human prostate cancer cell lines.

AIM: Colon cancer is one of the main health problems worldwide. Cancer stem cells (CSCs) are referred to as tumor-initiating cells involved in tumor heterogeneity and dormancy. CSCs can cause drug resistance, metastasis, and recurrence of primary and metastatic cancers. The interactions and survival trends of colon cancer stem cells with other cells may be an alternative route for effective treatment. In our study, we aimed to evaluate the effects of asteoside on stem cell properties, apoptotic and inflammatory processes in primary (HCT-116) and metastatic (Colo-741) colon CSCs. METHERIALS AND METHODS: CSCs were obtained from both types of colon cancer cell lines with the MINIMACS system using the anti-CD133 reagent. Metastatic Colo-741 and non-metastatic HCT-116 CD133+ and CD133- cells were cultured with or without Acteoside for 48 hours. Expressions of Caspase-3, Bcl, Bax, and Fas-L for apoptosis, and IL-1β, TNF-α, IL-6, IL8 and IL-10 for inflammation were analyzed by indirect immunocytochemistry technique by performing H-Score. Changes in cell morphology were examined under an inverted microscope. RESULTS AND CONCLUSION: It was observed that Oct-4 expression decreased after acteocyte administration in both metastatic and non-metastatic colon cancer cells. In addition, Colo-741 increased the intensity of the Bax/Bcl ratio in both CD133+ and CD133- cells and increased caspase 3 expression. While acteoside did not immunohistochemically affect inflammation in metastatic COLO-741 cells, it contributed to the apoptotic process by changing the Bax/Bcl ratio. When the morphology of the cells was evaluated, it was observed that the number of apoptotic cells increased in COLO-741 CD133+ and CD133- cells.

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.

Among chemotherapeutic agents, cisplatin and the other platinum-based drugs have occupied for 35 years an enviable position. The limitations of platinum-based drugs, dose dependent side effects and development of drug resistance mechanisms, have boosted the research for finding other metal-based drugs. Among metals, ruthenium is probably the one showing the greatest promises. Ruthenium (Ru) appears to be less toxic than platinum and several biological studies have indicated that ruthenium complexes possess diverse modes of action. The redox chemistry of ruthenium is rich and compatible with biological media, and the overall toxicity of ruthenium is lower than platinum, thus allowing higher doses of treatment. In this study we aimed that, analyses of different type of ruthenium complexes in cancer cell lines. Six Ru complexes were determined by elemental analysis, FTIR, NMR, UV-visible spectroscopy, electron density on the metal was measured by cyclic voltammetry. After that, the cellular properties of this complexes were analyses on PC-3, HT-29, Du-145 and Vero cell lines. DNA damage was analyzed H2AX staining, apoptotic cell analyses were performed flow cytometry and western blotting. After 48 h incubation of Ru complexes three of them more effective for cell lines. Especially Ru3 was more effective in cancer cell lines. Apoptotic pathway was triggered after Ru complexes incubation in PC-3, Du-145 and Ht-29 cancer cell lines. Our study suggest that Ru complexes may be used for cancer cell cytotoxicity as a drugs in patients.

Colorectal cancer, as one of the main health problems worldwide. Cancer stem cells (CSCs) are called tumor-initiating cells involved in tumour heterogeneity and dormancy. CSCs may cause drug resistance, metastasis and relapse of primary and metastatic cancers. Dysregulation of survive and their cross-talk with other cell pathways may alternative way for effective treatment. We aimed whether acteosid, affects stemness and inflamatuvary prosess in primary (HCT-116) and metastatic (Colo-741) colon CSCs. CSCs were obtained from both type of colon cancer cell lines using MINIMACS system using anti-CD133. CD133+ and CD133- cells from Colo-741 and HCT-116 were cultured without or with Acteosid for 48 h. Distribution of Caspase-3, Bcl, Bax, IL-1β, TNF-α, IL-6, IL8 and IL-10 analyzed using indirect immunohistoperoxidase technique. Acteosid increased the intensity of Bax/Bcl ratio on CD133+, CD133- Colo-741 cells, there wasn’t differences of Caspase-3 immunoreactivity. Oct-4 was also decreased in CD133+ and CD133- Colo-741 cells. Caspase 3 was slightly increased CD133+ cells after incubation with Acteoside. In conclusion, it has been observed that the viability and stemness of the HCT-116 was increased after Acteoside, these properties were not changed in CD133+ Colo-741 cells. Therefore inhibition of ROS may play a role during CSCs stemness and viability.