Search Results (176)

Background/Objectives: Magnetic iron oxide nanoparticles (IONPs), human serum albumin (HSA) and folic acid (FA) are prospective components for hybrid nanosystems for various biomedical applications. The magnetic nanosystems FA-HSA@IONPs (FAMs) containing IONPs, HSA, and FA residue are engineered in the study. Methods: Composition, stability and integrity of the coating, and peroxidase-like activity of FAMs are characterized using UV/Vis spectrophotometry (colorimetric test using o-phenylenediamine (OPD), Bradford protein assay, etc.), spectrofluorimetry, dynamic light scattering (DLS) and electron magnetic resonance (EMR). The selectivity of the FAMs accumulation in cancer cells is analyzed using flow cytometry and confocal laser scanning microscopy. Results: FAMs (d_N~55 nm by DLS) as a drug delivery platform have been administered to cancer cells (human breast adenocarcinoma MCF-7 and MDA-MB-231 cell lines) in vitro. Methylene blue, as a model photosensitizer, has been non-covalently bound to FAMs. An increase in photoinduced cytotoxicity has been found upon excitation of the photosensitizer bound to the coating of FAMs compared to the single photosensitizer at equivalent concentrations. The suitability of the nanosystems for photodynamic therapy has been confirmed. Conclusions: FAMs are able to effectively enter cells with increased folate receptor expression and thus allow antitumor photosensitizers to be delivered to cells without any loss of their in vitro photodynamic efficiency. Therapeutic and diagnostic applications of FAMs in oncology are discussed. Full article

Background/Objectives: In the context of preclinical studies, we have hitherto showcased that a low-molecular-weight ruthenium(III) complex we named AziRu holds significant potential for further developments as an anticancer candidate drug. When appropriately converted into stable nanomaterials and delivered into tumor cells, AziRu exhibits superior antiproliferative activity, benefiting from a multimodal mechanism of action. The activation of regulated cell death (RCD) pathways (i.e., apoptosis and autophagy) has been proved in metastatic phenotypes, including triple-negative breast cancer (TNBC) cells. This study focuses on a bioengineered lipophilic derivative of AziRu, named PalmiPyRu, that we are currently developing as a potential anticancer drug in preclinical studies. When delivered in this way, AziRu confirms a multimodal mechanism of action in effectively blocking the growth and proliferation of TNBC phenotypes. Special focus is reserved for the activation of the ferroptotic pathway as a consequence of redox imbalance and interference with iron homeostasis, as well as the glutathione biosynthetic pathway. Methods: Human preclinical models of specific TNBC phenotypes and healthy cell cultures of different histological origin were selected. After in vitro treatments, cellular responses were carefully analyzed, and targeted biochemical and molecular biology experiments coupled to confocal microscopy allowed us to explore the antiproliferative effects of PalmiPyRu. Results: In this study, we unveil that PalmiPyRu can enter TNBC cells and interfere with both the iron homeostasis and the cystine-glutamate antiporter system Xc-, causing significant oxidative stress and the accumulation of lipid oxidation products. The increase in intracellular reactive free iron and depletion of glutathione engender a lethal condition, driving cancer cells toward the activation of ferroptosis. Conclusions: Overall, these outcomes allow us, for the first time, to couple the antiproliferative effect of a ruthenium-based candidate drug with the inhibition of the Xc- antiporter system and Fenton chemistry, thereby branding PalmiPyRu as an effective multimodal inducer of ferroptosis. Molecular mechanisms of action deserve further investigations, and new studies are underway to uncover how interference with Xc- controls cell fate, allowing us to explore the connection between iron metabolism regulation, oxidative stress and RCD pathways activation. Full article

Triple-negative breast cancer (TNBC) frequently evades immune recognition and elimination, resulting in an immunosuppressive microenvironment. The phagocytic activity of tumor-associated macrophages underscores the development of nanomaterials as a promising strategy to target these macrophages and modulate their polarization, thereby advancing immunotherapy against TNBC. This research developed functional polymers that are complexed with therapeutic molecules as a coating strategy for iron oxide nanoparticles. An arginine-based poly (ester urea urethane) polymer complexed with a macrophage-polarizing molecule (APU-R848) could provide a synergistic effect with iron oxide nanoparticles (IONPs) to stimulate the M1-polarization of macrophages at the tumor site, resulting in a versatile nano-platform for immune regulation of TNBC. In the 4T1 in vivo breast tumor model, the APU-R848-IONPs demonstrated an improved intratumoral biodistribution compared to IONPs without a polymer coating. APU-R848-IONPs significantly reversed the immune-suppressive tumor environment by reducing the M2/M1 macrophage phenotype ratio by 51%, associated with an elevated population of cytotoxic T cells and a significantly enhanced production of tumoricidal cytokines. The activated immune response induced by APU-R848-IONP resulted in a significant anti-tumor effect, demonstrating an efficacy that was more than 3.2-fold more efficient compared to the controls. These immune-regulatory pseudo-protein-coated iron oxide nanoparticles represent an effective nano-strategy for macrophages’ regulation and the activation of anti-tumor immunity, providing a new treatment modality for triple-negative breast cancer. Full article

Background: Sentinel lymph node biopsy (SLNB) is the primary procedure for nodal assessment in breast cancer patients. Radioisotopes (RIs) are considered the gold-standard tool. The ferromagnetic technique (superparamagnetic iron oxide—SPIO) is a non-isotope alternative SLNB method. This study compares the efficacy of SPIO and RI SLNB across two independent breast cancer centres. Methods: A total of 406 breast cancer patients, who underwent SLNB between January 2021 and December 2022, were analysed (SPIO—223 patients, RI—183 patients). Statistical tests, including Mann–Whitney U and chi-squared analyses, compared the SLN identification rates, the number of SLNs retrieved, and the positive node detection rates. Results: The identification rates were similar for SPIO and RI (two-tailed Fisher’s exact test, p = 1.0). The SPIO method retrieved significantly more SLNs than RI (3.26 vs. 2.15; p < 0.001). A larger proportion of patients in the SPIO group had ≥ 5 SLNs removed (20.2% vs. 8.7%; p = 0.001). A statistically significant difference was observed in the proportion of metastatic SLNs to harvested SLNs between the techniques, with a larger proportion detected in the RI group (1/7.88) compared to the SPIO group (1/14.81) (chi-squared test, p < 0.03). Conclusions: In our study, the SPIO and RI methods effectively collected SLNs. The gold-standard RI method offers distinct advantages, including its precise and consistent dosing unaffected by patient-specific factors and a highly targeted approach to node identification. These features minimise the risk of over-dissection and ensure that only the most clinically relevant nodes are removed. We note that the SPIO technique in SLNB in breast cancer patients requires further standardisation. Full article

Among the distressing side effects of cancer treatments, hair loss is one of the most disturbing for the quality of life and adherence to therapy in breast cancer patients. Many patients take nutritional supplements to prevent hair loss or enhance regrowth. Based on their mechanism and timing of use, nutritional supplements could be divided into safe, cautious, debated, and contraindicated categories. Non-contraindicated supplements generally include safe supplements like vitamin D, which is not known to interfere with cancer treatments. Those that are contraindicated include phytoestrogens and compounds affecting estrogen pathways because of the risk of stimulating tumor growth in cancers sensitive to estrogen. Antioxidants like tocotrienols and resveratrol are given judiciously because of potential interference with cancer therapies dependent on reactive oxygen species. Supplements debated, including nicotinamide, folate, and iron, pose a risk by promoting cellular proliferation or altering the tumor microenvironment. Biotin is nontoxic but interferes with blood test results and is thus difficult in cancer monitoring. Evidence regarding nutritional supplements’ safety and efficacy in this context is conflicting. Management by an oncologist is required along with more studies to clearly establish the safety parameters and efficacy guidelines. Full article

Background: More and more women are following a vegan and vegetarian diet. For some, the use of a vegan diet during lactation is controversial. Purpose: The aim of the study was to comparatively analyze the concentration of selected hormones, micro- and macronutrients, vitamins, and the basic composition and antioxidant status of the milk of vegan women, compared to the milk of omnivorous women. Methods: The study included 17 breastfeeding vegan women and 27 omnivorous women. The basic composition of human milk was analyzed using the MIRIS HMATM analyzer (Uppsala, Sweden) The levels of hormones and vitamins were determined by the enzyme-linked immunosorbent method. In order to determine the antioxidant activity and micro- and macroelements, spectrophotometric methods were used. Results: The vegan group was characterized by a lower average age, lower BMI, and lower WHR index compared to the control group. The milk of vegan women showed significantly higher cortisol concentrations and lower iron, vitamin B6, and antioxidant status than the milk of omnivorous women. Conclusions: A vegan diet helps maintain a healthy body weight and is more popular among younger women, under 30 years of age. Higher levels of milk cortisol in vegan women may indicate a high level of anxiety and stress experienced by breastfeeding women, which may have negative consequences not only for breastfeeding mothers but also for the development of their children. Lack of appropriate supplementation in women who do not consume meat and animal products may cause a deficiency of micro- and macroelements in breast milk. Full article

Background/Objectives: Cancer cells often display altered energy metabolism. In particular, expression levels and activity of the tricarboxylic acid cycle (TCA cycle) enzymes may change in cancer, and dysregulation of the TCA cycle is a frequent hallmark of cancer cell metabolism. MEMO1, a modulator of cancer metastasis, has been shown to bind iron and regulate iron homeostasis in the cells. MEMO1 knockout changed mitochondrial morphology and iron content in breast cancer cells. Our previous genome-wide analysis of MEMO1 genetic interactions across multiple cancer cell lines revealed that gene sets involved in mitochondrial respiration and the TCA cycle are enriched among the gain-of-function interaction partners of MEMO1. Based on these findings, we measured the TCA cycle metabolite levels in breast cancer cells with varying levels of MEMO1 expression. Methods: ShRNA knockdown assay was performed to test essentiality of key TCA cycle enzymes. TCA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in MDA-MB-231 (high MEMO1), M67-2 (MEMO1 knockdown), and M67-9 (MEMO1 knockout) cells under iron-depleted, basal iron, and iron-supplemented conditions. Results:ACO2 and OGDH knockdowns inhibit cell proliferation, indicating an essential role of the TCA cycle in MDA-MB-231 metabolism. α-Ketoglutarate and citrate levels exhibited an inverse relationship with MEMO1 expression, increasing significantly in MEMO1 knockout cells regardless of iron availability. In contrast, fumarate, malate, and glutamate levels were elevated in MEMO1 knockout cells specifically under low iron conditions, suggesting an iron-dependent effect. Conclusions: Overall, our results indicate that MEMO1 plays a role in regulating the TCA in cancer cells in an iron-dependent manner. Full article

Doxorubicin (DOX) is used for the treatment of various malignancies, including leukemias, lymphomas, sarcomas, and bladder, breast, and gynecological cancers in adults, adolescents, and children. However, DOX causes severe side effects in patients, such as cardiotoxicity, which encompasses heart failure, arrhythmia, and myocardial infarction. DOX-induced cardiotoxicity (DIC) is based on the combination of nuclear-mediated cardiomyocyte death and mitochondrial-mediated death. Oxidative stress, altered autophagy, inflammation, and apoptosis/ferroptosis represent the main pathogenetic mechanisms responsible for DIC. In addition, in vitro and in vivo models of DIC sirtuins (SIRT), and especially, SIRT 1 are reduced, and this event contributes to cardiac damage. In fact, SIRT 1 inhibits reactive oxygen species and NF-kB activation, thus improving myocardial oxidative stress and cardiac remodeling. Therefore, the recovery of SIRT 1 during DIC may represent a therapeutic strategy to limit DIC progression. Natural products, i.e., polyphenols, as well as nano formulations of DOX and iron chelators, are other potential compounds experimented with in models of DIC. At present, few clinical trials are available to confirm the efficacy of these products in DIC. The aim of this review is the description of the pathophysiology of DIC as well as potential drug targets to alleviate DIC. Full article

Nanotechnology has revolutionized cancer therapy by enabling targeted drug delivery and overcoming limitations associated with conventional chemotherapy. In this study, we explored the anticancer potential of gold–iron oxide (Au-Fe₃O₄@PEG) nanourchins (NUs), a class of nanoparticles with unique shape, surface features, and plasmonic properties. We tested NUs on several cancer cell lines, including A375 (melanoma), MCF7 (breast), A549 (lung), and MIA PaCa-2 (pancreatic), and observed significant dose-dependent cytotoxicity, with A549 cells exhibiting the highest resistance. Our findings also demonstrate that NUs induce oxidative stress, disrupt mitochondrial function, and activate autophagic and paraptotic cell death pathways in A549 lung cancer cells. Additionally, we explored the potential of NUs to enhance the efficacy of platinum-based chemotherapy, specifically cisplatin, in A549. The results provide valuable insights into the therapeutic potential of NUs in the context of cancer treatment, particularly for overcoming drug resistance and enhancing the effectiveness of conventional chemotherapy. Full article

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited effective treatments available, including targeted therapies, often leading to poor prognosis. Mitotic checkpoint kinase BUB1 is frequently overexpressed in TNBC and correlates with poor survival outcomes suggesting its potential as a therapeutic target. This study explores the cytotoxicity of TNBC cells to BUB1 inhibition, alone or in combination with radiation and demonstrates that ferroptosis, an iron-dependent form of programmed cell death, has a role. Methods: TNBC cell lines (SUM159, MDA-MB-231, and BT-549) were treated with a BUB1 inhibitor BAY1816032 (BUB1i) alone or in combination with the ferroptosis activator RSL3 with or without 4 Gy irradiation. Cell viability assays were conducted to assess treatment effects, qPCR analyses measured expression of key ferroptosis markers including ACSL4, GPX4, PTGS2, SLC7A11, NCOA4, IREB2, NFS1, and TFRC expression, and TBARS assay measured the lipid peroxidation levels. Ferroptosis specificity was confirmed through co-treatment with the ferroptosis inhibitor Ferrostatin-1 (F-1). Results: In all TNBC cell lines studied, BUB1 inhibition significantly induced ferroptosis, marked by increased expression of ACSL4 and PTGS2, decreased expression of GPX4 and SLC7A11, and increased lipid peroxidation levels. The combination of BUB1i with RSL3 further amplified these ferroptotic markers, suggesting at least an additive effect, which was not present with the combination of BUB1i and radiation. Co-treatment with Ferrostatin-1 reversed the expression of ferroptosis markers, suggesting that BUB1i-mediated cell death may involve ferroptotic signaling in TNBC cell lines. Conclusions: This study demonstrates that BUB1 inhibition may independently induce ferroptosis in TNBC cell lines, which is enhanced when combined with a ferroptosis activator. Further research is warranted to delineate the molecular mechanism of BUB1-mediated ferroptosis in TNBC. Full article

Triple-negative breast cancer (TNBC) presents limited therapeutic options and is characterized by a poor prognosis. Although Kinsenoside (KIN) possesses a wide range of pharmacological activities, its effect and mechanism in TNBC remain unclear. The objective of this research was to explore the therapeutic effectiveness and the molecular mechanisms of KIN on TNBC. Xenograft experiment was carried out to assess the impact of KIN on TNBC in vivo. The effect of KIN on TNBC in vitro was evaluated through the analysis of cell cytotoxicity and colony formation assays. Oil Red O staining and BODIPY 493/503 fluorescence staining were employed to detect the effect of KIN on lipid droplet (LD) formation. Transcriptomics and inhibitor-rescue experiments were conducted to investigate the role of KIN on TNBC. Mechanistic experiments, including quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, diacylglycerol acyltransferase 1 (DGAT1) overexpression assay, and flow cytometric assay, were employed to uncover the regulatory mechanisms of KIN on TNBC. KIN inhibited tumor growth without causing obvious toxicity to the liver and kidneys. In vitro experiments demonstrated that KIN significantly inhibited the viability and proliferation of TNBC cells, accompanied by decreased LD formation and lipid content. Polyunsaturated fatty acids (PUFAs) levels were significantly increased by KIN. Furthermore, transcriptomics and inhibitor-rescue experiments revealed that KIN induced ferroptosis in TNBC cells. KIN could significantly regulate ferroptosis-related proteins. Lipid peroxidation, iron accumulation, and GSH depletion also confirmed this. The LD inducer mitigated the KIN-induced ferroptosis in TNBC. The overexpression of DGAT1 attenuated the effects of KIN on cell viability and proliferation. Furthermore, the overexpression of DGAT1 inhibited the effect of KIN to trigger ferroptosis in TNBC cells. Our findings confirmed that KIN could trigger ferroptosis by suppressing DGAT1-mediated LD formation, thereby demonstrating a promising therapeutic effect of KIN in TNBC. Full article

Background/Objectives: Ferroptosis, a type of programmed cell death, is mainly associated with disruptions in iron metabolism, imbalances in the amino acid antioxidant system, and the build-up of lipid peroxides. Triple-negative breast cancer (TNBC) has a dismal prognosis. Since activating ferroptosis can suppress breast cancer cell proliferation, it holds promise as a novel therapeutic target for breast cancer patients. Thus, the objective of this study was to clarify the mechanism of ferroptosis in TNBC, aiming to find new treatment strategies for TNBC patients. Methods: We screened out the differential genes related to ferroptosis in TNBC after GluOC treatment based on the whole-genome sequencing results. At the cellular level, we conducted explorations using techniques such as quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, fluorescence staining, and siRNA transfection. Moreover, we further verified the role of GluOC in inhibiting ferroptosis in TNBC through in vivo experiments using nude mice. Results: The results showed that GluOC enhanced glutathione expression levels by inducing SLC7A11 accumulation via the specific signaling pathway. Additionally, GluOC increased ATP production and tricarboxylic acid flux resistance to ferroptosis through SLC38A1. Overall, GluOC coordinately regulated SLC7A11 and SLC38A1 to inhibit ferroptosis in TNBC. Conclusions: This study elucidated the mechanism of GluOC in inhibiting ferroptosis in TNBC. The findings not only provided new insights into ferroptosis but also potentially offered new concepts for the development of future anticancer therapies, which may contribute to improving the treatment of TNBC patients. Full article

This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but also provide insights into the factors driving predictions, addressing the need for trustworthy AI in healthcare. Several classification models were evaluated, including OneR, JRIP, the FURIA, J48, the ADTree, and the Random Forest, all of which are known for their explainability. The dataset included a variety of biomarkers, such as electrolytes, metal ions, marker proteins, enzymes, lipid profiles, peptide hormones, steroid hormones, and hormone receptors. The Random Forest model achieved the highest accuracy at 99.401%, followed closely by JRIP, the FURIA, and the ADTree at 98.802%. OneR and J48 achieved 98.204% accuracy. Notably, the models identified oxytocin as a key predictive biomarker, with most models featuring it in their rules. Other significant parameters included GnRH, $\beta$-endorphin, vasopressin, IRAP, and APB, as well as factors like iron, cholinesterase, the total protein, progesterone, 5-nucleotidase, and the BMI, which are considered clinically relevant to breast cancer pathogenesis. This study discusses the roles of the identified parameters in cancer development, thus underscoring the potential of explainable machine learning models for enhancing early breast cancer diagnosis by focusing on explainability and the use of serum biomarkers.The combination of both can lead to improved early detection and personalized treatments, emphasizing the potential of these methods in clinical settings. The identified markers also provide additional research and therapeutic targets for breast cancer pathogenesis and a deep understanding of their interactions, advancing personalized approaches to breast cancer management. Full article

One of the most significant industries in the world is the meat sector, and development into new goods is ongoing due to high customer demand and fierce market competition. Products made from chicken are widely favored. This phenomenon can be attributed to the lack of cultural or religious restrictions on this meat. The study looks into how using two distinct types of iron-rich fillings impacts the sensory profile of classic chicken roulades. The purpose of the study is to determine how changes in sensory qualities (such as taste, texture, and flavor) affect product acceptance among customers. This approach uses methods like check-all-that-apply (CATA), principal component analysis (PCA), external preference mapping (PrefMap), and penalty analysis to explore the impact of adding chicken offals and spinach as fillings on the sensory profile of traditional chicken meat roulades. This approach seeks to expand the meat product category, create new goods that use both plant and animal components, invent new ways to use offals and spinach in the market, and ensure that consumers accept these new products. Based on the results of our investigation, the type of filling utilized in the roulades showed the most differences across all sensory tests. According to hedonic analysis and preference mapping (PrefMap), the majority of customers favored roulades with spinach fillings as opposed to those containing chicken offals, which only a small portion of customers liked. Variations in consumer preference for roulades filled with chicken offals were noted in the anatomical region, with slightly greater preference for roulades made from chicken breast. However, this (anatomical region used) did not significantly affect the outcomes of all sensory tests. The spinach stuffing was found to be quite popular with the customers, even outperforming traditional chicken roulades, making it the most significant influence. Based on consumer appreciation, this suggests that the spinach-filled chicken roulades may be a viable option for meat products in the future. Full article

Due to their intriguing emission profile, Terbium-161 (¹⁶¹Tb) radiopharmaceuticals seem to bring significant advancement in theranostic applications to cancer treatment. The combination of ¹⁶¹Tb with nanoscale brachytherapy as an approach for cancer treatment is particularly advantageous and promising. Herein, we propose the application of a hybrid nanosystem comprising gold decorated (Au@TADOTAGA) iron oxide nanoflowers as a form of injectable nanobrachytherapy for the local treatment of breast cancer. More specifically, Au@TADOTAGA and NFAu@TADOTAGA NPs were efficiently radiolabeled with ¹⁶¹Tb, and their in vitro stability was assessed up to 21 d post-radiolabeling. Furthermore, their cytotoxic profile against 4T1 breast cancer cells was evaluated, and their ex vivo biodistribution characteristics were revealed after intratumoral injection in the same animal model. The enhanced retention at the tumor site urged us to evaluate the therapeutic effect of the [¹⁶¹Tb]Tb-NFAu@TADOTAGA nanosystem after intratumoral administration to 4T1-tumor-bearing mice, over a period of 24 days. Three different therapeutic protocols were performed in order to identify which therapeutic approach would offer the optimum results and identify the proposed nanosystem as a promising nanoscale brachytherapy agent. Full article