Ferhunde Aysin

Magnetic nanoparticles (NPs) are maintained in the body for a significantly longer duration than small molecule antibiotics, potentially facilitating prolonged therapeutic effects. In this study, a novel nanoantibiotic formulation ( l ‐glu–Fe ₃ O ₄ –Amp NPs) was prepared, and its antibacterial efficacy was evaluated. For this purpose, l ‐glutamic acid ( l ‐glu) was used for surface modification of iron oxide nanoparticles (Fe ₃ O ₄ NPs), and ampicillin (Amp) was then conjugated l ‐glu–Fe ₃ O ₄ NPs structure. Fourier transform infrared analyses revealed that the final nanoantibiotic formulation l ‐glu–Fe ₃ O ₄ –Amp NPs was successfully prepared. The size distribution of the formulation was determined to be 164 nm by ZETAsizer. It exhibited a controlled drug release profile over a certain period of time, with a slightly increased release and then exhibited a stable profile. Agar well diffusion assay and the LIVE/DEAD BacLight fluorescent assay showed that the formulation had an antibacterial effectiveness against both Bacillus cereus and Staphylococcus aureus . The formulation has a lower minimal inhibitory concentration value against S. aureus . It significantly increased the accumulation of reactive oxygen species in both bacteria when compared with the Amp group. Its cellular uptake and bacterial interaction were confirmed by confocal and transmission electron microscopy images. The in vitro assay revealed that this formulation is nontoxic to fibroblast cells. This study highlights the potential of l ‐glu–Fe ₃ O ₄ –Amp NPs conjugate as a potentially effective antibacterial agent. This is the first report on the use of l ‐glu as a surface modifier of Fe ₃ O ₄ NPs and Amp. Use of l ‐glu increases the drug‐carrying capacity of NPs and reduces the possible side effects of Amp.

Background: Neuroblastoma is the most common extracranial solid malignancy in infants and children. High-risk neuroblastoma patients are commonly treated with temozolomide (TMZ), which typically exhibits a poor therapeutic response. Serotonin, also known as 5-hydroxytryptamine (5-HT), plays various essential functions in the human body. In the central nervous system, it serves as a neurotransmitter. Beyond its physiological roles, 5-HT has recently been identified as a potential growth factor for several human tumors, including gliomas and carcinoid tumors. Recent literature has demonstrated that 5-HT receptor antagonists can inhibit the growth of cancer cells. Furthermore, both 5-HT receptors and their antagonists have been identified as potential anticancer agents, suggesting their significance in the development of new treatment strategies. Objectives: The primary aim of this study was to examine the effects of 5-HT and 5-HT antagonists on tumor (neuroblastoma (SH-SY5Y)) and healthy cells (microglia (HMC3)) and determine the impact of their interaction with the anticancer agent TMZ on cell proliferation/viability and migration. Methods: The study explored the interaction between 5-HT, the 5-HT antagonist granisetron (GRN), the anticancer agent TMZ, and their combinations, specifically assessing their influence on cell proliferation, viability, and migration. Results: As a result, the single and combined applications of 5-HT, TMZ, and GRN, a 5-HT antagonist, inhibited cell growth and proliferation in SH-SY5Y, causing decreased cell viability. Additionally, the combination of 5-HT and GRN increased the efficacy of TMZ. Conclusions: The study findings revealed that 5-HT and 5-HT antagonists may have therapeutic effects by exhibiting antiproliferative effects in SH-SY5Y cells at high concentrations.

Introduction/Objective: Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health. Royal jelly (RJ) is also being studied as a potential therapeutic agent for cancer and other chronic diseases. It is effective in reducing tumor growth and stimulating immunity. Methods: In this study, we investigated the effects of royal jelly on cancerous A549 cells and healthy MRC-5 cells at various doses ranging from 1.25 to 10 mg/mL. Royal jelly's anti-proliferative effect was evaluated by MTT and SRB assay for 48 h. The induction of necrosis and apoptosis was assessed by flow cytometry as well. The relative amounts of major molecules in Royal jelly were determined by FTIR spectroscopy to identify key functional groups and molecular structures. In addition, this technique was used for the first time to detect changes in the macromolecular composition of lung cells treated with royal jelly. Thus, it provided insights into the relative abundance of proteins, lipids, and carbohydrates, which could correlate with their bioactive properties. Results: The antiproliferative effect of Royal jelly was found to be selective on A549 cells in a dose-dependent manner with an IC50 of 9.26 mg/mL, with no cytotoxic effects on normal MRC-5 cells. Moreover, Royal jelly induced predominantly necrotic cell death in A549 cells, %39.10 at 4 mg/ml and %57.88 at 10 mg/ml concentrations. However, the necrosis rate in MRC-5 cells was quite low, at 9.16% and 20.44% at the same doses. Royal jelly showed dose-dependent selective cytotoxicity toward A549 cells, whereas it exhibited no apparent cytotoxicity in MRC-5 cells. In order to identify the biomolecular changes induced by royal jelly, we used two unsupervised chemometric pattern recognition algorithms (PCA and HCA) on the preprocessed sample FTIR spectra to determine the effects of royal jelly on cell biochemistry. According to PCA and HCA results, RJ treatments especially affected biomolecules in A549 cells. The total spectral band variances in the PCA loading spectra were calculated for understanding biomolecular alterations. These plots revealed profound changes in the lipid, protein, and nucleic acid content of RJ-applied lung cells, primarily identifying RJ and H2O2 treated groups for A549 cells. Conclusion: Ultimately, the selective cytotoxicity of royal jelly toward A549 cancerous cells suggests that royal jelly may be a promising therapeutic agent for identifying innovative lung cancer treatment strategies. Additionally, understanding the molecular alterations induced by royal jelly could guide the development of novel cancer treatments that exploit its bioactive properties. This could lead to more effective and safer therapies.

Bisphenol A (BPA) is a substance that can harm the environment and human health by interfering with the normal functioning of the body's hormonal system. It is commonly found in various plastic‐based products such as cosmetics, canned foods, beverage containers, and medical equipment and as well as it can also be absorbed by inhalation. There have been limited studies on the effects of BPA on lung fibroblasts, and it is still unclear how high levels of BPA can impact respiratory system cells, particularly the lungs and trachea. In this research, we aimed to investigate the cell cycle disruption potential of BPA on respiratory system cells by examining healthy trachea and lung cells together for the first time. The findings indicated that BPA exposure can alter the healthy cells' morphology, leading to reduced cellular viability that has been assessed by MTT and SRB assays. BPA treatment was able to activate caspase3 as expected, which could cause apoptosis in treated cells. Although the highest dose of BPA did not increase the apoptotic rate of rat trachea cells, it remarkably caused them to become necrotic (52.12%). In addition to quantifying the induction of apoptosis and necrosis by BPA, cell cycle profiles were also determined using flow cytometry. Thereby, BPA treatment unexpectedly inhibited the cell cycle's progression by causing G2/M cell cycle arrest in both lung and tracheal cells, which hindered cell proliferation. The findings of the study suggested that exposure to BPA could lead to serious respiratory problems, even respiratory tract cancers via alterations in the cell cycle.

Hispidulin çeşitli farmakolojik özelliklere sahip olmasından dolayı uzun süredir kanser araştırmalarında kullanılmaktadır ancak bu maddenin sağlıklı hücrelerde sitotoksik etkisiyle ilgili sınırlı sayıda çalışma bulunmaktadır. Bu çalışmada ilk defa, hispidulin geniş doz aralığında (0-800 μM) sağlıklı hücre hatları ile denendi ve kulanımının güvenliği MTT ve Akım sitometrisi analizleriyle değerlendirildi. Bu amaçla, İnsan akciğer fibroblastı (MRC-5), Sıçan Primer Akciğer Fibroblastı (RA-6013) ve Sıçan Primer Trakeal Fibroblastı (RA-6217) hücreleri 48 saat boyunca hispidulinle muamele edildi. Hispidulin, düşük dozlarda hücre canlılığı üzerinde önemli etkiler göstermedi ancak özellikle 400 ve 800 μM dozlarında hücrelerin canlılığında istatistiksel anlamda ciddi bir azalmaya neden oldu. Hispidulinin IC50 değeri, MRC-5 hücreleri için 563.63 µM, RA-6013 hücrelerinde 194.30 µM ve RA-6217 hücrelerinde ise 311.98 µM olarak belirlendi. Ayrıca 800 μM hispidulin, tüm sağlıklı hücreler üzerinde güçlü apoptotik ve nekrotik etki gösterdi. Sonuçlarımız, hispidulinin düşük dozlarda (0-200 μM) sağlıklı hücrelerde antisitotoksik nitelikte olduğunu ve gelecekteki kanser ve solunum yolu hastalıkları tedavisi için güvenilir doğal bir bileşik olma potansiyeline sahip olduğunu göstermektedir.

This study investigates the protective role of Hispidulin on acute respiratory distress syndrome (ARDS) in rats. Rats were divided into three groups: control, ARDS, ARDS+ Hispidulin. The ARDS models were established by injecting rats with oleic acid. Hispidulin (100 mg/kg) was injected i.p. an hour before ARDS. Myeloperoxidase (MPO), Interleukin-8 (IL-8), Mitogen-activated protein kinases (MAPK), Lipid Peroxidation (LPO), Superoxide Dismutase (SOD), Glutathione (GSH), and Angiotensin-converting enzyme (ACE) were determined by ELISA. Tumor necrosis factor-alpha (TNF-α) expression was described by RT-qPCR. Caspase-3 immunostaining was performed to evaluate apoptosis. Compared with the model group, a significant decrease was observed in the MPO, IL-8, MAPK, ACE, LPO levels, and TNF-α expression in the ARDS+ Hispidulin group. Moreover, reduced caspase-3 immunoreactivity and activity of ACE were detected in the Hispidulin+ARDS group. The protective effect of Hispidulin treatment may act through inhibition of the ACE activity and then regulation of inflammatory cytokine level and alteration of apoptosis.

: Iodine-based contrast agents have limitations such as rapid clearance, potential renal toxicity, non-specific blood pool distribution, headache, and adverse events. Nowadays, it is quite common to work with nanosized systems in order to eliminate the side effects of contrast agents. This study aims to synthesize a new iodinated contrast agent, prepare its nanosuspension by using the nanoprecipitation method, investigate its cytotoxicity, and compare its contrast properties with iohexol and iopromide through in-vitro experiments. The values of nanosuspension particle size and zeta potential have been found to be ~ 400 nm and ~ (-) 15 mV, respectively. In-vitro cellular viability findings indicated that the nanosuspension has lower cytotoxicity than the iohexol and iopromide. In the computed tomography (CT) imaging study of contrast features of nanosuspensions and two commercial agents, which involved 86 CT examinations using 31 parameters and two different devices, it was found that iodine had a stronger presence in its nanosuspension form than in iohexol and iopromide, which were the other two commercial contrast agents, when used in equal amounts. Thus in the case of nanosuspensions contrast brightness was achieved by using less iodine, while the same brightness could be obtained with higher doses of iohexol and iopromide. CT imaging therefore be done without much chemical use, which indicates that it may witness fewer side effects in the future.

Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. The cells were treated with the extracts of I. graveolens (125-1000 μg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

β-blockers having specific affinities to β-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of β-1 selective esmolol, β-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the β-blockers at 150–250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the β-blockers are considered, it seems that β-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.