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1.
J Gambl Stud ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805161

ABSTRACT

The aim of this study is to examine the relationship between gambling behavior, self-confidence, and psychological resilience levels among university students. Additionally, the study aims to investigate the relationship between gambling behavior and socio-demographic variables. This descriptive and cross-sectional study was conducted between April and June 2023. The research employed a questionnaire, the Brief Psychological Resilience Scale, the South Oaks Gambling Screen (SOGS), and the Self-Confidence Scale. The study was carried out online, reaching 229 students through Google Forms. According to the SOGS scores, 4.8% of the students are at risk of gambling addiction. Male students have statistically significantly higher SOGS scores than female students. The SOGS score is significantly higher in working students, smokers, and alcohol drinkers (p < 0.05). No statistically significant relationship was found between the students' SOGS scores and the self- confidence scale (p = 0.637) and the brief resilience scale (p = 0.675). It is thought that training should be given to risky groups in order to prevent gambling behavior. In addition, it is thought that supporting university students to be active in different arts and sports fields may have a positive effect on preventing and reducing addictions.

2.
Breast Cancer Res ; 26(1): 87, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816770

ABSTRACT

BACKGROUND: Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis. METHODS: To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively. RESULTS: Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo. CONCLUSIONS: Reduced metastasis upon silencing supports EDI3's potential as a treatment target in metastasizing ER-HER2+ breast cancer.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Receptors, Estrogen , Animals , Female , Humans , Mice , Cell Line, Tumor , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Receptors, Estrogen/metabolism , Disease Models, Animal , Cell Movement , Gene Knockdown Techniques , Tumor Burden , Neoplasm Metastasis , Lung Neoplasms/secondary , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Cell Proliferation
3.
J Exp Clin Cancer Res ; 42(1): 25, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36670508

ABSTRACT

BACKGROUND: Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored. METHODS: EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo. RESULTS: In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3ß, and transcription factors, including HIF1α, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo. CONCLUSIONS: Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Phosphatidylinositol 3-Kinases , Cell Line, Tumor , Choline/metabolism , Choline/therapeutic use , RNA, Small Interfering , Receptor, ErbB-2/metabolism , Drug Resistance, Neoplasm/genetics , Phospholipases/genetics
4.
Mol Divers ; 27(6): 2767-2787, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36508118

ABSTRACT

Herein, we present how to synthesize thirteen new 1-(4-acetylphenyl)-3-alkylimidazolium salts by reacting 4-(1-H-imidazol-1-yl)acetophenone with a variety of benzyl halides that contain either electron-donating or electron-withdrawing groups. The structures of the new imidazolium salts were conformed using different spectroscopic methods (1H NMR, 13C NMR, 19F NMR, and FTIR) and elemental analysis techniques. Furthermore, these compounds' the carbonic anhydrase (hCAs) and acetylcholinesterase (AChE) enzyme inhibition activities were investigated. They showed a highly potent inhibition effect toward AChE and hCAs with Ki values in the range of 8.30 ± 1.71 to 120.77 ± 8.61 nM for AChE, 16.97 ± 2.04 to 84.45 ± 13.78 nM for hCA I, and 14.09 ± 2.99 to 69.33 ± 17.35 nM for hCA II, respectively. Most of the synthesized imidazolium salts appeared to be more potent than the standard inhibitor of tacrine (TAC) against AChE and Acetazolamide (AZA) against CA. In the meantime, to prospect for potential synthesized imidazolium salt inhibitor(s) against AChE and hCAs, molecular docking and an ADMET-based approach were exerted.


Subject(s)
Cholinesterase Inhibitors , Salts , Salts/pharmacology , Cholinesterase Inhibitors/chemistry , Acetylcholinesterase/metabolism , Carbonic Anhydrase I/chemistry , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase II/chemistry , Carbonic Anhydrase II/metabolism , Molecular Docking Simulation , Structure-Activity Relationship , Molecular Structure
5.
Arch Pharm (Weinheim) ; 354(5): e2000422, 2021 May.
Article in English | MEDLINE | ID: mdl-33427318

ABSTRACT

Chloro-/fluorobenzyl-substituted benzimidazolium salts were synthesized from the reaction of 4-fluorobenzyl/2-chloro-4-fluorobenzyl-substituted benzimidazole and chlorinated aromatic hydrocarbons. They were characterized using various spectroscopic techniques (Fourier-transform infrared and nuclear magnetic resonance) and elemental analysis. In addition, the crystal structures of the complexes 1a -d and 2b were determined by single-crystal X-ray diffraction methods. These compounds were crystallized in the triclinic crystal system with a P-1 space group. The crystal packing of all complexes is dominated by O-H⋯Cl hydrogen bonds, which link the water molecules and chloride anions, forming a chloride-water tetrameric cluster. These synthesized salts were found to be effective inhibitors for α-glycosidase and acetylcholinesterase (AChE), with Ki values ranging from 45.77 ± 6.83 to 102.61 ± 11.56 µM for α-glycosidase and 0.94 ± 0.14 to 10.24 ± 1.58 µM for AChE. AChE converts acetylcholine into choline and acetic acid, thus causing the return of a cholinergic neuron to its resting state. Discovering AChE and α-glycosidase inhibitors is one of the important ways to develop new drugs for the treatment of Alzheimer's disease and diabetes.


Subject(s)
Benzimidazoles/pharmacology , Cholinesterase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Acetylcholinesterase/metabolism , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Glycoside Hydrolase Inhibitors/chemical synthesis , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolases/metabolism , Humans , Models, Molecular , Molecular Structure , Salts/chemical synthesis , Salts/chemistry , Salts/pharmacology , Structure-Activity Relationship
6.
Ecotoxicol Environ Saf ; 147: 749-758, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28942278

ABSTRACT

Studies addressing the toxicity of pesticides towards non-target organisms focus on the median lethal concentration and biochemical response of individual pesticides. However, when determining environmental risks, it is important to test the combined effects of pesticides, such as insecticides and herbicides, which are frequently used together in agricultural areas. Here we aimed to investigate the toxic effects of the combined use of the herbicide atrazine and the insecticides, endosulfan, indoxacarb, and thiamethoxam on Gammarus kischineffensis. To do this, we tested the activities of oxidative stress, detoxification, and neurotoxicity biomarkers. Compared to atrazine alone, we detected higher glutathione-S-transferase, catalase and superoxide dismutase activities (oxidative stress biomarkers) when atrazine was combined with either endosulfan or indoxacarb. However, higher IBR values were determined in organisms where pesticide mixtures were used according to individual use. Based on these results, mixtures of atrazine and other pesticides may cause synergistic effects and may be evidence of increased toxicity and oxidative stress.


Subject(s)
Amphipoda/drug effects , Environmental Monitoring/methods , Herbicides/toxicity , Insecticides/toxicity , Soil Pollutants/toxicity , Amphipoda/enzymology , Animals , Atrazine/toxicity , Biomarkers/analysis , Dose-Response Relationship, Drug , Drug Synergism , Endosulfan/toxicity , Lethal Dose 50 , Neonicotinoids/toxicity , Nitro Compounds/toxicity , Oxazines/toxicity , Oxidative Stress/drug effects , Thiamethoxam , Thiazoles/toxicity , Time Factors , Toxicity Tests, Acute
7.
Cell Biochem Funct ; 31(1): 86-90, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22886507

ABSTRACT

Interest in environmental-pollutant-induced oxidative stress and knowledge of the interactions between reactive oxygen species and cellular systems have increased in toxicology and microbial ecology considerably in recent decades. These reactive oxidants are produced by a variety of environmental sources: ionizing radiations, ultraviolet light, redox cycling drugs, hyperoxia, ischemia and redox-active xenobiotics or during metabolism of environmental pollutants, such as heavy metals in mining industries, dyes in wastewater of textile industries, pesticides and polycyclic hydrocarbons, i.e. foreign materials. In this study, the effect of dye on the antioxidative defence system of Phanerochaete chrysosporium was investigated, and we showed the ability of Phanerochaete chrysosporium to antioxidative response and defence system exposed to Astrazone Red FBL. Catalase, glutathione reductase, glutathione s-transferase activities and level of glutathione decreased, depending on the period of growth in each exposure to low and high concentration group (20 and 50 ppm) compared with the control group.


Subject(s)
Azo Compounds/toxicity , Coloring Agents/toxicity , Phanerochaete/drug effects , Water Pollutants, Chemical/toxicity , Azo Compounds/administration & dosage , Biodegradation, Environmental , Catalase/metabolism , Coloring Agents/administration & dosage , Dose-Response Relationship, Drug , Fungal Proteins/metabolism , Glutathione/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Oxidation-Reduction , Oxidative Stress/drug effects , Phanerochaete/enzymology , Phanerochaete/growth & development , Water Pollutants, Chemical/administration & dosage
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