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Search Results (617)

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25 pages, 2959 KiB  
Article
Synthesis, Characterization, HSA/DNA Binding, and Cytotoxic Activity of [RuCl26-p-cymene)(bph-κN)] Complex
by Stefan Perendija, Dušan Dimić, Thomas Eichhorn, Aleksandra Rakić, Luciano Saso, Đura Nakarada, Dragoslava Đikić, Teodora Dragojević, Jasmina Dimitrić Marković and Goran N. Kaluđerović
Molecules 2025, 30(15), 3088; https://doi.org/10.3390/molecules30153088 - 23 Jul 2025
Viewed by 234
Abstract
A novel ruthenium(II) complex, [RuCl26-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and [...] Read more.
A novel ruthenium(II) complex, [RuCl26-p-cymene)(bph-κN)] (1), was synthesized and structurally characterized using FTIR and NMR spectroscopy. Density functional theory (DFT) calculations supported the proposed geometry and allowed for comparative analysis of experimental and theoretical spectroscopic data. The interaction of complex 1 with human serum albumin (HSA) and calf thymus DNA was investigated through fluorescence quenching experiments, revealing spontaneous binding driven primarily by hydrophobic interactions. The thermodynamic parameters indicated mixed quenching mechanisms in both protein and DNA systems. Ethidium bromide displacement assays and molecular docking simulations confirmed DNA intercalation as the dominant binding mode, with a Gibbs free binding energy of −34.1 kJ mol−1. Antioxidant activity, assessed by EPR spectroscopy, demonstrated effective scavenging of hydroxyl and ascorbyl radicals. In vitro cytotoxicity assays against A375, MDA-MB-231, MIA PaCa-2, and SW480 cancer cell lines revealed selective activity, with pancreatic and colorectal cells showing the highest sensitivity. QTAIM analysis provided insight into metal–ligand bonding characteristics and intramolecular stabilization. These findings highlight the potential of 1 as a promising candidate for further development as an anticancer agent, particularly against multidrug-resistant tumors. Full article
(This article belongs to the Special Issue Transition Metal Complexes with Bioactive Ligands)
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20 pages, 2983 KiB  
Article
Chnoospora minima Polysaccharide-Mediated Green Synthesis of Silver Nanoparticles: Potent Anticancer and Antimicrobial Activities
by Lakshika Keerthirathna, Sachini Sigera, Milan Rathnayake, Arunoda Senarathne, Hiruni Udeshika, Chamali Kodikara, Narayana M. Sirimuthu, Kalpa W. Samarakoon, Mohamad Boudjelal, Rizwan Ali and Dinithi C. Peiris
Biology 2025, 14(7), 904; https://doi.org/10.3390/biology14070904 - 21 Jul 2025
Viewed by 491
Abstract
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. [...] Read more.
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
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17 pages, 2071 KiB  
Article
Melatonin Enhances Drought Tolerance by Regulating the Genes Underlying Photosynthesis and Antioxidant Defense in Rubber Tree (Hevea brasiliensis) Seedlings
by Dejun Li, Zhihui Xia, Xuncheng Wang, Hong Yang and Yao Li
Plants 2025, 14(14), 2243; https://doi.org/10.3390/plants14142243 - 21 Jul 2025
Viewed by 381
Abstract
Melatonin (MT) can enhance plant stress tolerance by activating the internal defense system, but its application in rubber trees has been barely reported up to now. In this study, we found that the relative electrical conductivity (REC), H2O2, and [...] Read more.
Melatonin (MT) can enhance plant stress tolerance by activating the internal defense system, but its application in rubber trees has been barely reported up to now. In this study, we found that the relative electrical conductivity (REC), H2O2, and malondialdehyde (MDA) contents were significantly higher in the leaves of rubber tree seedlings under drought stress compared to the control (water treatment), whereas chlorophyll contents were obviously lower in the leaves under drought stress compared to the control. MT partly relieves the aforementioned drought-induced adverse effects by dramatically reducing chlorophyll degradation, H2O2 accumulation, MDA content, and REC. Comparative transcriptomes among the PEG (P), MT (M), and PEG + MT (PM) treatments against the control showed that 213, 896, and 944 genes were differently expressed in rubber tree seedlings treated with M, P, and PM in contrast to the control. Among the 64 differently expressed genes (DEGs) being common among the three comparisons, the expression profiles of 25 were opposite in MH compared with PH. Intriguingly, all the KEGG pathways of the DEGs mentioned above belonged to metabolism including energy metabolism, carbohydrate metabolism, amino acid metabolism, and the metabolism of cofactors and vitamins. Exogenous application of MT mainly regulated the genes associated with photosynthesis and the anti-oxidative defense system, thereby enhancing the antioxidant protection of rubber tree seedlings under drought stress. These results suggest that exogenous melatonin application can effectively enhance drought tolerance by heightening ROS scavenging to decrease H2O2 accumulation in rubber tree seedlings. Our results elucidate the molecular mechanisms of MT’s roles in drought stress, which help to employ exogenous MT to boost drought tolerance in the rubber tree. Full article
(This article belongs to the Special Issue Metabolic Analysis of Plant Development and Defense Responses)
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18 pages, 7598 KiB  
Article
Recovery of Fine Rare Earth Minerals from Simulated Tin Tailings by Carrier Magnetic Separation: Selective Heterogeneous Agglomeration with Coarse Magnetite Particles
by Ilhwan Park, Topan Satria Gumilang, Rinaldi Yudha Pratama, Sanghee Jeon, Carlito Baltazar Tabelin, Theerayut Phengsaart, Muhammad Bilal, Youhei Kawamura and Mayumi Ito
Minerals 2025, 15(7), 757; https://doi.org/10.3390/min15070757 - 19 Jul 2025
Viewed by 331
Abstract
The demand for rare earth elements (REEs) is continuously increasing due to the important roles they play in low-carbon and green energy technologies. Unfortunately, the global REE reserves are limited and concentrated in only a few countries, so the reprocessing of alternative resources [...] Read more.
The demand for rare earth elements (REEs) is continuously increasing due to the important roles they play in low-carbon and green energy technologies. Unfortunately, the global REE reserves are limited and concentrated in only a few countries, so the reprocessing of alternative resources like tailings is of critical importance. This study investigated carrier magnetic separation using coarse magnetite particles as a carrier to recover finely ground monazite from tailings. The monazite and carrier surfaces were modified by sodium oleate (NaOL) to improve the hydrophobic interactions between them. The results of zeta potential and contact angle measurements implied the selective adsorption of NaOL onto the surfaces of the monazite and magnetite particles. Although their hydrophobicity increased, heterogenous agglomeration between them was not substantial. To improve heterogenous agglomeration, emulsified kerosene was utilized as a bridging liquid, resulting in more extensive attachment of fine monazite particles onto the surfaces of carrier particles and a dramatic improvement in monazite recovery by magnetic separation—from 0% (without carrier) to 70% (with carrier). A rougher–scavenger–cleaner carrier magnetic separation can produce REE concentrates with a total rare earth oxide (TREO) recovery of 80% and a grade of 9%, increased from 3.4%, which can be further increased to 23.2% after separating REEs and the carrier. Full article
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18 pages, 2417 KiB  
Article
Multifaceted Applications of Zerumbone-Loaded Metal–Organic Framework-5: Anticancer, Antibacterial, Antifungal, DNA-Binding, and Free Radical Scavenging Potentials
by Sumeyya Deniz Aybek, Mucahit Secme, Hasan Ilhan, Leyla Acik, Suheyla Pinar Celik and Gonca Gulbay
Molecules 2025, 30(14), 2936; https://doi.org/10.3390/molecules30142936 - 11 Jul 2025
Viewed by 305
Abstract
In the present research, metal–organic framework-5 (MOF-5) was synthesized and loaded with zerumbone (ZER@MOF-5), followed by the evaluation of its anticancer, antibacterial, antifungal, DNA-binding, and free radical scavenging potentials. The synthesized nanoparticles were characterized using X-ray diffraction, ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive [...] Read more.
In the present research, metal–organic framework-5 (MOF-5) was synthesized and loaded with zerumbone (ZER@MOF-5), followed by the evaluation of its anticancer, antibacterial, antifungal, DNA-binding, and free radical scavenging potentials. The synthesized nanoparticles were characterized using X-ray diffraction, ultraviolet–visible spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. The in vitro anticancer activity of ZER@MOF-5 was studied in a human breast cancer cell line (MCF-7) using the CCK-8 assay. The interaction of ZER@MOF-5 with pBR322 plasmid DNA was assessed by gel electrophoresis. The antimicrobial effect of ZER@MOF-5 was examined in gram-positive and gram-negative bacterial strains and yeast strains using the microdilution method. The free radical scavenging activity was assessed using the DPPH assay. Cytotoxicity assay revealed a notable enhancement in the anticancer activity of zerumbone upon its encapsulation into MOF-5. The IC50 value for ZER@MOF-5 was found to be 57.33 µg/mL, which was lower than that of free zerumbone (IC50: 89.58 µg/mL). The results of the DNA-binding experiment indicate that ZER@MOF-5 can bind to target DNA and cause a conformational change in DNA. The results of the antibacterial activity experiment showed that the antibacterial ability of ZER@MOF-5 was limited compared to free zerumbone. The results of the DPPH assay demonstrated that the antioxidant activity of free zerumbone was higher than that of ZER@MOF-5. MOFs encapsulate compounds within their porous crystalline structure, which leads to prolonged circulation time compared to single ligands. Although the unique structure of MOFs may limit their antibacterial and antioxidant activity in the short term, it may increase therapeutic efficacy in the long term. However, to fully understand the long-term antibacterial and antioxidant effects of the ZER@MOF-5, further comprehensive in vitro and in vivo experiments are necessary. This finding indicates that the MOF-5 could potentially be an impressive carrier for the oral administration of zerumbone. Full article
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58 pages, 656 KiB  
Review
Human Digestive Physiology and Evolutionary Diet: A Metabolomic Perspective on Carnivorous and Scavenger Adaptations
by Vicente Javier Clemente-Suárez, Laura Redondo-Flórez, Ana Isabel Beltrán-Velasco, Rodrigo Yáñez-Sepúlveda, Alejandro Rubio-Zarapuz, Alexandra Martín-Rodríguez, Eduardo Navarro-Jimenez and José Francisco Tornero-Aguilera
Metabolites 2025, 15(7), 453; https://doi.org/10.3390/metabo15070453 - 4 Jul 2025
Viewed by 1671
Abstract
This review examines human digestive physiology and metabolic adaptations in the context of evolutionary dietary patterns, particularly those emphasizing carnivorous and scavenging behaviors. By integrating metabolomic data with archaeological, anatomical, and microbiological evidence, the study explores how early hominins adapted to intermittent but [...] Read more.
This review examines human digestive physiology and metabolic adaptations in the context of evolutionary dietary patterns, particularly those emphasizing carnivorous and scavenging behaviors. By integrating metabolomic data with archaeological, anatomical, and microbiological evidence, the study explores how early hominins adapted to intermittent but energy-dense animal-based diets. The analysis highlights the development of hepatic insulin resistance, enhanced fat and protein metabolism, and shifts in gut microbiota diversity as physiological signatures of meat consumption. Comparative evaluations of digestive enzyme profiles, intestinal morphology, and salivary composition underscore humans’ omnivorous flexibility and partial carnivorous specialization. Additionally, biomarkers such as ketone bodies, branched-chain amino acids, and trimethylamine-N-oxide are identified as metabolic indicators of habitual meat intake. These adaptations, though once evolutionarily advantageous, are discussed in relation to current metabolic disorders in modern nutritional contexts. Overall, this review presents a metabolomic framework for understanding the evolutionary trajectory of human digestion and its implications for health and dietary recommendations. Full article
(This article belongs to the Section Advances in Metabolomics)
16 pages, 2188 KiB  
Article
Tartary Buckwheat Peptides Prevent Oxidative Damage in Differentiated SOL8 Cells via a Mitochondria-Mediated Apoptosis Pathway
by Yifan Xu, Yawen Wang, Min Yang, Pengxiang Yuan, Weikang Xu, Tong Jiang and Jian Huang
Nutrients 2025, 17(13), 2204; https://doi.org/10.3390/nu17132204 - 2 Jul 2025
Viewed by 479
Abstract
Background: Under oxidative stress conditions, the increased levels of reactive oxygen species (ROS) within cells disrupt the intracellular homeostasis. Tartary buckwheat peptides exert their effects by scavenging oxidative free radicals, such as superoxide anion and hydrogen peroxide, thereby reducing oxidative damage within cells. [...] Read more.
Background: Under oxidative stress conditions, the increased levels of reactive oxygen species (ROS) within cells disrupt the intracellular homeostasis. Tartary buckwheat peptides exert their effects by scavenging oxidative free radicals, such as superoxide anion and hydrogen peroxide, thereby reducing oxidative damage within cells. Meanwhile, these peptides safeguard mitochondria by maintaining the mitochondrial membrane potential, decreasing the production of mitochondrial oxygen free radicals, and regulating mitochondrial biogenesis and autophagy to preserve mitochondrial homeostasis. Through these mechanisms, Tartary buckwheat peptides restore the intracellular redox balance, sustain cellular energy metabolism and biosynthesis, and ensure normal cellular physiological functions, which is of great significance for cell survival and adaptation under oxidative stress conditions. Objectives: In this experiment, a classical cellular oxidative stress model was established. Indicators related to antioxidant capacity and mitochondrial membrane potential changes, as well as pathways associated with oxidative stress, were selected for detection. The aim was to elucidate the effects of Tartary buckwheat oligopeptides on the metabolism of cells in response to oxidative stress. Methods: In this study, we established an oxidative damage model of mouse skeletal muscle myoblast (SOL8) cells using hydrogen peroxide (H2O2), investigated the pre-protective effects of Tartary buckwheat oligopeptides on H2O2-induced oxidative stress damage in SOL8 cells at the cellular level, and explored the possible mechanisms. The CCK-8 method is a colorimetric assay based on WST-8-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodiumsalt], which is used to detect cell proliferation and cytotoxicity. Results: The value of CCK-8 showed that, when the cells were exposed to 0.01 mmol/L H2O2 for 1 h and 10 mg/mL Tartary buckwheat oligopeptides intervention for 48 h, these were the optimal conditions. Compared with the H2O2 group, the intervention group (KB/H2O2 group) showed that the production of ROS was significantly reduced (p < 0.001), the malondialdehyde (MDA) content was significantly decreased (p < 0.05), and the activity of catalase (CAT) was significantly increased (p < 0.01); the mitochondrial membrane potential in the KB/H2O2 group tended to return to the level of the control group, and they all showed dose-dependent effects. Compared with the H2O2 group, the mRNA expression of KEAP1 in the KB/H2O2 group decreased, while the mRNA expression of NRF2α, HO-1, nrf1, PGC-1, P62, and PINK increased. Conclusions: Therefore, Tartary buckwheat oligopeptides have a significant pre-protective effect on H2O2-induced SOL8 cells, possibly by enhancing the activity of superoxide dismutase, reducing ROS attack, balancing mitochondrial membrane potential, and maintaining intracellular homeostasis. Full article
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19 pages, 1591 KiB  
Article
Sequential Extraction of Bioactive Saponins from Cucumaria frondosa Viscera: Supercritical CO2–Ethanol Synergy for Enhanced Yields and Antioxidant Performance
by Jianan Lin, Guangling Jiao and Azadeh Kermanshahi-pour
Mar. Drugs 2025, 23(7), 272; https://doi.org/10.3390/md23070272 - 28 Jun 2025
Viewed by 525
Abstract
This study investigates the sequential extraction of lipids and saponins from C. frondosa viscera. Lipids were extracted using supercritical carbon dioxide (scCO2) in the presence of ethanol (EtOH) as a co-solvent. Subsequently, the lipid-extracted viscera underwent three saponin extraction approaches, scCO [...] Read more.
This study investigates the sequential extraction of lipids and saponins from C. frondosa viscera. Lipids were extracted using supercritical carbon dioxide (scCO2) in the presence of ethanol (EtOH) as a co-solvent. Subsequently, the lipid-extracted viscera underwent three saponin extraction approaches, scCO2-scCO2, scCO2-EtOH, and scCO2-hot water, resulting in saponin-rich extracts. Process parameter investigation for saponin extraction from scCO2-defatted viscera revealed minimal effects of temperature, pressure, extraction time, static extraction, and EtOH concentration on saponin yields, allowing for milder operational conditions (35 °C, 20 MPa, 30 min dynamic extraction, 75% EtOH at 0.5 mL/min) to achieve energy-efficient recovery. Continuous EtOH feeding predominates the scCO2 extraction of saponins. The sequential scCO2 extraction of lipid and saponins yielded saponins at 9.13 mg OAE/g, while scCO2 extraction of lipid followed by a 24 h 70% EtOH extraction of saponins achieved 16.26 mg OAE/g, closely matching the optimized ultrasonic-assisted extraction of saponins (17.31 mg OAE/g) from hexane-defatted samples. Antioxidant activities of saponin-rich extracts obtained in the sequential scCO2-EtOH extraction (17.12 ± 4.20% DPPH scavenging) and the sequential scCO2-scCO2 extraction (16.14 ± 1.98%) were comparable to BHT (20.39 ± 0.68%), surpassing that of hexane-defatted ultrasonic extracts (8.11 ± 1.16%). The optimized scCO2-EtOH method offers a sustainable alternative, eliminating toxic solvents while maintaining high saponin yields and bioactivity. Full article
(This article belongs to the Special Issue Marine Biorefinery for Bioactive Compounds Production)
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22 pages, 3229 KiB  
Article
Tyrosine 67 Phosphorylation Controls Respiration and Limits the Apoptotic Functions of Cytochrome c
by Junmei Wan, Paul T. Morse, Matthew P. Zurek, Alice A. Turner, Asmita Vaishnav, Arthur R. Salomon, Brian F. P. Edwards, Tasnim Arroum and Maik Hüttemann
Cells 2025, 14(13), 951; https://doi.org/10.3390/cells14130951 - 21 Jun 2025
Viewed by 514
Abstract
Cytochrome c (Cytc) is a multifunctional protein, essential for respiration and intrinsic apoptosis. Post-translational modifications of Cytc have been linked to physiological and pathophysiologic conditions, including cancer. Cytc tyrosine 67 (Y67) is a conserved residue that is important to [...] Read more.
Cytochrome c (Cytc) is a multifunctional protein, essential for respiration and intrinsic apoptosis. Post-translational modifications of Cytc have been linked to physiological and pathophysiologic conditions, including cancer. Cytc tyrosine 67 (Y67) is a conserved residue that is important to the structure and function of Cytc. We here report the phosphorylation of Y67 of Cytc purified from bovine heart mapped by mass spectrometry. We characterized the functional effects of Y67 Cytc modification using in vitro and cell culture models. Y67 was mutated to the phosphomimetic glutamate (Y67E) and to phenylalanyl (Y67F) as a control. The phosphomimetic Y67E Cytc inhibited cytochrome c oxidase (COX) activity, redirecting energy metabolism toward glycolysis, and decreased the pro-apoptotic capabilities of Cytc. The phosphomimetic Y67E Cytc showed a significantly impaired rate of superoxide scavenging and a reduced rate of oxidation by hydrogen peroxide, suggesting a lower ability to transfer electrons and scavenge reactive oxygen species (ROS). Phosphomimetic Y67E replacement led to an almost complete loss of cardiolipin peroxidase activity, pointing to a central role of Y67 for this catalytic function of Cytc. In intact cells, phosphomimetic replacement leads to a reduction in cell respiration, mitochondrial membrane potential, and ROS levels. We propose that Y67 phosphorylation is cardioprotective and promotes cell survival. Full article
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17 pages, 1433 KiB  
Article
Insights into Chemopreventive Effects of Rosmarinic Acid Against Aflatoxin B1-Induced Genotoxic Effects
by Veronika Furlan, Matjaž Novak, Martina Štampar, Alja Štern, Bojana Žegura and Urban Bren
Foods 2025, 14(12), 2111; https://doi.org/10.3390/foods14122111 - 16 Jun 2025
Viewed by 407
Abstract
In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation [...] Read more.
In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. Full article
(This article belongs to the Special Issue Potential Health Benefits of Plant Food-Derived Bioactive Compounds)
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15 pages, 2012 KiB  
Article
Food Grade Synthesis of Hetero-Coupled Biflavones and 3D-Quantitative Structure–Activity Relationship (QSAR) Modeling of Antioxidant Activity
by Hongling Zheng, Xin Yang, Qiuyu Zhang, Joanne Yi Hui Toy and Dejian Huang
Antioxidants 2025, 14(6), 742; https://doi.org/10.3390/antiox14060742 - 16 Jun 2025
Viewed by 548
Abstract
Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional [...] Read more.
Biflavonoids are a unique subclass of dietary polyphenolic compounds known for their diverse bioactivities. Despite these benefits, these biflavonoids remain largely underexplored due to their limited natural availability and harsh conditions required for their synthesis, which restricts broader research and application in functional foods and nutraceuticals. To address this gap, we synthesized a library of rare biflavonoids using a radical–nucleophile coupling reaction previously reported by our group. The food grade coupling reaction under weakly alkaline water at room temperature led to isolation of 28 heterocoupled biflavones from 11 monomers, namely 3′,4′-dihydroxyflavone, 5,3′,4′-trihydroxyflavone, 6,3′,4′-trihydroxyflavone, 7,3′,4′-trihydroxyflavone, diosmetin, chrysin, acacetin, genistein, biochanin A, and wogonin. The structures of the dimers are characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectroscopy (HRMS). In addition, we evaluated the antioxidant potential of these biflavones using a DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay and the DPPH value ranges between 0.75 to 1.82 mM of Trolox/mM of sample across the 28 synthesized dimers. Additionally, a three-dimensional quantitative structure–activity relationship (3D-QSAR) analysis was conducted to identify structural features associated with enhanced antioxidant activity. The partial least squares (PLS) regression QSAR model showed acceptable r2 = 0.936 and q2 = 0.869. Additionally, the average local ionization energy (ALIE), electrostatic potential (ESP), Fukui index (F-), and electron density (ED) were determined to identify the key structural moiety that was capable of donating electrons to neutralize reactive oxygen species. Full article
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16 pages, 1568 KiB  
Article
Exploring the Catalytic Mechanisms of a Newly Identified Salt-Activated Alginate Lyase from Pseudoalteromonas carrageenovora ASY5
by Xiaoyan Zhuang, Chao Jiao, Zewang Guo, Qiong Xiao, Jun Chen, Fuquan Chen, Qiuming Yang, Yi Ru, Huifen Weng, Siyuan Wang, Anfeng Xiao and Yonghui Zhang
Mar. Drugs 2025, 23(6), 254; https://doi.org/10.3390/md23060254 - 15 Jun 2025
Viewed by 543
Abstract
Alginate lyases are critical enzymes in hydrolyzing alginate into alginate oligosaccharides (AOS), which are bioactive compounds known for their antioxidant properties and ability to lower serum glucose and lipid concentrations. However, elucidating catalytic mechanisms and discovering enzymes with enhanced catalytic efficiency remain long-term [...] Read more.
Alginate lyases are critical enzymes in hydrolyzing alginate into alginate oligosaccharides (AOS), which are bioactive compounds known for their antioxidant properties and ability to lower serum glucose and lipid concentrations. However, elucidating catalytic mechanisms and discovering enzymes with enhanced catalytic efficiency remain long-term challenges. Here, we report AlgL2491, a novel bifunctional and cold-adapted alginate lyase from Pseudoalteromonas carrageenovora ASY5, belonging to the polysaccharide lyase family 18. This enzyme uniquely cleaves both polyguluronic (polyG) and polymannuronic (polyM), predominantly releasing disaccharides, trisaccharides, and tetrasaccharides after 12 h of hydrolysis. The enzyme achieves peak catalytic efficiency at 35 °C and pH 7.5, with activity increasing 5.5-fold in 0.5 M of NaCl. Molecular dynamics simulations demonstrate that salt ions enhance structural stability by minimizing conformational fluctuations and strengthening interdomain interactions, providing mechanistic insights into its salt-activated behavior. The alginate oligosaccharides (AOS) exhibit excellent free radical-scavenging activities of 86.79 ± 0.31%, 83.42 ± 0.18%, and 71.28 ± 2.27% toward hydroxyl, ABTS, and DPPH radicals, with IC50 values of 8.8, 6.74, and 9.71 mg/mL, respectively. These findings not only reveal the salt-activation mechanism of AlgL2491 and highlight the potential value of its hydrolysate in antioxidant activity but also provide a sustainable industrial solution in industrial-scale AOS production directly from marine biomass, eliminating the need for energy-intensive desalination of alginate, which may inform future biocatalyst design for marine polysaccharide valorization. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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20 pages, 1211 KiB  
Review
Human CD36: Gene Regulation, Protein Function, and Its Role in Atherosclerosis Pathogenesis
by Monika Rac
Genes 2025, 16(6), 705; https://doi.org/10.3390/genes16060705 - 13 Jun 2025
Cited by 1 | Viewed by 1821
Abstract
Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The CD36 [...] Read more.
Human CD36 plays an important role in ligand binding, signalling, cell adhesion, and the regulation of angiogenesis. As a scavenging receptor, it is responsible for clearing long-chain fatty acids (LCFAs) and removing approximately 50% of oxidised low-density lipoprotein (ox-LDL) from plasma. The CD36 gene is alternatively spliced. It has several alternative promoters and first exons. The alternative transcripts are expressed in multiple tissues, and their expression patterns are highly variable. The molecular mechanisms that regulate CD36 gene expression are complex and reflect its multifunctional role in different tissues. CD36 activity has been linked to several metabolic processes, such as inflammation, angiogenesis, phagocytosis, and energy homeostasis. CD36 plays a key role in regulating vascular and cardiovascular health and in the pathogenesis of atherosclerosis. CD36 gene mutations in the Caucasian population are rare. Hence, it is extremely difficult to recruit a statistically significant group of CAD patients with these mutations. Nevertheless, this population is largely at risk of cardiovascular disease. Atherosclerosis is a multifactorial disease, but the role of the CD36 receptor in the development of ox-LDL is extremely important. This review aims to introduce readers to issues related to the relationship between CD36 and CAD. The activity of this receptor should be considered when exploring treatment options for atherosclerosis-related complications. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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30 pages, 6746 KiB  
Article
Microwave-Assisted Extraction of Bioactive Compounds from Mandarin Peel: A Comprehensive Biorefinery Strategy
by Marina Jurić, Nikolina Golub, Emerik Galić, Kristina Radić, Luna Maslov Bandić and Dubravka Vitali Čepo
Antioxidants 2025, 14(6), 722; https://doi.org/10.3390/antiox14060722 - 12 Jun 2025
Cited by 1 | Viewed by 532
Abstract
Mandarin peel is a valuable but underutilized source of numerous bioactive compounds. The main focus of this work was to develop an integrated two-step process for the subsequent extraction of polyphenols and carotenoids (step 1) and pectin (step 2) from mandarin peel by [...] Read more.
Mandarin peel is a valuable but underutilized source of numerous bioactive compounds. The main focus of this work was to develop an integrated two-step process for the subsequent extraction of polyphenols and carotenoids (step 1) and pectin (step 2) from mandarin peel by microwave-assisted extraction (MAE), using only green solvents. This represents a novel, scale-up-suitable approach that might contribute to the improved revalorization of mandarin peel. Response surface methodology was used to maximize the yields of polyphenols, flavonoids, and carotenoids, as well as antioxidative activity (DPPH- and ABTS-radical scavenging capacity). The sample-to-solvent ratio and solvent type significantly influenced extractability of polyphenols and carotenoids, while extraction time and power were the key variables influencing pectin yield. Optimal extracts contained 21.76 ± 0.46 mg GAE/g of polyphenols (with 139.7 ± 2.28 mg/g and 703.62 ± 51.72 µg/g of tangeretin and nobiletin, respectively); 352.3 ± 17.4 µg/g of β-carotene and 273 ± 23 mg/g of pectin. MAE resulted in either higher yields, reduced extraction times or both, compared to conventional solvent extraction (CSE), depending on the target compound. The energy consumption of MAE was considerably lower, compared to CSE, in four out of five developed extraction procedures. Pectin obtained in the integrated two-step process had higher purity compared to pectin extracted from intact mandarin peel. Full article
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13 pages, 1372 KiB  
Article
Phylogenetic Proximity vs. Environmental Adaptation: Exploring Photosynthetic Performances in Mediterranean and Andean Isolated Microalgae Under Different Light Intensities
by Giulio Panicucci, Carolina Chiellini, Cristiana Sbrana, Cristina Echeverría, Lorenzo Guglielminetti and Thais Huarancca Reyes
Phycology 2025, 5(2), 24; https://doi.org/10.3390/phycology5020024 - 11 Jun 2025
Viewed by 709
Abstract
The microalgal defense strategies for different white light intensities (70–700 μmol m−2 s−1) were investigated in isolates from unexplored habitats, focusing on photosynthetic performance. Chlorella sorokiniana strain F4 from a Mediterranean inland swamp and two strains related to Pectinodesmus pectinatus [...] Read more.
The microalgal defense strategies for different white light intensities (70–700 μmol m−2 s−1) were investigated in isolates from unexplored habitats, focusing on photosynthetic performance. Chlorella sorokiniana strain F4 from a Mediterranean inland swamp and two strains related to Pectinodesmus pectinatus (PEC) and Ettlia pseudoalveolaris (ETI) from an Ecuadorian highland lake were exposed to light over 18 h. The results showed that PSII photochemical efficiency was affected with increasing light due to photoinhibition or photodamage. F4 showed a low threshold of saturation light intensity, after which NPQ was compromised and total antioxidant levels were increased, leading to a reduction in its PSII photochemistry performance. F4 exhibited limited capacity for antennae reorganization in response to light stress. ETI and PEC differed in their photophysiological responses, although they came from the same habitat. ETI maintained high Chlb to Chla (i.e., large antennae), exhibited sustained energy dissipation, and preserved a high antioxidant pool (i.e., mycosporine-like amino acids) in all lights. Differently, in PEC, NPQ, antennae rearrangement, and reactive oxygen species scavenger pool were induced in a light-dependent manner. This study revealed the complex relationship between light parameters and microalgal physiology affected by environmental constraint adaptation and phylogenetic diversity. Full article
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