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51 result(s) for "Duman, Demet"
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Comprehensive Evaluation of Usnic Acid as a Potential Drug Candidate for Triple-Negative Breast Cancer: Insights from Transcriptomic, Proteomic, and In Vivo Analyses
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, prompting extensive research into novel therapeutics. This study presents a comprehensive molecular characterization of usnic acid in TNBC using transcriptomic, proteomic, and in vivo analyses. Results: Transcriptome profiling identified 974 differentially expressed genes (201 upregulated, 773 downregulated; p ≤ 0.05, FC ≥ 2) between control and usnic acid-treated MDA-MB-231 cells, while 4956 DEGs were detected between usnic acid-treated normal epithelial and TNBC cells. Proteomic analysis revealed significant changes in 372 proteins (50 upregulated and 322 downregulated). Functional enrichment analyses indicated that usnic acid modulates key oncogenic pathways, including gonadotropin, CCKR, integrin–ECM signaling, and lipid/energy metabolism. Flow cytometry confirmed increased apoptosis, evidenced by upregulation of pro-apoptotic genes and suppression of anti-apoptotic genes. In vivo xenograft models further validated the tumor-suppressive effects of usnic acid. Conclusions: In light of the findings, this study constitutes the first comprehensive integrated transcriptomic and proteomic evaluation of usnic acid in TNBC, supported by functional and in vivo validation. Collectively, the results position usnic acid as a compelling therapeutic candidate that has successfully passed key in vitro and in vivo preclinical evaluations, warranting further investigation in advanced preclinical models and potential translation toward clinical development for TNBC.
An Approach Appropriate for the Art of Nursing: Individualized Management
Developments in the historical process have made innovation in management approaches inevitable. To adapt to these cultural and managerial changes, new management approaches have emerged at different times. In addition, nursing has undergone many changes in the fields of education, practice, management, and research from the past to the present. The nursing profession has been able to adapt and develop to the needs of the future with what it has learned from experience. In the literature, it is predicted that management approaches will evolve on the basis of information technologies, high ideals, and individual-oriented theories. The concept of individuality in nursing is related to the well-being of nurses who provide health services as well as the results of nursing care that healthy/patient individuals need with their unique qualities. When nurses’ individual experiences, family situations, personality traits, professional knowledge, and experiences are considered in the managerial approach, their contribution to health services and the effectiveness of health care services may increase. This study aimed to explain the concept of individualized management within the framework of the information obtained considering the literature and to make inferences.
Targeting Ferroptosis with Small Molecule Atranorin (ATR) as a Novel Therapeutic Strategy and Providing New Insight into the Treatment of Breast Cancer
Background/Objectives: Ferroptosis results from the accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Previous research has determined the effect of atranorin (ATR) on other cell death mechanisms, but its potential for a ferroptotic effect depending on ROS levels is unclear. This study details the therapeutic role of small-molecule ATR through ferroptosis by suppressing MDA-MB-231, MCF-7, BT-474, and SK-BR-3 breast cancer cells. Methods: The anti-proliferative effect of ATR on cells was evaluated by xCELLigence analysis, and ferroptotic activity was evaluated by enzymatic assay kits. The changes in gene and protein expression levels of ATR were investigated by the qRT-PCR and western blot. In addition, mitochondrial changes were examined by transmission electron microscopy. Results: ATR was found to reduce cell viability in cancer cells in a dose- and time-dependent manner without showing cytotoxic effects on normal breast cells. In BT-474 and MDA-MB-231 cells, ATR, which had a higher anti-proliferative effect, increased iron, lipid peroxidation, and ROS levels in cells and decreased the T-GSH/GSSG ratio. The results revealed for the first time that small-molecule ATR exhibited anti-cancer activity by inducing the glutathione pathway and ferroptosis. Conclusions: This study highlights the potential of ATR as a drug candidate molecule that can be used in the development of new therapeutic strategies for the treatment of triple-negative and luminal-B breast cancer subtypes.
Amphibian Egg Jelly as a Biocompatible Material: Physicochemical Characterization and Selective Cytotoxicity Against Melanoma Cells
Extensive research on amphibians has focused on areas such as morphological and molecular taxonomy, ecology, embryology, and molecular phylogeny. However, the structure and biotechnological potential of egg jelly—which plays a protective and nutritive role for embryos—have remained largely unexplored. This study presents, for the first time, a detailed physicochemical analysis of the egg jelly of Pelophylax ridibundus, an amphibian species, using Fourier Transform Infrared Spectroscopy, Thermogravimetric Analyzer, X-ray Diffraction, and elemental analysis. The carbohydrate content was determined via High-Performance Liquid Chromatography analysis, and the protein content was identified using Liquid Chromatography-Tandem Mass Spectrometry analysis. Additionally, it was revealed that this jelly exhibits a significant cytotoxic effect on melanoma cells (viability < 30%) while showing no cytotoxicity on healthy dermal fibroblast cells (viability > 70%). Consequently, this non-toxic, biologically derived, and cultivable material is proposed as a promising candidate for cancer applications, paving the way for further research in the field.
Helicopter emergency medical services for elderly patients: clinical outcomes and disease patterns
Background The rapid aging of global populations necessitates evidence-based optimization of emergency medical services for elderly patients. This study evaluates helicopter emergency medical services (HEMS) utilization patterns, clinical outcomes, and disease distribution in elderly patients transported to a metropolitan tertiary care facility. Methods Prospective observational study of 119 elderly patients (≥ 65 years) transported via HEMS to Istanbul Başakşehir Çam and Sakura City Hospital between January 2021 and January 2023. Data analysis included disease distribution, transport performance metrics, seasonal variation, and clinical outcomes using descriptive statistics and inferential testing. Results Mean patient age was 74.2 ± 8.4 years. Stroke (30.3%) and cardiovascular conditions (47.1%) represented predominant diagnoses. Mean total transport time was 31.1 min (95% CI: 28.3–33.9). In-hospital mortality was 4.2% (95% CI: 1.4–9.5%), with 28.6% requiring intensive care unit (ICU) admission. Significant seasonal variation occurred ( p  < 0.001, η²=0.42), with 74.8% of cases during spring-summer months. Geographic analysis revealed disparities with 73.1% of patients originating from Çatalca region. Conclusions HEMS represents an essential component of elderly emergency care with favorable clinical outcomes. Age-stratified disease patterns support development of specialized geriatric protocols. Significant seasonal variation and geographic disparities necessitate dynamic resource allocation and policy consideration for equitable HEMS accessibility.
Vulpinic acid as a natural compound inhibits the proliferation of metastatic prostate cancer cells by inducing apoptosis
Background Lichen secondary metabolites have drawn considerable attention in recent years due to the limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. Methods and results After identifying the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effects through G0/G1 arrest, nuclear blebbing and the activation of particularly initiator caspases. Conclusions Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further investigated.
miR-185-5p response to usnic acid suppresses proliferation and regulating apoptosis in breast cancer cell by targeting Bcl2
Background Breast cancer is the most common cancer types among women. Recent researches have focused on determining the efficiency of alternative molecules and miRNAs in breast cancer treatment. The aim of this study was to determine the effect of usnic acid response-miR-185-5p on proliferation in the breast cancer cell and to determine its relationship with apoptosis pathway. Methods The cell proliferation and cell apoptosis rate were significantly increased following the ectopic expression of miR-185-5p in BT-474 cells. Furthermore, the results of cell cycle assay performed by flow cytometry revealed that the transfection with miR-185-5p induced G1/S phase arrest. The apoptosis-related genes expression analysis was performed by qRT-PCR and the direct target of miR-185-5p in BT-474 cells was identified by western blot and luciferase reporter assay. Results Our data showed that miR-185-5p can cause significant changes in apoptosis-related genes expression levels, suggesting that cell proliferation was suppressed by miR-185-5p via inducing apoptosis in breast cancer cells. According to western blot results, miR-185-5p lead to decrease BCL2 protein level in BT-474 cells and direct target of miR-185-5p was identified as BCL by luciferase reporter assay. Conclusion This study revealed that miR-185-5p may be an effective agent in the treatment of breast cancer.
The role of vulpinic acid as a natural compound in the regulation of breast cancer-associated miRNAs
Background Breast cancer is the most frequently diagnosed cancer, and no effective treatment solution has yet been found. The number of studies based on the research of novel natural compounds in the treatment of breast cancer has been increasing in recent years. The anticancer properties of natural compounds are related to the regulation of microRNA (miRNA) expression. Therefore, changing the profile of miRNAs with the use of natural products is very important in cancer treatment. However, the role of vulpinic acid and related miRNAs in breast cancer progression remains unknown. Vulpinic acid, methyl (as2 E )-2-(3-hydroxy-5-oxo-4-phenylfuran-2-ylidene)-2 phenylacetate, is a natural product extracted from the lichen species and shows an anticancer effect on different cancer cells. Methods This study examines the effects of vulpinic acid on the miRNA levels of breast cancer (MCF-7) cells and its relationship with cell proliferation and apoptosis levels. The antiproliferative effect of vulpinic acid was screened against MCF-7 breast cancer cells and MCF-12A breast epithelial cells using the xCELLigence real-time cell analysis system. We analyzed the altered miRNA expression profile in MCF-7 breast cancer cells versus MCF-12A cells following their response to vulpinic acid through microarray analysis. The microarray analysis results were confirmed through quantitative real-time PCR and bioinformatics analysis. Results The results of the miRNA array and bioinformatic analyses demonstrated that 12 miRNAs were specifically responsive to vulpinic acid in MCF-7 breast cancer cells. This is the first study to reveal that vulpinic acid inhibits the expression of 12 miRNAs and suppresses breast cancer cell proliferation. The study also revealed that vulpinic acid may downregulate the expression of 12 miRNAs by repressing the FOXO-3 gene. The miRNA targets were mainly found to play a role in the apoptosis, cell cycle and MAPK pathways. Moreover, Bcl-2, Bax, procaspase-3 and procaspase-9 protein levels were assessed by western blot analysis for validation of apoptosis at the protein level. Conclusion This study revealed the molecular mechanisms of vulpinic acid on breast cancer and showed that vulpinic acid regulates apoptosis signaling pathways by decreasing the expression of miRNAs. The miRNA expression patterns illuminate the underlying effect of vulpinic acid in breast cancer treatment. Graphical Abstract
In silico prediction of type I PKS gene modules in nine lichenized fungi
The novel biologically active molecules could play a significant role in the treatment of human diseases. Natural products have been and continue to be a major source of pharmaceuticals, and lichen secondary metabolites emerge as never-ending potential for bioactive molecules with a variety of pharmacological activities. Polyketides, which are synthesized by enzymes encoded by PKS genes, constitute the major group of these secondary metabolites. To date, there is a lack of information about identification of PKS gene modules. Functional validation studies in lichens are difficult because of the slow growth rates of lichens, the symbiotic partners of lichens cannot be cultured in the laboratory or the fact that most of them cannot be grown in culture. Consequently, the importance of genomic mining approach is increasing as a unique tool for natural product discovery studies. Here, we bioinformatically investigated the type I PKS module candidates in nine publicly available lichen-forming fungi genomes through the use of the in silico screening tools. We also predicted putative secondary metabolites produced in these lichens which indicated the pharmaceutical potential of these nine lichen-forming fungi by bioinformatics tools.
Inducing ferroptosis via nanomaterials: a novel and effective route in cancer therapy
The use of nanomaterials for cancer ferroptosis presents a promising avenue for research and clinical applications. The unique properties of nanomaterials, such as their small size, large surface area, and ability to be engineered for specific tasks, make them ideal candidates for ferroptosis inducing cancer therapies. Ferroptosis is a new type of cell death mechanism that is distinct from apoptosis and necrosis. It has been shown to be critical in the treatment of various tumors. The ferroptotic mechanism has been mainly linked with the regulation of iron, amino acid, glutathione, and lipid metabolism of cells. The relationship between ferroptosis mechanisms and cancer nanomedicine has attracted considerable interest in recent years. It has been reported that the combination of nanomedicine and ferroptosis can achieve high therapeutic efficacy for the treatment of different cancer types. This review will provide an overview of recent work in ferroptosis-related cancer nanomedicine. First, general information is given about the definition of ferroptosis and its differences from other cell death mechanisms. Later, studies exploring the role of ferroptosis in the cancer nanomedicine field are discussed in detail. Specific focus has been given to the use of combinatorial treatment strategies which combine ferroptosis with chemodynamic therapy, photodynamic therapy, photothermal therapy, immunotherapy and sonodynamic therapy. Considering the fact that ferroptosis inducing nanoparticles (NPs) have already been introduced into clinical studies, nanoscientists can further accelerate this clinical translation as they tailor the physicochemical characteristics of nanomaterials. This review provides enlightening information for all researchers interested in the molecular characterization and relationship between ferroptosis and cancer-directed NPs.