Search Results (4,231)

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

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

The C-kinase-activated protein phosphatase-1 (PP1) inhibitor of 17 kDa (CPI-17) is a specific inhibitor of the PP1 catalytic subunit (PP1c) and the myosin phosphatase (MP) holoenzyme. CPI-17 requires the phosphorylation of Thr38 in the peptide segment ³⁵ARV(P)TVKYDRREL⁴⁶ for inhibitory activity. CPI-17 regulates myosin phosphorylation in smooth muscle contraction and the tumorigenic transformation of several cell lines via the inhibition of MP. A phosphospecific antibody (anti-CPI-17^pThr38) against the phosphorylation peptide was used to determine the phosphorylation levels in cells. We found that phospho-CPI-17 and its closely related proteins are not present in HeLa and MCF7 cells after inducing phosphorylation by inhibiting phosphatases with calyculin A. In contrast, cross-reactions of proteins in the 40–220 kDa range with anti-CPI-17^pThr38 were apparent. Searching the protein database for similarities to the CPI-17 phosphorylation sequence revealed several proteins with 42–75% sequence identities. The LIMK2-1 isoform emerged as a possible PP1 inhibitor. Experiments with Flag-LIMK2-1 overexpressed in tsA201 cells proved that LIMK2-1 interacts with PP1c isoforms and is phosphorylated predominantly by protein kinase C. Phosphorylated LIMK2-1 inhibits PP1c and the MP holoenzyme with similar potencies (IC50 ~28–47 nM). In conclusion, our results suggest that LIMK2-1 is a novel phosphorylation-dependent inhibitor of PP1c and MP and may function as a CPI-17-like phosphatase inhibitor in cells where CPI-17 is present but not phosphorylated upon phosphatase inhibition. Full article

Due to its lightweight and superior adsorption properties, carbon foam is frequently employed for the removal of heavy metal pollutants from aqueous solutions. In this study, a novel modified carbon foam (M-CF) was successfully synthesized for the effective removal of Pb²⁺ and Cd²⁺ from water. The synthesis involved partially substituting phenol with the liquefaction product of bamboo powder, followed by modification with a silane coupling agent (KH560) and foaming with n-hexane-loaded activated carbon (H/AC). The prepared carbon foam was comprehensively characterized, and its adsorption performance and mechanism for Pb²⁺ and Cd²⁺ in aqueous solution were investigated. The results showed that M-CF possessed a uniform and well-developed spherical pore structure and demonstrated excellent removal capacity for Cd²⁺ and Pb²⁺. The adsorption process conformed to the Sips isotherm model and the pseudo-second-order kinetic equation, with maximum adsorption capacities of 22.15 mg·g⁻¹ and 61.59 mg·g⁻¹ for Cd²⁺ and Pb²⁺, respectively. Mechanistic analysis revealed that the removal of Cd²⁺ and Pb²⁺ was a result of the synergistic effect of physisorption and chemisorption, accompanied by complexation. Furthermore, precipitates formed during the adsorption process were found to be mainly composed of hydroxides, carbonates, and PbS. This research demonstrates the efficacy of carbon foam prepared from bamboo powder waste as a partial phenol substitute for the efficient removal of Pb²⁺ and Cd²⁺ from water, thus expanding the preparation pathways for novel heavy metal adsorption materials. Full article

This study investigates the effects of copper nanoparticles (CuNPs) on KRT19 gene expression in four breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF7, and T47D), representing triple-negative and luminal subtypes. Using cytotoxicity assays, quantitative RT-PCR, and bioinformatics tools (STRING, g:Profiler), we demonstrate subtype-specific, dose-dependent KRT19 suppression, with epithelial-like cell lines showing greater sensitivity. CuNPs, characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM) with a mean size of 179 ± 15 nm, exhibited dose-dependent cytotoxicity. Bioinformatics analyses suggest KRT19′s potential as a biomarker for CuNP-based therapies, pending in vivo and clinical validation. These findings highlight CuNPs’ therapeutic potential and the need for further studies to optimize their application in personalized breast cancer treatment. Full article

The increasing prevalence of cancer necessitates the development of novel and effective therapeutic agents. This study evaluates the anticancer potential of biosynthesized copper oxide nanoparticles (CuO NPs) using Camellia sinensis extract against human colon and breast cancer cells. The CuO NPs were characterized using various techniques to confirm their structure, size, morphology, and functional groups. The average size of CuO NPs synthesized was 20–60 nm, with spherical shape. The cytotoxic effects of these CuO NPs reveal a dose-dependent reduction in cell viability with 50% inhibitory concentration (IC₅₀) at 58.53 ± 0.13 and 53.95 ± 1.1 μg/mL, respectively. Further investigation into the mechanism of action was conducted using flow cytometry and apoptosis assays, which indicated that CuO NPs induced cell cycle arrest and apoptosis in cancer cells. Reactive oxygen species (ROS) generation, caspase activity assay, and comet assay were also performed to elucidate the underlying pathways, suggesting that oxidative stress and DNA damage play pivotal roles in the cytotoxicity observed. Overall, our findings demonstrate that biosynthesized CuO NPs exhibit notable anticancer activity against colon and breast cancer cells, with moderate selectivity over normal cells, highlighting their potential as a therapeutic agent due to their biocompatibility. However, further studies are required to validate their selectivity and safety profile. Full article

The synthesis of 2-phenylbenzoxazole fluorosulfate derivatives was carried out using the SuFEx reaction. To study the anticancer properties of the obtained compounds, the cell lines PC-3 (obtained from prostate adenocarcinoma), BT-474, and MCF-7 (both obtained from breast carcinoma) were used. The cytotoxicity on murine 3T3L1 embryonic was also investigated. Among the tested compounds, the ortho-substituted fluorosulfate derivative (BOSo) exhibited significant cytotoxicity against MCF-7 cells. The biological findings are consistent with molecular docking results, which revealed a structural similarity between BOSo and known inhibitors of hER and HER2 receptors—tamoxifen and SYR127063. Therefore, BOSo shows promise as a potential therapeutic agent with antiproliferative properties. The photoluminescent characteristics of the fluorosulfate derivatives were examined in the solid state, in acetonitrile solution and in PBS, with the highest quantum yields reaching up to 64% for the para-fluorosulfate derivative in acetonitrile. Overall, these compounds demonstrate considerable potential for the development of new multifunctional molecular tools that combine biological activity with fluorescent properties. Full article

This study explores the valorization of agro-industrial by-products—riceberry broken rice (RBR) and soybean meal (SBM)—as cost-effective substrates for enhancing exopolysaccharide (EPS) production by Bacillus tequilensis PS21. Eight Bacillus strains were screened, and B. tequilensis PS21 demonstrated the highest EPS yield (2.54 g/100 mL DW). The EPS displayed a strong antioxidant capacity with 65.5% DPPH and 80.5% hydroxyl radical scavenging, and a FRAP value of 6.51 mg Fe²⁺/g DW. Antimicrobial testing showed inhibition zones up to 10.07 mm against Streptococcus agalactiae and 7.83 mm against Staphylococcus aureus. Optimization using central composite design (CCD) and the response surface methodology (RSM) revealed the best production at 5% (w/v) RBR, 3% (w/v) SBM, pH 6.66, and 39.51 °C, yielding 39.82 g/L EPS. This EPS is a moderate-molecular-weight (11,282 Da) homopolysaccharide with glucose monomers. X-ray diffraction (XRD) showed an amorphous pattern, favorable for solubility in biological applications. Thermogravimetric analysis (TGA) demonstrated thermal stability up to ~250 °C, supporting its suitability for high-temperature processing. EPS also exhibited anticancer activity with IC₅₀ values of 226.60 µg/mL (MCF-7) and 224.30 µg/mL (HeLa) at 72 h, reduced colony formation, inhibited cell migration, and demonstrated anti-tyrosinase, anti-collagenase, and anti-elastase effects. This study demonstrates the successful valorization of agro-industrial by-products—RBR and SBM—for the high-yield production of multifunctional EPS with potent antioxidant, antimicrobial, and anticancer properties. The findings highlight the sustainable potential of these low-cost substrates in supporting the development of green and value-added bioproducts, with promising utilizations across the food, pharmaceutical, and cosmetic sectors. Full article

Chloroplasts, as the organelles primarily responsible for photosynthesis, require a substantial supply of iron ions. Conversely, due to Fe toxicity, the homeostasis of these ions is subject to tight regulation. Permease in chloroplast 1 (PIC1) has been identified as the primary iron importer into chloroplasts. However, previous studies suggested the existence of a distinct pathway for Fe transfer to chloroplasts, likely involving mitoferrin-like 1 (MFL1) protein. In this work, Arabidopsis MFL1 (AtMFL1) and its cucumber homolog (CsMFL1) were characterized using, among others, Arabidopsis protoplasts as well as both yeast and Arabidopsis mutants. Localization of both proteins in chloroplasts has been shown to be mediated via an N-terminal transit peptide. At the gene level, MFL1 expression profiles differed between the model plant and the crop plant under varying Fe availability. The expression of other genes involved in chloroplast Fe homeostasis, including iron acquisition, trafficking, and storage, was affected to some extent in both AtMFL1 knockout and overexpressing plants. Moreover, root growth and photosynthetic parameters changed unfavorably in the mutant lines. The obtained results imply that AtMFL1 and CsMFL1, as putative chloroplast iron transporters, play a role in both iron management and the proper functioning of the plant. Full article

Origanum majorana L. (O. majorana) (Lamiaceae) is an aromatic Mediterranean plant widely used in food, cosmetics, and traditional medicine due to its aroma and rich content of bioactive compounds. While its leaves and flowers are commonly utilized, lignified stems are often discarded. This study compared hydroalcoholic extracts from the leaves and flowers (valuable fraction, VF) and stems (by-product, BP). Phytochemical analysis revealed qualitatively similar profiles, identifying 20 phenolic compounds, with Rosmarinic acid and Salvianolic acid B as the most and second most abundant, respectively. Antioxidant activity was evaluated in vitro using DPPH (IC₅₀ [µg/mL]: VF 30.11 ± 3.46; BP 31.72 ± 1.46), H₂O₂ (IC₅₀ [µg/mL]: VF 103.09 ± 4.97; BP 119.55 ± 10.58), and O₂^•− (IC₅₀ [µg/mL]: VF 0.71 ± 0.062; BP 0.79 ± 0.070). Both extracts (20 µg/mL) fully restored oxidative balance in hemin-stressed AC16 cardiomyocytes, without altering the expression of catalase, heme-oxygenase 1, superoxide dismutase 2, or ferritin. Anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages showed that VF (IC₅₀ 400 µg/mL) reduced ^•NO release to control levels, while BP achieved a ~60% reduction. Cytotoxicity was assessed on cancer cell lines: CaCo-2 (IC₅₀ [µg/mL]: VF 154.1 ± 6.22; BP 305.2 ± 15.94), MCF-7 (IC₅₀ [µg/mL]: VF 624.6 ± 10.27; BP 917.9 ± 9.87), and A549 (IC₅₀ [µg/mL]: VF 720.8 ± 13.66; BP 920.2 ± 16.79), with no cytotoxicity on normal fibroblasts HFF-1 (IC₅₀ > 1000 µg/mL for both extracts). Finally, both extracts slightly inhibited only CYP1A2 (IC₅₀ [µg/mL]: VF 497.45 ± 9.64; BP 719.72 ± 11.37) and CYP2D6 (IC₅₀ [µg/mL]: VF 637.15 ± 14.78, BP 588.70 ± 11.01). These results support the potential reuse of O. majorana stems as a sustainable source of bioactive compounds for nutraceutical and health-related applications. Full article

EGFR is the most frequently altered driver gene in non-small-cell lung cancer (NSCLC), and its overexpression is also associated with breast cancer. In the present study, we synthesized 18 new compounds (B-1, B-2, B-6, B-7, and BP-1–14). The cytotoxicity of these compounds was evaluated in A549 NSCLC and MCF-7 breast cancer cells, as well as in Jurkat cells and PBMCs (healthy). The most potent compounds were further examined for their ability to induce apoptosis in A549 and MCF-7 cells, as well as their EGFR inhibitory activity. Molecular docking was conducted at the ATP-binding site of EGFR, and key pharmacokinetic and toxicity parameters were predicted in silico. B-2 demonstrated the strongest cytotoxicity against A549 and MCF-7 cells (IC₅₀ = 2.14 ± 0.83 μM and 8.91 ± 1.38 μM, respectively), displaying selective cytotoxicity between Jurkat cells and PBMCs (SI = 23.2). B-2 induced apoptosis in A549 and MCF-7 cells at rates of 16.8% and 4.3%, respectively. B-2 inhibited EGFR by 66% at a 10 μM concentration and showed a strong binding affinity to the ATP-binding site of EGFR. Furthermore, B-2 exhibited drug-like characteristics and was not identified as carcinogenic, genotoxic, or mutagenic. B-2 shows promise as an apoptosis inducer and EGFR inhibitor for future anti-NSCLC and anti-breast cancer research. Full article

This study aimed to investigate the underlying mechanisms by which dandelion extract inhibits the proliferation of breast cancer MDA-MB-231 cells. Dandelion root and leaf extracts were prepared using a heat reflux method and subjected to solvent gradient extraction to obtain fractions with different polarities. MTT assays revealed that the ethyl acetate fraction exhibited the strongest inhibitory effect on cell proliferation. LC-MS analysis identified 12 potential active compounds, including sesquiterpenes such as Isoalantolactone and Artemisinin, which showed significantly lower toxicity toward normal mammary epithelial MCF-10A cells compared to tumor cells (p < 0.01). Mechanistic studies demonstrated that the extract induced apoptosis in a dose-dependent manner, with an apoptosis rate as high as 85.04%, and significantly arrested the cell cycle at the S and G2/M phases. Label-free quantitative proteomics identified 137 differentially expressed proteins (|FC| > 2, p < 0.05). GO enrichment analysis indicated that these proteins were mainly involved in cell cycle regulation and apoptosis. KEGG pathway analysis revealed that the antitumor effects were primarily mediated through the regulation of PI3K-Akt (hsa04151), JAK-STAT (hsa04630), and PPAR (hsa03320) signaling pathways. Moreover, differential proteins such as PI3K, AKT1S1, SIRT6, JAK1, SCD, STAT3, CASP8, STAT2, STAT6, and PAK1 showed strong correlation with the core components of the EA-2 fraction of dandelion. Molecular docking results demonstrated that these active compounds exhibited strong binding affinities with key target proteins such as PI3K and JAK1 (binding energy < −5.0 kcal/mol). This study elucidates the multi-target, multi-pathway synergistic mechanisms by which dandelion extract inhibits breast cancer, providing a theoretical basis for the development of novel antitumor agents. Full article

Marine algae offer environmentally friendly platforms for green nanoparticle synthesis. This study reports the biosynthesis of silver nanoparticles using polysaccharides isolated from the brown alga Chnoospora minima (PAgNPs) and evaluates their therapeutic potential. Fourier Transform Infrared Spectroscopy (FTIR) confirmed algal polysaccharide functional groups. Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray (EDX) analysis characterized the nanoparticles as spherical (~84 nm average size), stable (zeta potential −18.5 mV), and containing elemental silver without nitrogen. The PAgNPs exhibited potent antioxidant activity (~100% DPPH scavenging) and significant antimicrobial efficacy, particularly against Staphylococcus aureus and Candida species. Crucially, PAgNPs displayed potent antiproliferative activity against human lung cancer cells (A549, IC₅₀: 13.59 µg/mL). In contrast, toxicity to normal Vero cells was significantly lower (IC₅₀: 300.2 µg/mL), demonstrating notable cancer cell selectivity (SI 22.1). Moderate activity was observed against MCF-7 breast cancer cells (IC₅₀: 100.7 µg/mL). These results demonstrate that C. minima polysaccharide facilitates the synthesis of biocompatible AgNPs with promising antimicrobial and selective anticancer capabilities, highlighting their potential for further development as nanotherapeutics. Full article

The use of mineral fertilisers has increased in recent years, but this has had a negative effect on the environment, including causing the water in rivers and lakes to become too rich in nutrients, a process known as eutrophication. Current research focuses on producing fertiliser materials that are environmentally friendly. The aim of this study was to examine the impact of novel specialised organic-mineral fertilisers (OMFs: NP 24-12, NP 10-10, and NP 10-10 Zn⁺) on the yield and chemical composition of maize. These fertilisers were compared with a control (no fertiliser) and with other fertilisers (mixture of commercial fertilisers (MCFs): NP 24-12 and NP 10-10) that were used as a reference. All fertilisers increased the SPAD index at the fifth leaf unfolded stage of maize, with the majority (apart from OMF NP 10-10) also increasing it at the panicle emergence stage. MCF NP 10-10 had the most positive effect on the plant height, while OMF NP 10-10 had the least positive effect. All fertilisers had a positive effect on maize growth and development, with MCFs NP 10-10 and NP 24-12 having by far the strongest effect on increasing crop yields. The yield of plants fertilised with OMFs NP 24-12, NP 10-10, and NP 10-10 Zn⁺ was lower than the yields of plants fertilised with MCF NP 24-12 and MCF NP 10-10. OMF NP 10-10 caused a greater increase in the contents of all elements, and OMF NP 24-12 caused a greater increase in most elements (except P and Ca) in maize than MCFs did at an identical NP ratio. OMF NP 10-10 Zn⁺ was found to have a significant impact on the mineral composition of maize, resulting in a decline in Ca and P levels, along with a notable increase in Mg, Zn, and Cu concentrations. The most significant differences were observed for Cu and Zn. The OMFs, notably NP 24-12 and NP 10-10, exhibited a comparatively diminished acidifying impact in comparison with the MCFs. The application of fertilisers resulted in a significant increase in soil nutrient levels, with most fertilisers increasing the soil N, P, and Zn contents. Additionally, the OMFs led to an increase in Cu. However, MCFs NP 24-12 and NP 10-10 reduced the soil Cu and Mn contents. Studies should include other species as they have different needs. Field experiments are also needed. Full article

Nucleolin (NCL), an RNA-binding protein which regulates critical cellular processes, is frequently dysregulated in human cancers, including breast cancer, making it an attractive therapeutic target. However, molecular details of the RNA-NCL interaction have not been investigated yet. A tRNA fragment named tRF3E, displaying tumor suppressor roles in breast cancer, was found to bind NCL with high affinity displacing NCL-controlled transcripts. Here, we investigated the determinants and cooperativity of tRF3E-NCL interaction by Electrophoretic Mobility Shift Assays and in silico docking analysis, using wild-type or mutated tRF3E. We found that NCL, through its RNA-binding domains (RBD1–2 and RBD3–4), binds simultaneously two tRF3E molecules, giving rise to an energetically favored complex. Instead, a mutant form of tRF3E (M19–24), in which the NCL recognition element in position 19–24 has been disrupted, contacts NCL exclusively at RBD3–4, causing the loss of cooperativity among RBDs. Importantly, when expressed in MCF7 breast cancer cells, tRF3E significantly reduced cell proliferation and colony formation, confirming its role as tumor suppressor, but tRF3E functional properties were lost when the 19–24 motif was mutated, suggesting that cooperativity among multiple domains is required for the NCL-mediated tRF3E antitumor function. This study sheds light on the dynamic of RNA-NCL interaction and lays the foundations for using tRF3E as a promising NCL-targeted biodrug candidate. Full article