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Methotrexate (MTX) is a folic acid antagonist routinely used in cancer treatment, characterized by poor water solubility and low skin permeability. These issues could be mitigated by using drug delivery systems, such as functionalized gold nanoparticles (AuNPs), known for their versatility and unique properties. This study aimed to develop multi-shell AuNPs functionalized with MTX for the improvement of MTX antitumoral, antioxidant, and biocompatibility features. Stable phosphine-coated AuNPs were synthesized and functionalized with tailored polyethylene glycol (PEG) and short-branched polyethyleneimine (PEI) moieties, followed by MTX covalent binding. Physicochemical characterization by UV–vis and Fourier-transform infrared spectroscopy (FTIR) spectroscopy, dynamic light scattering (DLS), scanning transmission electron microscopy (STEM), and X-ray photoelectron spectroscopy (XPS) confirmed the synthesis at each step. The antioxidant activity of functionalized AuNPs was determined using DPPH radical scavenging assay, ferric ions' reducing antioxidant power (FRAP), and cupric reducing antioxidant capacity (CUPRAC) assays. Biocompatibility and cytotoxicity were assessed using MTT and LDH assays on HaCaT human keratinocytes and CAL27 squamous cell carcinoma. MTX functionalized AuNPs demonstrated enhanced antioxidant activity and a pronounced cytotoxic effect on the tumoral cells compared to their individual components, highlighting their potential for improving cancer therapy. [ABSTRACT FROM AUTHOR]

Rhus typhina, an invasive plant species, contains valuable compounds that can be utilized in various fields. The main aim of this paper was to find the optimal conditions for extracting high amounts of bioactive compounds from R. typhina fruits using ultrasound-assisted and bead-beating techniques under different parameters (solvent concentration, solvent/solid ratio, extraction time, bead size, and material). A Box–Behnken design was applied for ultrasound-assisted extraction. The following process parameters were found to be optimal: 20/1 solvent/solid ratio (v/w), 61.51% aqueous ethanol, 10 min extraction time, with a composite desirability of 0.7719. The HPLC profile indicates that p-coumaric acid was the most abundant phenolic compound found in the BBE extract. The BBE extract was subjected to in vitro biological tests. The results indicate a high antimicrobial activity on Streptococcus pyogenes (20 mm inhibition zone) and Salmonella enterica (12 mm inhibition zone). A hemolysis rate of 19.85% was found at an extract concentration of 1000 µg/mL on sheep erythrocytes. We report for the first time the protective role of the extract on cell viability of human gingival fibroblasts, but also a weak antiproliferative effect on the HepG2 human liver cancer cell line. Overall, we conclude that R. typhina fruits are rich in bioactive compounds that can be recovered using proper extraction conditions. Further research is required to understand and valorize their biological potential. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria (LAB) produce important metabolites during fermentation processes, such as exopolysaccharides (EPS), which represent powerful natural antioxidants. On the other hand, H. sabdariffa L. anthocyanin extracts protect LAB and support their development. This study uncovers for the first time, the antioxidant profile of Weissella confusa PP29 probiotic media and focuses on elevating its impressive antioxidant attributes by synergistically integrating H. sabdariffa L. anthocyanin extract. The multifaceted potential of this innovative approach is explored and the results are remarkable, allowing us to understand the protective capacity of the fermented product on the intestinal mucosa. The total phenolic content was much lower at the end of the fermentation process compared to the initial amount, confirming their LAB processing. The DPPH radical scavenging and FRAP of the fermented products were higher compared to ascorbic acid and antioxidant extracts, while superoxide anion radical scavenging and lipid peroxidation inhibitory activity were comparable to that of ascorbic acid. The antioxidant properties of the fermented products were correlated with the initial inoculum and anthocyanin concentrations. All these properties were preserved for 6 months, demonstrating the promising efficacy of this enriched medium, underlining its potential as a complex functional food with enhanced health benefits. [ABSTRACT FROM AUTHOR]

This manuscript presents the synthesis, structural characterization, and antitumor evaluation of new monoquaternary salts derived from various N-heterocycles. For quinoline and quinoxaline, respectively, unexpected H-bonded mixtures of the reactants have been obtained. To assess their potential antitumor activity, the comprehensive panel of NCI's 60 human cancer cell lines was employed. Remarkably, mixtures 3g and 3h displayed significant inhibitory activity against leukemia, melanoma, and colon cancer cell lines. Furthermore, mixtures 3g and 3h displayed good cytotoxicity on MCF7 breast cancer cells, but not on normal fibroblasts, at 2.5 x 10-5 M, showing promise for the therapeutic applications. [ABSTRACT FROM AUTHOR]

The correction notice in the journal Pharmaceutics addresses errors in Figure 2 and references [208] and [33] in the original publication by Simionescu et al. The cited article regarding miR-34a was retracted, leading to inaccuracies in the publication. The authors confirm that the scientific conclusions remain unchanged, and the correction has been approved by the Academic Editor. [Extracted from the article]

We hypothesized that the mechanism responsible for the anti-atherosclerotic action of bilberry extract (BE) is linked to its antioxidant and anti-inflammatory potential, and investigated its direct effect on the regulation of apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP) secretion from lipid-loaded macrophages. Human THP-1 macrophages were loaded with lipids by incubation with human copper-oxidized LDL (oxLDL) and then exposed to different concentrations of BE (1–5 µg mL −1) obtained from bilberries (mechanically homogenized and solubilized in ethanol). Cellular and secreted proteins, the phosphorylation level of NF-κB and protein kinase A (PKA) were quantified by Western blot and gene expression was evaluated by Real-time PCR. The results showed that BE induced in lipid-loaded macrophages has: (i) an antioxidant effect by reducing the expression of NADPH oxidase subunits, p22 phox, p47 phox and NOX4, (ii) an anti-inflammatory effect by diminishing the secretion of CRP, MCP-1 and IL-1β and (iii) cholesterol efflux by increasing the secretion of apoE and CETP and by reducing cellular cholesterol content. BE exerted these effects by inhibition of NF-κB and activation of PKA signaling pathways. Our study supports BE therapeutic administration to decrease oxidative and inflammatory stress by a molecular mechanism regulated by NF-κB and PKA signaling pathways in lipid-loaded macrophages. [ABSTRACT FROM AUTHOR]

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained. [ABSTRACT FROM AUTHOR]