Molecules

17 pages, 848 KiB

Open AccessArticle

Targeted Restoration of T-Cell Subsets by a Fluorinated Piperazine Derivative β-Cyclodextrin Complex in Experimental Pulmonary Inflammation

by Valentina Yu, Marina Balabekova, Assel Ten, Tolganay Zharkynbek, Sulev Koks, Milana Alimova, Raushan Koizhaiganova, Meruyert Mussilim, Aigul Malmakova, Tulegen Seilkhanov and Khaidar Tassibekov

Molecules 2025, 30(13), 2741; https://doi.org/10.3390/molecules30132741 (registering DOI) - 25 Jun 2025

Abstract

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4⁺, CD4⁺CD25⁺, and CD4⁺CD25⁺FoxP3⁺, which are critical for immune regulation. This study evaluates the immunomodulatory potential of [...] Read more.

Acute pneumonia is frequently accompanied by immune suppression, particularly affecting T-cell subsets, such as CD4⁺, CD4⁺CD25⁺, and CD4⁺CD25⁺FoxP3⁺, which are critical for immune regulation. This study evaluates the immunomodulatory potential of a novel fluorinated piperazine-based aminophosphonate, complexed with β-cyclodextrin ((o-Fph)PPhβCD), comparing it with the clinically approved agent Polyoxidonium (PO) in a rat model of oleic acid-induced acute pneumonia. Flow cytometric analysis revealed that (o-Fph)PPhβCD significantly restored CD4⁺ and CD4⁺CD25⁺ T-cell levels and induced a sustained reduction in regulatory CD4⁺CD25⁺FoxP3⁺ cells, suggesting enhanced effector immune activity. While PO provided early immunorestorative effects, (o-Fph)PPhβCD exerted a more prolonged response, which was particularly evident by day 14. Structural confirmation of the inclusion complex was achieved through IR and NMR spectroscopy. These findings highlight (o-Fph)PPhβCD as a promising immunotherapeutic candidate that is capable of rebalancing immune cell populations and supporting host defense mechanisms during acute pulmonary inflammation. Full article

(This article belongs to the Special Issue Heterocycles: Design, Synthesis and Biological Evaluation, 3rd Edition)

25 pages, 3592 KiB

Open AccessFeature PaperArticle

Flavonoid Glycosides and Phenolic Acids from Inula Oculus-Christi Modulate Membrane Organization and Provide Antioxidant Protection

by Ralitsa Veleva, Tanya Topouzova-Hristova, Aneliya Kostadinova, Dayana Benkova, Antoaneta Trendafilova, Viktoria Ivanova, Veselina Moskova-Doumanova, Kirilka Mladenova, Jordan Doumanov, Vesela Yordanova and Galya Staneva

Molecules 2025, 30(13), 2740; https://doi.org/10.3390/molecules30132740 (registering DOI) - 25 Jun 2025

Abstract

Oxidative stress induces lipid peroxidation within the membrane bilayer, thereby compromising membrane integrity. Polyphenols (PPs), renowned for their antioxidant properties, have been shown to mitigate oxidative damage. Here, we investigated the structural and antioxidant effects of PPs—specifically flavonoid glycosides (FGs) and phenolic acids [...] Read more.

Oxidative stress induces lipid peroxidation within the membrane bilayer, thereby compromising membrane integrity. Polyphenols (PPs), renowned for their antioxidant properties, have been shown to mitigate oxidative damage. Here, we investigated the structural and antioxidant effects of PPs—specifically flavonoid glycosides (FGs) and phenolic acids (PAs)—extracted from Inula oculus-christi using steady-state fluorescence spectroscopy in both model and cell membranes. Membrane lipid order was evaluated using DPH and Laurdan spectroscopy, while DPH-TEMPO fluorescence quenching was employed to quantify raft-like domain formation in model systems. The antioxidant capacity of the PP extracts was assessed via fluorescence quenching of cis-parinaric acid. Both FGs and PAs conferred approximately 2-fold antioxidant protection, with FGs showing a 1.13-fold greater effect than PAs. In addition, both PP classes promoted lipid raft formation, particularly in cholesterol-rich membranes. PPs increased order in the liquid-disordered (L_d) phase while inducing disorder in the liquid-ordered (L_o) phase, depending on the lipid-to-PP ratio. Notably, FGs enhanced membrane fluidity more strongly in A549 than in MDCKII cells, as reflected by a ~5.7-fold decrease in Laurdan GP in A549 (from 0.04 to −0.17) versus a ~1.4-fold decrease in MDCKII at 200 μg/mL. These findings highlight the dual structural and antioxidative roles of FGs and PAs in preserving membrane integrity under oxidative stress. Full article

(This article belongs to the Special Issue Anti-inflammatory and Antioxidant Activities of Bioactive Compounds in Plants)

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15 pages, 573 KiB

Open AccessArticle

Phytochemical Profile and Selective Anticancer Activity of Parietaria judaica L. Extracts

by Izabela Bielecka, Dorota Natorska-Chomicka, Wioleta Dołomisiewicz, Arlindo Rodrigues Fortes and Katarzyna Dos Santos Szewczyk

Molecules 2025, 30(13), 2739; https://doi.org/10.3390/molecules30132739 (registering DOI) - 25 Jun 2025

Abstract

Parietaria judaica L. (alfavaca-de-cobra) was investigated as a potential source of anticancer compounds. Leaf extracts obtained using solvents of different polarities were evaluated for their phytochemical profiles and cytotoxic activities against a panel of human cancer cell lines (glioblastoma LN-229, lung NCI-H1563, breast [...] Read more.

Parietaria judaica L. (alfavaca-de-cobra) was investigated as a potential source of anticancer compounds. Leaf extracts obtained using solvents of different polarities were evaluated for their phytochemical profiles and cytotoxic activities against a panel of human cancer cell lines (glioblastoma LN-229, lung NCI-H1563, breast MDA-MB-231, liver HepG2, renal 769-P, cervical HeLa, and melanoma A-375) and a noncancerous HEK-293 cell line. LC-ESI-MS/MS analysis confirmed that the extracts are rich in polyphenols, including phenolic acids and flavonoids. Cytotoxicity was assessed via MTT and SRB assays, demonstrating dose-dependent antiproliferative effects. Among the extracts, the ethanolic fraction (PJ-E) exhibited the strongest cytotoxicity, with an IC₅₀ of 11.82 µg/mL against HeLa cells, while displaying a significantly higher IC₅₀ (139.42 µg/mL) against HEK-293, indicating tumor selectivity. The water extract (PJ-W) showed selective activity against lung cancer cells (IC₅₀ = 87.69 µg/mL), with minimal toxicity toward normal cells. The methanol/acetone extract (PJ-M) displayed intermediate activity, whereas the hexane extract (PJ-H) was the least effective. These findings highlight P. judaica, particularly its ethanolic extract, as a promising source of natural anticancer agents. Further research focusing on the isolation of active constituents, formulation development, and in vivo validation is warranted to support its therapeutic potential. Full article

(This article belongs to the Special Issue Isolation, Characterization, and Application of Anticancer Agents from Natural Products)

13 pages, 830 KiB

Open AccessArticle

Nutritional and Metabolic Consequences of Camelina Seed Oil Compared to Flaxseed Oil in a Rat Diet

by Reshma Susan Babu and Adam Jurgoński

Molecules 2025, 30(13), 2738; https://doi.org/10.3390/molecules30132738 (registering DOI) - 25 Jun 2025

Abstract

Camelina seeds are rich in α-linolenic acid (ALA), but also contain small amounts of erucic acid, which is considered toxic to laboratory rats. This experiment compares the dietary inclusion of camelina oil to that of flaxseed oil, a well-known source of ALA, and [...] Read more.

Camelina seeds are rich in α-linolenic acid (ALA), but also contain small amounts of erucic acid, which is considered toxic to laboratory rats. This experiment compares the dietary inclusion of camelina oil to that of flaxseed oil, a well-known source of ALA, and evaluates their effects on the nutritional and metabolic status of growing rats. The oils were chemically analyzed and incorporated into a semi-purified diet for 4 weeks. The experiment was divided into 3 groups: PO (control-fed palm oil with a trace of ALA), FO (comparative-fed flaxseed oil), and CO (experimental-fed camelina seed oil). Both CO and FO showed a higher percentage of lean body mass, greater lean mass gain, and a lower fat percentage compared to PO. Similar to the body composition, the blood lipid profile also improved in CO and FO, with higher HDL cholesterol and lower triglyceride levels, which was associated with upregulation of the peroxisome proliferator-activated receptor γ gene. However, in FO and CO, higher plasma liver enzyme activity and malondialdehyde concentrations were observed in the heart and liver. The results suggest that camelina oil has a similarly beneficial impact on the metabolic processes of the growing body as flaxseed oil, while also indicating a potential for increased organ-specific lipid peroxidation and hepatic burden when consumed in excess. Full article

(This article belongs to the Special Issue Food Bioactive Components in Functional Foods and Nutraceuticals)

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26 pages, 1072 KiB

Open AccessArticle

Selective Air Oxidation of Bis- and Trisphosphines Adsorbed on Activated Carbon Surfaces

by Ehsan Shakeri, John C. Hoefler and Janet Blümel

Molecules 2025, 30(13), 2737; https://doi.org/10.3390/molecules30132737 - 25 Jun 2025

Abstract

Bis- and trisphosphines incorporating methylene and aryl spacers readily adsorb on the surface of porous activated carbon (AC). The adsorption can be performed in the absence of solvents, even when the phosphines have high melting points, or from solutions. The diverse phosphines Ph [...] Read more.

Bis- and trisphosphines incorporating methylene and aryl spacers readily adsorb on the surface of porous activated carbon (AC). The adsorption can be performed in the absence of solvents, even when the phosphines have high melting points, or from solutions. The diverse phosphines Ph₂PCH₂PPh₂ (dppm), Ph₂P(CH₂)₂PPh₂ (dppe), Ph₂P(CH₂)₃PPh₂ (dppp), Ph₂P(p-C₆H₄)PPh₂ (dppbz), and (Ph₂PCH₂)₃CCH₃ (tdme) were adsorbed in submonolayers on AC. The adsorbed phosphines were studied by ³¹P MAS (magic angle spinning) NMR spectroscopy, and their mobilities on the surface were confirmed by determining the ³¹P T₁ relaxation times. All phosphine groups of each bis- and trisphosphine molecule are in contact with the surface, and the molecules exhibit translational mobility as one unit. All phosphines used here are air-stable. Once a submonolayer is created on the AC surface, oxygen from the air is co-adsorbed and transforms all phosphines quantitatively into phosphine oxides at room temperature. The oxidation proceeds in a consecutive manner with the oxidation of one phosphine group after another until the fully oxidized species are formed. Studies of the kinetics are based on integrating the signals in the solution ³¹P NMR spectra. High temperatures and low surface coverages increase the speed of the oxidation, while light and acid have no impact. The oxidation is fast and complete within one hour for 10% surface coverage at room temperature. In order to study the mechanism and slow down the oxidation, a higher surface coverage of 40% was applied. No unwanted P(V) side products or water adducts were observed. The clean phosphine oxides could be recovered in high yields by washing them off of the AC surface. The oxidation is based on radical activation of O₂ on the AC surface due to delocalized electrons on the AC surface. This is corroborated by the result that AIBN-derived radicals enable the air oxidation of PPh₃ in solution at 65 °C. When the air-stable complex (CO)₂Ni(PPh₃)₂is applied to the AC surface and exposed to the air, OPPh₃ forms quantitatively. The new surface-assisted air oxidation of phosphines adsorbed on AC renders expensive and hazardous oxidizers obsolete and opens a synthetic pathway to the selective mono-oxidation of bis- and trisphosphines. Full article

(This article belongs to the Section Inorganic Chemistry)

32 pages, 6041 KiB

Open AccessArticle

Glucagon and Glucose Availability Influence Metabolic Heterogeneity and Malignancy in Pancreatic Neuroendocrine Tumour (pNET) Cells: Novel Routes for Therapeutic Targeting

by Bárbara Ferreira, Isabel Lemos, Cindy Mendes, Beatriz Chumbinho, Fernanda Silva, Daniela Pereira, Emanuel Vigia, Luís G. Gonçalves, António Figueiredo, Daniela Cavaco and Jacinta Serpa

Molecules 2025, 30(13), 2736; https://doi.org/10.3390/molecules30132736 - 25 Jun 2025

Abstract

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour [...] Read more.

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article

(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)

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22 pages, 2199 KiB

Open AccessArticle

Antifungal Activity of 5-Fluorouridine Against Candida albicans and Candida parapsilosis Based on Virulence Reduction

by Ewa Lenarczyk, Damian Oleksiak and Monika Janeczko

Molecules 2025, 30(13), 2735; https://doi.org/10.3390/molecules30132735 - 25 Jun 2025

Abstract

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against Candida species. We evaluated the responses of nine reference species of Candida spp. and one hundred clinical isolates of C. albicans to 5-FUrd using the broth microdilution [...] Read more.

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against Candida species. We evaluated the responses of nine reference species of Candida spp. and one hundred clinical isolates of C. albicans to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive Candida species, C. albicans and C. parapsilosis. The frequency of spontaneous mutations occurring in these two Candida species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in C. albicans and C. parapsilosis cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10⁻⁵ to 1.2 × 10⁻⁴ per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti-Candida agent. Full article

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20 pages, 5045 KiB

Open AccessArticle

Sustainable Production and Antioxidant Activity of Bacterial Xanthan Gum

by Ilona Jonuškienė, Erika Davicijonaitė, Monika Vaškevičiūtė, Ihsan Kala, Rima Stankevičienė, Kristina Kantminienė and Ingrida Tumosienė

Molecules 2025, 30(13), 2734; https://doi.org/10.3390/molecules30132734 - 25 Jun 2025

Abstract

One of the world’s most sustainable solutions is to replace fossil-based polymers with biopolymers. The production of xanthan gum can be optimized using various renewable and cost-effective raw materials, which is a key focus in industrial biotechnology. Xanthan gum is a bioengineered thickening, [...] Read more.

One of the world’s most sustainable solutions is to replace fossil-based polymers with biopolymers. The production of xanthan gum can be optimized using various renewable and cost-effective raw materials, which is a key focus in industrial biotechnology. Xanthan gum is a bioengineered thickening, stabilizing, and emulsifying agent. It has unique properties for use in many industries (food, biotechnology, petrochemicals, agricultural, cosmetics, wastewater treatment) and medical applications. It is tasteless, environmentally safe, non-toxic, and biodegradable. The biotechnological production of xanthan gum depends on several factors: bacterial strain development, culture medium preparation, carbon sources, fermentation parameters and modes, pH, temperature, recovery, purification, and quality control regulations. Bio-innovative strategies have been developed to optimize the production of xanthan gum. A variety of carbon and nitrogen sources, as well as alternative renewable sources, have been used in the production of xanthan gum. The aim of the present study was to optimize the xanthan gum yield using Xanthomonas campestris bacteria and different carbon (D-glucose, D-sorbitol, lactose, sucrose, D-mannitol, D-fructose, erythritol, coconut palm sugar, L-arabinose, unrefined cane sugar), various nitrogen (bacterial peptone, casein peptone, L-glutamic acid, L-arginine, L-methionine, L-tryptophan, malt extract, meat extract, L-phenylalanine, soy peptone) and alternative carbon (orange peels, tangerine peels, lemon peels, avocado peels, melon peels, apple peels, cellulose, xylose, xylitol) sources. The xanthan gum samples were analyzed using antioxidant methods. Our study showed that using L-glutamic acid as the carbon source for 72 h of bacterial fermentation of Xanthomonas campestris resulted in the highest xanthan gum yield: 32.34 g/L. However, using renewable resources, we achieved a very high concentration of xanthan gum in just 24 h of fermentation. According to the reducing power and DPPH methods, the highest antioxidant activities were measured for xanthan gum whose biosynthesis was based on renewable resources. Xanthan gum structures have been verified by FT-IR and ¹H NMR analysis. The sustainable biotechnology study has the advantage of increasing the sustainable production of xanthan gum by using renewable alternative resources compared to other production processes. Xanthan gum continues to be a valuable biopolymer with a wide range of industrial applications while promoting environmentally friendly production practices. Full article

(This article belongs to the Special Issue Natural Products with Pharmaceutical Activities)

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14 pages, 2161 KiB

Open AccessArticle

Observation of Electroplating in a Lithium-Metal Battery Model Using Magnetic Resonance Microscopy

by Rok Peklar, Urša Mikac and Igor Serša

Molecules 2025, 30(13), 2733; https://doi.org/10.3390/molecules30132733 - 25 Jun 2025

Abstract

Accurate imaging methods are important for understanding electrodeposition phenomena in metal batteries. Among the suitable imaging methods for this task is magnetic resonance imaging (MRI), which is a very powerful radiological diagnostic method. In this study, MR microscopy was used to image electroplating [...] Read more.

Accurate imaging methods are important for understanding electrodeposition phenomena in metal batteries. Among the suitable imaging methods for this task is magnetic resonance imaging (MRI), which is a very powerful radiological diagnostic method. In this study, MR microscopy was used to image electroplating in a lithium symmetric cell, which was used as a model for a lithium-metal battery. Lithium electrodeposition in this cell was studied by sequential 3D ¹H MRI of 1 M LiPF₆ in EC/DMC electrolyte under different charging conditions, which resulted in different dynamics of the amount of electroplated lithium and its structure. The acquired images depicted the electrolyte distribution, so that the images of deposited lithium that did not give a detectable signal corresponded to the negatives of these images. With this indirect MRI, phenomena such as the transition from a mossy to a dendritic structure at Sand’s time, the growth of whiskers, the growth of dendrites with arborescent structure, the formation of dead lithium, and the formation of gas due to electrolyte decomposition were observed. In addition, the effect of charge and discharge cycles on electrodeposition was also studied. It was found that it is difficult to correctly predict the occurrence of these phenomena based on charging conditions alone, as seemingly identical conditions resulted in different results. Full article

(This article belongs to the Special Issue Advanced Magnetic Resonance Methods in Materials Chemistry Analysis)

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21 pages, 1902 KiB

Open AccessArticle

Intramolecular Versus Intermolecular Bonding in Drug Gemcitabine and Nucleobases: A Computational Study

by Natarajan Sathiyamoorthy Venkataramanan, Ambigapathy Suvitha and Ryoji Sahara

Molecules 2025, 30(13), 2732; https://doi.org/10.3390/molecules30132732 - 25 Jun 2025

Abstract

The adsorption of the drug gemcitabine on nucleobases was investigated using a dispersion-corrected density functional theory (DFT) study. The planar structure of complexes is more stable than those with stacked and buckle-angled configurations. The complexes were found to possess at least two intermolecular [...] Read more.

The adsorption of the drug gemcitabine on nucleobases was investigated using a dispersion-corrected density functional theory (DFT) study. The planar structure of complexes is more stable than those with stacked and buckle-angled configurations. The complexes were found to possess at least two intermolecular hydrogen bonds. The binding energy and interaction energy are both negative, with the highest values observed for the gemcitabine–guanine and the lowest in the gemcitabine–thymine complex. The complex formation was found to be an enthalpy-driven process. Pyrimidine nucleobases have a lower enthalpy of formation than purine nucleobases. The computed HOMA and NICS values on the gemcitabine–nucleobase complexes show a substantial increase compared to the pristine nucleobases. An MESP analysis of the complexes shows a directional interaction and electron density shift between the gemcitabine and the nucleobases. A QTAIM analysis indicates that the intermolecular hydrogen bonds have a partial covalent character. The computed bond energy demonstrates that intermolecular NH⋅⋅⋅N bonds are more potent than other bonds. An energy decomposition analysis using the DLPNO−CCSD(T) method indicates that the complexes exhibit a substantial electrostatic attraction, and dispersion contributes the least towards the system stability. The intermolecular bonds are stronger than the intramolecular bonds in the drug–nucleobase complexes. The strength of intramolecular bonds is determined by the deformation of the gemcitabine ring during the complex formation. Full article

(This article belongs to the Special Issue Organic Molecules in Drug Discovery and Development)

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22 pages, 2415 KiB

Open AccessArticle

From Tradition to Innovation: The Role of Sea Fennel in Shaping Kimchi’s Microbial, Chemical, and Sensory Profiles

by Maryem Kraouia, Maoloni Antonietta, Federica Cardinali, Vesna Milanović, Cristiana Garofalo, Andrea Osimani, Antonio Raffo, Valentina Melini, Nicoletta Nardo, Irene Baiamonte, Lucia Aquilanti and Giorgia Rampanti

Molecules 2025, 30(13), 2731; https://doi.org/10.3390/molecules30132731 - 25 Jun 2025

Abstract

Kimchi, a traditional fermented product made primarily with Chinese cabbage, develops its characteristic flavor through microbial activity and a variety of ingredients. This study explores the incorporation of sea fennel (Crithmum maritimum L.), a halophytic plant rich in bioactive compounds and known [...] Read more.

Kimchi, a traditional fermented product made primarily with Chinese cabbage, develops its characteristic flavor through microbial activity and a variety of ingredients. This study explores the incorporation of sea fennel (Crithmum maritimum L.), a halophytic plant rich in bioactive compounds and known for its distinctive aroma, into kimchi. Two fermentation methods were compared: spontaneous fermentation and fermentation using a defined starter culture of four lactic acid bacteria strains. Fermentation was conducted at 4 °C for 26 days, with samples monitored for up to 150 days. Parameters analyzed included pH, titratable acidity, microbial counts, organic acid concentrations, volatile organic compounds (VOCs), and sensory attributes. In the early stages, notable differences in acidity, microbial populations, and VOCs were observed between the two methods, but these differences diminished over time. Sensory analysis indicated similar overall characteristics for both prototypes, although the sea fennel’s aroma and fibrous texture remained perceptible at day 150. VOCs analysis revealed that the fermentation time significantly affected the composition of key aroma compounds, contributing to the final sensory profile. Sea fennel played a key role in shaping the VOC profile and imparting a distinctive aromatic quality. Both fermentation methods led to similar enhancements in flavor and product quality. These findings support the use of sea fennel as an aromatic ingredient in fermented vegetables and highlight the importance of fermentation optimization. Full article

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21 pages, 599 KiB

Open AccessArticle

Development and Validation of a LC-QTOF-MS/MS Method to Assess the Phenolic Profile of Pulse Flours

by Achilleas Panagiotis Zalidis, Natasa P. Kalogiouri, Ioannis Mourtzinos, Dimitris Sarris and Konstantinos Gkatzionis

Molecules 2025, 30(13), 2730; https://doi.org/10.3390/molecules30132730 - 25 Jun 2025

Abstract

Functional flours, defined as flours enriched with health-promoting compounds such as phenolics, fibers, or proteins, are gaining attention as wheat-free alternatives due to the nutritional limitations of wheat flour. This study introduces a novel liquid chromatographic time-of-flight tandem mass spectrometric method (LC-QTOF-MS/MS) to [...] Read more.

Functional flours, defined as flours enriched with health-promoting compounds such as phenolics, fibers, or proteins, are gaining attention as wheat-free alternatives due to the nutritional limitations of wheat flour. This study introduces a novel liquid chromatographic time-of-flight tandem mass spectrometric method (LC-QTOF-MS/MS) to characterize the phenolic profiles of functional flours from different origins and evaluate their potential as flour substitutes in food products. The proposed method was validated and the limits of quantification (LOQs) were calculated over the ranges 0.1–1.0 mg/kg. Calculated recoveries were as low as 82.4%. Repeatability and reproducibility were expressed as intra-day (n = 6) and inter-day (n = 4 × 3) measurements and were lower than 8.1 and 10.9%, respectively. Target and suspect screening findings underscore the potential of pulse flours as nutritionally enriched ingredients for functional food development. Full article

(This article belongs to the Special Issue Unveiling the Applications of Bioactive Compounds in Functional Foods for Optimal Human Health)

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17 pages, 2711 KiB

Open AccessArticle

Heterojunction-Engineered g-C₃N₄/TiO₂ Nanocomposites with Superior Bilirubin Removal Efficiency for Enhanced Hemoperfusion Therapy

by Lingdong Meng, Shouxuan Tao, Liyao Wang, Yu Cao, Jianhua Hou and Chengyin Wang

Molecules 2025, 30(13), 2729; https://doi.org/10.3390/molecules30132729 - 25 Jun 2025

Abstract

The g-C₃N₄/TiO₂ intercalation composite material was successfully synthesized and used as the adsorbent in the hemoperfusion device. Then, the cytotoxicity and hemolysis rate were studied. The experimental results proved that g-C₃N₄/TiO₂ was non-toxic [...] Read more.

The g-C₃N₄/TiO₂ intercalation composite material was successfully synthesized and used as the adsorbent in the hemoperfusion device. Then, the cytotoxicity and hemolysis rate were studied. The experimental results proved that g-C₃N₄/TiO₂ was non-toxic to cells and would not cause hemolysis. The adsorption and removal performance of the composite material for bilirubin (BR) was explored as well. The maximum adsorption capacity for BR was 850 mg·g⁻¹. Compared with the chemical hemoperfusion adsorbent coconut shell activated carbon (AC), the g-C₃N₄/TiO₂ material presented excellent adsorption performance. Furthermore, SEM, infrared spectroscopy, XPS and other characterizations results indicated that g-C₃N₄/TiO₂ has an effective adsorption effect on bilirubin, and the main adsorption mechanism is chemical adsorption. This study demonstrates that g-C₃N₄/TiO₂ may be a potential adsorbent for hemoperfusion in the treatment of hyperbilirubinemia. Full article

(This article belongs to the Section Medicinal Chemistry)

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19 pages, 3395 KiB

Open AccessArticle

Identification and Characterization of Novel Inhibitors of Human Poly(ADP-Ribose) Polymerase-1

by Ibrahim Morgan, Robert Rennert, Robert Berger, Ahmed Hassanin, Mehdi D. Davari, Daniela Eisenschmidt-Bönn and Ludger A. Wessjohann

Molecules 2025, 30(13), 2728; https://doi.org/10.3390/molecules30132728 - 25 Jun 2025

Abstract

Poly(ADP-ribose) polymerases (PARP) are a family of enzymes that were proven to play an essential role in the initiation and activation of DNA repair processes in the case of DNA single-strand breaks. The inhibition of PARP enzymes might be a promising option for [...] Read more.

Poly(ADP-ribose) polymerases (PARP) are a family of enzymes that were proven to play an essential role in the initiation and activation of DNA repair processes in the case of DNA single-strand breaks. The inhibition of PARP enzymes might be a promising option for the treatment of several challenging types of cancers, including triple-negative breast cancer (TNBC) and non-small cell lung carcinoma (NSCLC). This study utilizes several techniques to screen the compound collection of the Leibniz Institute of Plant Biochemistry (IPB) to identify novel hPARP-1 inhibitors. First, an in silico pharmacophore-based docking study was conducted to virtually screen compounds with potential inhibitory effects. To evaluate these compounds in vitro, a cell-free enzyme assay was developed, optimized, and employed to identify hPARP-1 inhibitors, resulting in the discovery of two novel scaffolds represented by compounds 54 and 57, with the latter being the most active one from the compound library. Furthermore, fluorescence microscopy and synergism assays were performed to investigate the cellular and nuclear pathways of hPARP-1 inhibitor 57 and its potential synergistic effect with the DNA-damaging agent temozolomide. The findings suggest that the compound requires further lead optimization to enhance its ability to target the nuclear PARP enzyme effectively. Nonetheless, this new scaffold demonstrated a five-fold higher PARP inhibitory activity at the enzyme level compared to the core structure of olaparib (OLP), phthalazin-1(2H)-one. Full article

(This article belongs to the Topic New Compounds Discovery and Development in Medicine — Advances in Research on Potential Therapeutic Agents and Drug Candidates, 2nd Edition)

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20 pages, 2332 KiB

Open AccessArticle

Photophysical Properties and Protein Binding Studies of Piperazine-Substituted Anthracene-BODIPY Dyads for Antimicrobial Photodynamic Therapy

by Stephen O’Sullivan, Leila Tabrizi, Kaja Turzańska, Ian P. Clark, Deirdre Fitzgerald-Hughes and Mary T. Pryce

Molecules 2025, 30(13), 2727; https://doi.org/10.3390/molecules30132727 - 25 Jun 2025

Abstract

This work presents the synthesis, characterisation, photophysical properties, time-resolved spectroscopic behaviour, and biological evaluation of two structurally distinct heavy-atom-free BODIPY-anthracene dyads (BDP-1) and the newly designed 2,6-bis[1-(tert-butyl) 4-(prop-2-yn-1-yl) piperazine-1,4-dicarboxylate] BODIPY-anthracene (BDP-2), incorporating 2,6-alkynyl-piperazine substituents for potential application in antimicrobial [...] Read more.

This work presents the synthesis, characterisation, photophysical properties, time-resolved spectroscopic behaviour, and biological evaluation of two structurally distinct heavy-atom-free BODIPY-anthracene dyads (BDP-1) and the newly designed 2,6-bis[1-(tert-butyl) 4-(prop-2-yn-1-yl) piperazine-1,4-dicarboxylate] BODIPY-anthracene (BDP-2), incorporating 2,6-alkynyl-piperazine substituents for potential application in antimicrobial photodynamic therapy. BDP-1 exhibits absorption and emission maxima at 507 nm and 516 nm, respectively, with a Stokes shift of 344 cm⁻¹ in dichloromethane (DCM), characteristic of unsubstituted BODIPYs. In contrast, BDP-2 undergoes a red-shift in the absorption maximum to 552 nm (Stokes shift of 633 cm⁻¹), which is attributed to the extended conjugation from the introduction of the alkyne groups. Time-resolved infrared spectroscopy confirmed efficient spin-orbit charge transfer intersystem crossing, and nanosecond transient absorption studies confirmed the formation of a long-lived triplet state for BDP-2 (up to 138 µs in MeCN). A binding constant (K_b) of 9.6 × 10⁴ M⁻¹ was obtained for BDP-2 when titrated with bovine serum albumin (BSA), which is higher than comparable BODIPY derivatives. BDP-2 displayed improved hemocompatibility compared to BDP-1 (<5% haemolysis of human erythrocytes up to 200 μg·mL⁻¹). Antimicrobial activity of BDP-1 and BDP-2 was most potent when irradiated at 370 nm compared to the other wavelengths employed. However, BDP-2 did not retain the potent (6 log) and rapid (within 15 min) eradication of Staphylococcus aureus achieved by BDP-1 under irradiation at 370 nm. These findings demonstrate the rational design of BDP-2 as a biocompatible, and heavy-atom-free BODIPY offering promise for targeted antimicrobial photodynamic therapeutic applications. Full article

(This article belongs to the Special Issue BODIPYs: State of the Art and Future Perspectives)

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33 pages, 2663 KiB

Open AccessReview

Grape Winemaking By-Products: Current Valorization Strategies and Their Value as Source of Tannins with Applications in Food and Feed

by Javier Echave, Antía G. Pereira, Ana O. S. Jorge, Paula Barciela, Rafael Nogueira-Marques, Ezgi N. Yuksek, María B. P. P. Oliveira, Lillian Barros and M. A. Prieto

Molecules 2025, 30(13), 2726; https://doi.org/10.3390/molecules30132726 - 25 Jun 2025

Abstract

Grape (Vitis vinifera L.) is one of the most extensively cultivated crops in temperate climates, with its primary fate being wine production, which is paired with a great generation of grape pomace (GP). GP contains a plethora of antioxidant phenolic compounds, being [...] Read more.

Grape (Vitis vinifera L.) is one of the most extensively cultivated crops in temperate climates, with its primary fate being wine production, which is paired with a great generation of grape pomace (GP). GP contains a plethora of antioxidant phenolic compounds, being well-known for its high content of various tannins, liable for the astringency of this fruit. Winemaking produces a great mass of by-products that are rich in tannins. Grape seed (GSd) and pulp waste, as well as leaves and stems (GSt), are rich in condensed tannins (CTs), while its skin (GSk) contains more flavonols and phenolic acids. CTs are polymers of flavan-3-ols, and their antioxidant and anti-inflammatory properties are well-accounted for, being the subject of extensive research for various applications. CTs from the diverse fractions of grapefruit and grapevine share similar structures given their composition but diverge in their degree of polymerization, which can modulate their chemical interactions and may be present at around 30 to 80 mg/g, depending on the grape fraction. Thus, this prominent agroindustrial by-product, which is usually managed as raw animal feed or further fermented for liquor production, can be valorized as a source of tannins with high added value. The present review addresses current knowledge on tannin diversity in grapefruit and grapevine by-products, assessing the differences in composition, quantity, and degree of polymerization. Current knowledge of their reported bioactivities will be discussed, linking them to their current and potential applications in food and feed. Full article

(This article belongs to the Special Issue Recent Advances in the Valorization of Food, Agricultural By-Products and Waste, 2nd Edition)

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14 pages, 2090 KiB

Open AccessArticle

A Carbon Nanofiber Electrochemical Sensor Made of FeMn@C for the Rapid Detection of Tert-Butyl Hydroquinone in Edible Oil

by Yan Xiao, Yi Zhang, Zhigui He, Liwen Zhang, Tongfei Wang, Tingfan Tang, Jiaxing Chen and Hao Cheng

Molecules 2025, 30(13), 2725; https://doi.org/10.3390/molecules30132725 - 25 Jun 2025

Abstract

Overuse of tert-butylhydroquinone (TBHQ) as a food antioxidant has the potential to pollute the environment and threaten human health. Therefore, it is imperative to develop precise and rapid methods to detect TBHQ in food products. In this study, Fe- and Mn-doped Prussian blue [...] Read more.

Overuse of tert-butylhydroquinone (TBHQ) as a food antioxidant has the potential to pollute the environment and threaten human health. Therefore, it is imperative to develop precise and rapid methods to detect TBHQ in food products. In this study, Fe- and Mn-doped Prussian blue analogs (FeMn-PBAs) were prepared by co-precipitation, FeMn-PBAs/PAN was prepared by electrostatic spinning, and a novel FeMn@C/CNFs composite was prepared by carbonization in nitrogen. Bimetallic FeMn doping has been shown to reduce vacancy defects and enhance the structural stability of PBA. Furthermore, electrostatic spinning has been demonstrated to reduce the agglomeration of PBA nanoparticles, which are electrode-modifying materials with high stability and good electrical conductivity. The morphological and structural characteristics of the FeMn@C/CNF composites were examined using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The electrochemical behavior of tert-butyl hydroquinone in FeMn@C/CNFs was studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronocoulometry (CC). The results demonstrate that the sensor exhibits excellent repeatability, reproducibility, and anti-interference capabilities. The prepared electrochemical sensor can be effectively utilized for the detection of TBHQ in food samples such as soybean and peanut oil samples, proving its strong potential for practical applications. Full article

(This article belongs to the Special Issue Advances in Fluorescence-Based Food Analytical Methods)

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2 pages, 351 KiB

Open AccessCorrection

Correction: Nakano et al. Bioactive Evaluation of Ursane-Type Pentacyclic Triterpenoids: β-Boswellic Acid Interferes with the Glycosylation and Transport of Intercellular Adhesion Molecule-1 in Human Lung Adenocarcinoma A549 Cells. Molecules 2022, 27, 3073

by Kaori Nakano, Saki Sasaki and Takao Kataoka

Molecules 2025, 30(13), 2724; https://doi.org/10.3390/molecules30132724 - 25 Jun 2025

Abstract

In the original publication [...] Full article

(This article belongs to the Section Natural Products Chemistry)

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19 pages, 2467 KiB

Open AccessArticle

The Impact of Dietary Habits and Maternal Body Composition on Human Milk Microbiota—Polish Pilot Study

by Agnieszka Bzikowska-Jura, Anna Koryszewska-Bagińska, Małgorzata Konieczna, Jan Gawor, Robert Gromadka, Aleksandra Wesołowska and Gabriela Olędzka

Molecules 2025, 30(13), 2723; https://doi.org/10.3390/molecules30132723 - 25 Jun 2025

Abstract

Human milk (HM) is a complex biological fluid that plays a significant role in infant health, influenced by maternal dietary habits and body composition. This study aimed to explore how maternal diet and nutritional status affect the microbial composition of HM. In this [...] Read more.

Human milk (HM) is a complex biological fluid that plays a significant role in infant health, influenced by maternal dietary habits and body composition. This study aimed to explore how maternal diet and nutritional status affect the microbial composition of HM. In this pilot study, 15 mothers were recruited from a maternity ward and assessed for dietary habits through a semi-structured food frequency questionnaire and a 3-day dietary record. Maternal body composition was evaluated using bioelectrical impedance analysis. HM samples were collected for microbiota analysis, focusing on the diversity and composition of bacterial communities via 16S rRNA sequencing. The study identified that maternal nutrient intake significantly correlated with the composition of HM microbiota. Specifically, Firmicutes abundance showed positive correlations with animal protein (τ = 0.39; p = 0.043), total carbohydrates (τ = 0.39; p = 0.043), and vitamin A (τ = 0.429; p = 0.026). Bacteroidota was positively correlated with retinol (τ = 0.39; p = 0.043). Higher consumption of dietary fiber (>24 g/day) did not yield significant differences in bacterial composition compared to lower intake (<24 g/day) (p = 0.8977). Additionally, no significant differences were found in overall bacterial abundance across different maternal characteristics such as age, mode of delivery, or breastfeeding type. This study underscores the importance of maternal diet in shaping the HM microbiota, which may have implications for infant health. Dietary modifications during lactation could be a strategic approach to promote beneficial microbial colonization in HM. Further research is warranted to confirm these findings and explore the underlying mechanisms. Full article

(This article belongs to the Special Issue Research on Bioactive Compounds in Milk)

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