Molecules

15 pages, 2979 KiB

Open AccessArticle

A Metabolomics Exploration of Young Lotus Seeds Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging

by Ying Chen, Xiaomeng Xu and Chunping Tang

Molecules 2025, 30(15), 3242; https://doi.org/10.3390/molecules30153242 (registering DOI) - 1 Aug 2025

Abstract

Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. [...] Read more.

Lotus (Nelumbo nucifera Gaertn.) is a quintessential medicinal and edible plant, exhibiting marked differences in therapeutic effects among its various parts. The lotus seed constitutes a key component of this plant. Notably, the entire seed and the plumule display distinct medicinal properties. To investigate the “homologous plants with different effects” phenomenon in traditional Chinese medicine, this study established a Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) method. This study employed immature lotus seeds as the experimental material, diverging from the mature seeds conventionally used. Conductive double-sided tape was employed for sample preparation, and complete longitudinal sections of the seeds were obtained, followed by MALDI-MSI analysis to identify and visualize the spatial distribution of characteristic secondary metabolites within the entire seeds. The results unveiled the diversity of metabolites in lotus seeds and their differential distribution across tissues, with pronounced distinctions in the plumule. A total of 152 metabolites spanning 13 categories were identified in lotus seeds, with 134, 89, 51, and 98 metabolites discerned in the pericarp, seed coat, cotyledon, and plumule, respectively. Strikingly, young lotus seeds were devoid of liensinine/isoliensinine and neferine, the dominant alkaloids of mature lotus seed plumule, revealing an early-stage alkaloid profile that sharply contrasts with the well-documented abundance found in mature seeds and has rarely been reported. We further propose a biosynthetic pathway to explain the presence of the detected benzylisoquinoline and the absence of the undetected bisbenzylisoquinoline alkaloids in this study. These findings present the first comprehensive metabolic atlas of immature lotus seeds, systematically exposing the pronounced chemical divergence from their mature counterparts, and thus lays a metabolomic foundation for dissecting the spatiotemporal mechanisms underlying the nutritional and medicinal value of lotus seeds. Full article

(This article belongs to the Special Issue New Insights into Bioactive Compounds from Natural Sources—Second Edition)

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18 pages, 695 KiB

Open AccessReview

Macromycete Edible Fungi as a Functional Poultry Feed Additive: Influence on Health, Welfare, Eggs, and Meat Quality—Review

by Damian Duda, Klaudia Jaszcza and Emilia Bernaś

Molecules 2025, 30(15), 3241; https://doi.org/10.3390/molecules30153241 (registering DOI) - 1 Aug 2025

Abstract

Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina [...] Read more.

Over the years, macromycete fungi have been used as a source of food, part of religious rites and rituals, and as a medicinal remedy. Species with strong health-promoting potential include Hericium erinaceus, Cordyceps militaris, Ganoderma lucidum, Pleurotus ostreatus, Flammulina velutipes, and Inonotus obliquus. These species contain many bioactive compounds, including β-glucans, endo- and exogenous amino acids, polyphenols, terpenoids, sterols, B vitamins, minerals, and lovastatin. The level of some biologically active substances is species-specific, e.g., hericenones and erinacines, which have neuroprotective properties, and supporting the production of nerve growth factor in the brain for Hericium erinaceus. Due to their high health-promoting potential, mushrooms and substances isolated from them have found applications in livestock nutrition, improving their welfare and productivity. This phenomenon may be of particular importance in the nutrition of laying hens and broiler chickens, where an increase in pathogen resistance to antibiotics has been observed in recent years. Gallus gallus domesticus is a key farm animal for meat and egg production, so the search for new compounds to support bird health is important for food safety. Studies conducted to date indicate that feed supplementation with mushrooms has a beneficial effect on, among other things, bird weight gain; bone mineralisation; and meat and egg quality, including the lipid profile and protein content and shell thickness, and promotes the development of beneficial microbiota, thereby increasing immunity. Full article

15 pages, 1363 KiB

Open AccessArticle

Evaluation of a Rhenium(I) Complex and Its Pyridostatin-Containing Chelator as Radiosensitizers for Chemoradiotherapy

by António Paulo, Sofia Cardoso, Edgar Mendes, Elisa Palma, Paula Raposinho and Ana Belchior

Molecules 2025, 30(15), 3240; https://doi.org/10.3390/molecules30153240 (registering DOI) - 1 Aug 2025

Abstract

The use of radiosensitizers is a beneficial approach in cancer radiotherapy treatment. However, the enhancement of radiation effects on cancer cells by radiosensitizers involves several different mechanisms, reflecting the chemical nature of the radiosensitizer. G-quadruplex (G4) DNA ligands have emerged in recent years [...] Read more.

The use of radiosensitizers is a beneficial approach in cancer radiotherapy treatment. However, the enhancement of radiation effects on cancer cells by radiosensitizers involves several different mechanisms, reflecting the chemical nature of the radiosensitizer. G-quadruplex (G4) DNA ligands have emerged in recent years as a potential new class of radiosensitizers binding to specific DNA sequences. Recently, we have shown that the Re(I) tricarbonyl complex PDF-Pz-Re and its pyrazolyl-diamine chelator PDF-Pz, carrying a N-methylated pyridostatin (PDF) derivative, act as G4 binders of various G4-forming DNA and RNA sequences. As described in this contribution, these features prompted us to evaluate PDF-Pz-Re and PDF-Pz as radiosensitizers of prostate cancer PC3 cells submitted to concomitant treatment with Co-60 radiation. The compound RHPS4 was also tested, as this G4 ligand was previously shown to exhibit strong radiosensitizing properties in other cancer cell lines. The assessment of the resulting radiobiological effects, namely through clonogenic cell survival, DNA damage, and ROS production assays, showed that PDF-Pz-Re and PDF-Pz were able to radiosensitize PC3 cells despite being less active than RHPS4. Our results corroborate that G4 DNA ligands are a class of compounds with potential interest as radiosensitizers, deserving further studies to optimize their radiosensitization activity and elucidate the mechanisms of action. Full article

(This article belongs to the Special Issue Metal-Based Drugs: Past, Present and Future, 3rd Edition)

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17 pages, 1346 KiB

Open AccessFeature PaperArticle

Incorporation and Repair of Epigenetic Intermediates as Potential Chemotherapy Agents

by Jason L. Herring, Mark L. Sowers, James W. Conrad, Linda C. Hackfeld, Bruce Chang-Gu, Rahul Dilawari and Lawrence C. Sowers

Molecules 2025, 30(15), 3239; https://doi.org/10.3390/molecules30153239 (registering DOI) - 1 Aug 2025

Abstract

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic [...] Read more.

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic reprogramming intermediates—in the U87 glioblastoma cell line. We found that two analogs, 5-hydroxymethyl-2′-deoxyuridine (5HmdU) and trifluorothymidine (TFT), are both cytotoxic and are efficiently incorporated into genomic DNA. In contrast, the 5-carboxy analogs—5-carboxy-2′-deoxyuridine (5CadU) and 5-carboxycytidine (5CadC)—showed no cytotoxicity and were not incorporated into DNA. Interestingly, 5-hydroxymethyl-2′-deoxycytidine (5HmdC) was cytotoxic but was not directly incorporated into DNA. Instead, it was deaminated into 5HmdU, which was then incorporated and likely responsible for the observed toxicity. 5HmdU is actively removed from DNA through the BER pathways. In contrast, TFT remains stably incorporated and is neither excised by BER nor does it hydrolyze into 5CadU—a known substrate for the DNA glycosylase SMUG1. We also found that N⁶-benzyladenosine (BzAdo), an inhibitor of the enzyme 2′-deoxynucleoside 5′-phosphate N-hydrolase (DNPH1), enhances the cytotoxicity of 5HmdU. However, the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) does not increase the cytotoxic effect of TFT in U87 cells. Together, these findings highlight 5HmdU and TFT as promising chemotherapeutic agents for glioblastoma, each with distinct mechanisms of action and cellular processing. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues: Chemical Synthesis and Applications)

33 pages, 3259 KiB

Open AccessReview

Recent Development on the Synthesis Strategies and Mechanisms of Co₃O₄-Based Electrocatalysts for Oxygen Evolution Reaction: A Review

by Liangjuan Gao, Yifan Jia and Hongxing Jia

Molecules 2025, 30(15), 3238; https://doi.org/10.3390/molecules30153238 (registering DOI) - 1 Aug 2025

Abstract

The usage of fossil fuels has resulted in increasingly severe environmental problems, such as climate change, air pollution, water pollution, etc. Hydrogen energy is considered one of the most promising clean energies to replace fossil fuels due to its pollution-free and high-heat properties. [...] Read more.

The usage of fossil fuels has resulted in increasingly severe environmental problems, such as climate change, air pollution, water pollution, etc. Hydrogen energy is considered one of the most promising clean energies to replace fossil fuels due to its pollution-free and high-heat properties. However, the oxygen evolution reaction (OER) remains a critical challenge due to its high overpotential and slow kinetics during water electrolysis for hydrogen production. Electrocatalysts play an important role in lowering the overpotential of OER and promoting the kinetics. Co₃O₄-based electrocatalysts have emerged as promising candidates for the oxygen evolution reaction (OER) due to their favorable catalytic activity and good compatibility compared with precious metal-based electrocatalysts. This review presents a summary of the recent developments in the synthesis strategies and mechanisms of Co₃O₄-based electrocatalysts for the OER. Various synthesis strategies have been explored to control the size, morphology, and composition of Co₃O₄ nanoparticles. These strategies enable the fabrication of well-defined nanostructures with enhanced catalytic performance. Additionally, the mechanisms of OER catalysis on Co₃O₄-based electrocatalysts have been elucidated. Coordinatively unsaturated sites, synergistic effects with other elements, surface restructuring, and pH dependency have been identified as crucial factors influencing the catalytic activity. The understanding of these mechanisms provides insights into the design and optimization of Co₃O₄-based electrocatalysts for efficient OER applications. The recent advancements discussed in this review offer valuable perspectives for researchers working on the development of electrocatalysts for the OER, with the goal of achieving sustainable and efficient energy conversion and storage systems. Full article

(This article belongs to the Special Issue Emerging Multifunctional Materials for Next-Generation Energy Systems)

11 pages, 577 KiB

Open AccessArticle

New Method for the Determination of Lamotrigine in Human Saliva Using SPE-LC-DAD

by Ewelina Dziurkowska, Aleksandra Michalak, Alina Plenis and Maciej Dziurkowski

Molecules 2025, 30(15), 3237; https://doi.org/10.3390/molecules30153237 (registering DOI) - 1 Aug 2025

Abstract

(1) Background: The concentration of lamotrigine, an antiepileptic drug very often used in bipolar disorder, is most often determined in the blood, with many inconveniences. An alternative may be to use saliva as a diagnostic material for this purpose. The development of a [...] Read more.

(1) Background: The concentration of lamotrigine, an antiepileptic drug very often used in bipolar disorder, is most often determined in the blood, with many inconveniences. An alternative may be to use saliva as a diagnostic material for this purpose. The development of a method to determine lamotrigine in saliva as a biological material significantly improves patient comfort during sampling. The developed method uses solid-phase extraction for the isolation of the drug from saliva for the first time. (2) Methods: This study aimed to develop a method to determine lamotrigine in saliva using solid-phase extraction (SPE) for isolation and liquid chromatography with a diode array detector (LC-DAD) for quantitative analysis. (3) Results: The method was validated by determining its linearity in the concentration range 10–2000 ng/mL (R² > 0.99), and the intra- and inter-day precision expressed as coefficient of variation (CV%) did not exceed 15%. (4) Conclusions: The developed method was used to determine the salivary concentration of lamotrigine in patients treated with the studied compound, confirming its usefulness in bipolar disorder (BD). Full article

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33 pages, 4366 KiB

Open AccessReview

Progress and Prospects of Biomolecular Materials in Solar Photovoltaic Applications

by Anna Fricano, Filippo Tavormina, Bruno Pignataro, Valeria Vetri and Vittorio Ferrara

Molecules 2025, 30(15), 3236; https://doi.org/10.3390/molecules30153236 (registering DOI) - 1 Aug 2025

Abstract

This Review examines up-to-date advancements in the integration of biomolecules and solar energy technologies, with a particular focus on biohybrid photovoltaic systems. Biomolecules have recently garnered increasing interest as functional components in a wide range of solar cell architectures, since they offer a [...] Read more.

This Review examines up-to-date advancements in the integration of biomolecules and solar energy technologies, with a particular focus on biohybrid photovoltaic systems. Biomolecules have recently garnered increasing interest as functional components in a wide range of solar cell architectures, since they offer a huge variety of structural, optical, and electronic properties, useful to fulfill multiple roles within photovoltaic devices. These roles span from acting as light-harvesting sensitizers and charge transport mediators to serving as micro- and nanoscale structural scaffolds, rheological modifiers, and interfacial stabilizers. In this Review, a comprehensive overview of the state of the art about the integration of biomolecules across the various generations of photovoltaics is provided. The functional roles of pigments, DNA, proteins, and polysaccharides are critically reported improvements and limits associated with the use of biological molecules in optoelectronics. The molecular mechanisms underlying the interaction between biomolecules and semiconductors are also discussed as essential for a functional integration of biomolecules in solar cells. Finally, this Review shows the current state of the art, and the most significant results achieved in the use of biomolecules in solar cells, with the main scope of outlining some guidelines for future further developments in the field of biohybrid photovoltaics. Full article

(This article belongs to the Special Issue Thermal and Photocatalytic Analysis of Nanomaterials: 2nd Edition)

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18 pages, 3224 KiB

Open AccessArticle

Design of Experiments Approach for Efficient Heavy Metals Stabilization Using Metakaolin-Based Geopolymers

by Raffaele Emanuele Russo, Elisa Santoni, Martina Fattobene, Mattia Giovini, Francesco Genua, Cristina Leonelli, Isabella Lancellotti, Ana Herrero and Mario Berrettoni

Molecules 2025, 30(15), 3235; https://doi.org/10.3390/molecules30153235 (registering DOI) - 1 Aug 2025

Abstract

Alkali-activated aluminosilicate matrices are increasingly studied for their ability to stabilize hazardous metal contaminants via alkali activation at room temperature. In this study, metakaolin-based geopolymers were used to immobilize chromium and nickel salts, with systematic variation of key synthesis parameters, Na/Al molar ratio, [...] Read more.

Alkali-activated aluminosilicate matrices are increasingly studied for their ability to stabilize hazardous metal contaminants via alkali activation at room temperature. In this study, metakaolin-based geopolymers were used to immobilize chromium and nickel salts, with systematic variation of key synthesis parameters, Na/Al molar ratio, metal concentration, anion type, and alkaline solution aging time, which have not been previously studied. A Design of Experiments approach was employed to study the effect of factors on metal leaching behavior and to better understand the underlying immobilization mechanisms. The analysis revealed that higher Na/Al ratios significantly enhance geopolymerization and reduce metal release, as supported by FTIR spectral shifts and decreased shoulder intensity. Notably, aging time had an influence on chromium behavior due to its effect on early silicate network formation, which can hinder the incorporation of chromium species. All tested formulations achieved metal immobilization rates of 98.8% or higher for both chromium and nickel. Overall, this study advances our understanding of geopolymer-based heavy metal immobilization. Full article

(This article belongs to the Special Issue Green Chemistry Approaches to Analysis and Environmental Remediation)

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25 pages, 2412 KiB

Open AccessReview

Toxic Effects of the Most Common Components of Energetic Co-Crystals

by Xinying Peng, Cunzhi Li, Huan Li, Hui Deng, Xiaoqiang Lv, Ting Gao, Jiachen Shen, Bin Zhao, Zhiyong Liu and Junhong Gao

Molecules 2025, 30(15), 3234; https://doi.org/10.3390/molecules30153234 (registering DOI) - 1 Aug 2025

Abstract

Hexanitrohexaazaisowurtzitane (CL-20) is a high-energy-density material known for its exceptional explosive performance, but it suffers from significant safety concerns due to its high sensitivity. To mitigate this issue, researchers have explored the synthesis of CL-20-based cocrystals with other energetic materials to achieve a [...] Read more.

Hexanitrohexaazaisowurtzitane (CL-20) is a high-energy-density material known for its exceptional explosive performance, but it suffers from significant safety concerns due to its high sensitivity. To mitigate this issue, researchers have explored the synthesis of CL-20-based cocrystals with other energetic materials to achieve a balance between energy output and safety. Recent advancements in CL-20 cocrystals have focused on developing novel synthesis methods and leveraging computational design techniques to predict and optimize their physicochemical properties. However, the toxicity of CL-20 cocrystals, along with their environmental and health risks, remains a critical concern. This review systematically examines recent progress in CL-20 cocrystal energetic materials, emphasizing toxicity profiles and mechanistic insights into their components. The findings serve as a foundation for the development of safer energetic materials, thereby facilitating sustainable advancements in manufacturing technologies and industrial applications of CL-20. Full article

15 pages, 5007 KiB

Open AccessArticle

In Situ Construction of Thiazole-Linked Covalent Organic Frameworks on Cu₂O for High-Efficiency Photocatalytic Tetracycline Degradation

by Zhifang Jia, Tingxia Wang, Zhaoxia Wu, Shumaila Razzaque, Zhixiang Zhao, Jiaxuan Cai, Wenao Xie, Junli Wang, Qiang Zhao and Kewei Wang

Molecules 2025, 30(15), 3233; https://doi.org/10.3390/molecules30153233 (registering DOI) - 1 Aug 2025

Abstract

The strategic construction of heterojunctions through a simple and efficient strategy is one of the most effective means to boost the photocatalytic activity of semiconductor materials. Herein, a thiazole-linked covalent organic framework (TZ-COF) with large surface area, well-ordered pore structure, and high stability [...] Read more.

The strategic construction of heterojunctions through a simple and efficient strategy is one of the most effective means to boost the photocatalytic activity of semiconductor materials. Herein, a thiazole-linked covalent organic framework (TZ-COF) with large surface area, well-ordered pore structure, and high stability was developed. To further boost photocatalytic activity, the TZ-COF was synthesized in situ on the surface of Cu₂O through a simple multicomponent reaction, yielding an encapsulated composite material (Cu₂O@TZ-COF-18). In this composite, the outermost COF endows the material with abundant redox active sites and mass transfer channels, while the innermost Cu₂O exhibits unique photoelectric properties. Notably, the synthesized Cu₂O@TZ-COF-18 was proven to have the heterojunction structure, which can efficiently restrain the recombination of photogenerated electron–hole pairs, thereby enhancing the photocatalytic performance. The photocatalytic degradation of tetracycline demonstrated that 3-Cu₂O@TZ-COF-18 had the highest photocatalytic efficiency, with the removal rate of 96.3% within 70 min under visible light, which is better than that of pristine TZ-COF-18, Cu₂O, the physical mixture of Cu₂O and TZ-COF-18, and numerous reported COF-based composite materials. 3-Cu₂O@TZ-COF-18 retained its original crystallinity and removal efficiency after five cycles in photodegradation reaction, displaying high stability and excellent cycle performance. Full article

(This article belongs to the Special Issue Purposeful Assembly and Versatile Applications of Advanced Crystalline Frameworks)

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Graphical abstract

12 pages, 1435 KiB

Open AccessArticle

Amino Acid Analysis and Cytotoxicity Study of Iraqi Ocimum basilicum Plant

by Omar Hussein Ahmed

Molecules 2025, 30(15), 3232; https://doi.org/10.3390/molecules30153232 (registering DOI) - 1 Aug 2025

Abstract

Background: This paper deals with the detection of amino acid composition of Iraqi Ocimum basilicum (basil) leaves and evaluation of the cytotoxic effects of the plant leaf extract on human colorectal cancer cells. Methods: Leaves of Ocimum basilicum were collected from Iraq in [...] Read more.

Background: This paper deals with the detection of amino acid composition of Iraqi Ocimum basilicum (basil) leaves and evaluation of the cytotoxic effects of the plant leaf extract on human colorectal cancer cells. Methods: Leaves of Ocimum basilicum were collected from Iraq in November 2024. After drying and powdering, the plant material went through cold methanol extraction. Initial phytochemical screening was conducted to identify the presence of alkaloids, flavonoids, coumarins, and terpenoids. Amino acid analysis was completed by an amino acid analyzer with fluorescence detection. The cytotoxic effect was evaluated via the MTT assay on HRT-18 cell lines. Morphological changes were further tested using dual Propidium Iodide/Acridine Orange assay fluorescent staining. Results: Seventeen amino acids were detected in the plant extract. The extract showed dose-dependent cytotoxic effects on HRT-18 cells, with significant reduction in cell viability at concentrations of more than 25 µg/mL. Morphological alterations of membrane blebbing and cell shrinkage were observed, suggesting apoptotic activity. The IC₅₀ value confirmed strong cytotoxic potential. Conclusions: The extract of Ocimum basilicum leaf cultivated in Iraq shows a rich amino acid profile and significant cytotoxic activity against colorectal cancer cells that highlights its potential effect as a natural source of anticancer compounds. Full article

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20 pages, 6929 KiB

Open AccessArticle

Protective Effects of Sodium Copper Chlorophyllin and/or Ascorbic Acid Against Barium Chloride-Induced Oxidative Stress in Mouse Brain and Liver

by Salma Benayad, Basma Es-Sai, Yassir Laaziouez, Soufiane Rabbaa, Hicham Wahnou, Habiba Bouchab, Hicham El Attar, Bouchra Benabdelkhalek, Loubna Amahdar, Oualid Abboussi, Raphaël Emmanuel Duval, Riad El Kebbaj and Youness Limami

Molecules 2025, 30(15), 3231; https://doi.org/10.3390/molecules30153231 (registering DOI) - 1 Aug 2025

Abstract

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in [...] Read more.

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

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21 pages, 4228 KiB

Open AccessArticle

The Combined Effect of Caseinates, Native or Heat-Treated Whey Proteins, and Cryogel Formation on the Characteristics of Kefiran Films

by Nikoletta Pouliou, Eirini Chrysovalantou Paraskevaidou, Athanasios Goulas, Stylianos Exarhopoulos and Georgia Dimitreli

Molecules 2025, 30(15), 3230; https://doi.org/10.3390/molecules30153230 (registering DOI) - 1 Aug 2025

Abstract

Kefiran, the extracellular polysaccharide produced from the Generally Recognized as Safe (GRAS) bacteria in kefir grains, with its well-documented functional and health-promoting properties, constitutes a promising biopolymer with a variety of possible uses. Its compatibility with other biopolymers, such as milk proteins, and [...] Read more.

Kefiran, the extracellular polysaccharide produced from the Generally Recognized as Safe (GRAS) bacteria in kefir grains, with its well-documented functional and health-promoting properties, constitutes a promising biopolymer with a variety of possible uses. Its compatibility with other biopolymers, such as milk proteins, and its ability to form standalone cryogels allow it to be utilized for the fabrication of films with improved properties for applications in the food and biomedical–pharmaceutical industries. In the present work, the properties of kefiran films were investigated in the presence of milk proteins (sodium caseinate, native and heat-treated whey proteins, and their mixtures), alongside glycerol (as a plasticizer) and cryo-treatment of the film-forming solution prior to drying. A total of 24 kefiran films were fabricated and studied for their physical (thickness, moisture content, water solubility, color parameters and vapor adsorption), mechanical (tensile strength and elongation at break), and optical properties. Milk proteins increased film thickness, solubility and tensile strength and reduced water vapor adsorption. The hygroscopic effect of glycerol was mitigated in the presence of milk proteins and/or the application of cryo-treatment. Glycerol was the most effective at reducing the films’ opacity. Heat treatment of whey proteins proved to be the most effective in increasing film tensile strength, reducing, at the same time, the elongation at break, while sodium caseinates in combination with cryo-treatment resulted in films with high tensile strength and the highest elongation at break. Cryo-treatment, carried out in the present study through freezing followed by gradual thawing of the film-forming solution, proved to be the most effective factor in decreasing film roughness. Based on our results, proper selection of the film-forming solution composition and its treatment prior to drying can result in kefiran–glycerol films with favorable properties for particular applications. Full article

(This article belongs to the Special Issue Development of Food Packaging Materials)

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12 pages, 2241 KiB

Open AccessArticle

PDE Inhibitors and Autophagy Regulators Modulate CRE-Dependent Luciferase Activity in Neuronal Cells from the Mouse Suprachiasmatic Nucleus

by Erik Maronde and Abdelhaq Rami

Molecules 2025, 30(15), 3229; https://doi.org/10.3390/molecules30153229 (registering DOI) - 1 Aug 2025

Abstract

Background: Signaling pathways like those depending on cAMP/PKA, calcium/calmodulin/CaMK, MEK-1/MAPK or PI3K/Akt have been described to modulate suprachiasmatic nucleus (SCN) neuronal signaling via influencing transcription factors like CREB. Here, we analyzed the effect of cyclic nucleotide phosphodiesterase inhibitors and structurally similar substances commonly [...] Read more.

Background: Signaling pathways like those depending on cAMP/PKA, calcium/calmodulin/CaMK, MEK-1/MAPK or PI3K/Akt have been described to modulate suprachiasmatic nucleus (SCN) neuronal signaling via influencing transcription factors like CREB. Here, we analyzed the effect of cyclic nucleotide phosphodiesterase inhibitors and structurally similar substances commonly used as autophagy modulators on a cell line stably expressing a cyclic nucleotide element-driven luciferase reporter. Methods: We used an SCN cell line stably transfected with a CRE-luciferase reporter (SCNCRE) to evaluate signaling and vitality responses to various isoform-selective PDE inhibitors and autophagy modulators to evaluate the mechanism of action of the latter. Results: In this study the different impacts of common PDE inhibitors and autophagy modulators on CRE-luciferase activity applied alone and in combination with known CRE-luciferase activating agents showed that (1) PDE3, 4 and 5 are present in SCNCRE cells, with (2) PDE3 being the most active and (3) the autophagy inhibitor 3-Methyladenin (3-MA) displaying PDE inhibitor-like behavior. Conclusions: Experiments provide evidence that, in addition to the extracellular signaling pathways components shown before to be involved in CRE-luciferase activity regulation like cAMP analogs, adenylate cyclase activators and beta-adrenoceptor agonists, cyclic nucleotide metabolism as realized by phosphodiesterase activity, or molecule/agents influencing processes like autophagy or inflammation, modulate transcriptional CRE-dependent activity in these cells. Specifically, we provide evidence that the autophagy inhibitor 3-MA, given that PDEs are expressed, may also act as a PDE inhibitor and inducer of CRE-mediated transcriptional activity. Full article

(This article belongs to the Special Issue Exploring Bioactive Organic Compounds for Drug Discovery, 2nd Edition)

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20 pages, 3586 KiB

Open AccessArticle

Enhanced NiFe₂O₄ Catalyst Performance and Stability in Anion Exchange Membrane Water Electrolysis: Influence of Iron Content and Membrane Selection

by Khaja Wahab Ahmed, Aidan Dobson, Saeed Habibpour and Michael Fowler

Molecules 2025, 30(15), 3228; https://doi.org/10.3390/molecules30153228 (registering DOI) - 1 Aug 2025

Abstract

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were [...] Read more.

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were investigated. The NiFeO_x catalysts were synthesized with various iron content weight percentages, and at the stoichiometric ratio for nickel ferrite (NiFe₂O₄). The catalytic activity of NiFeO_x catalyst was evaluated by linear sweep voltammetry (LSV) and chronoamperometry for the oxygen evolution reaction (OER). NiFe₂O₄ showed the highest activity for the OER in a three-electrode system, with 320 mA cm⁻² at 2 V in 1 M KOH solution. NiFe₂O₄ displayed strong stability over a 600 h period at 50 mA cm⁻² in a three-electrode setup, with a degradation rate of 15 μV/h. In single-cell electrolysis using a X-37 T membrane, at 2.2 V in 1 M KOH, the NiFe₂O₄ catalyst had the highest activity of 1100 mA cm⁻² at 45 °C, which increased with the temperature to 1503 mA cm⁻² at 55 °C. The performance of various membranes was examined, and the highest performance of the tested membranes was determined to be that of the Fumatech FAA-3-50 and FAS-50 membranes, implying that membrane performance is strongly correlated with membrane conductivity. The obtained Nyquist plots and equivalent circuit analysis were used to determine cell resistances. It was found that ohmic resistance decreases with an increase in temperature from 45 °C to 55 °C, implying the positive effect of temperature on AEM electrolysis. The FAA-3-50 and FAS-50 membranes were determined to have lower activation and ohmic resistances, indicative of higher conductivity and faster membrane charge transfer. NiFe₂O₄ in an AEM water electrolyzer displayed strong stability, with a voltage degradation rate of 0.833 mV/h over the 12 h durability test. Full article

(This article belongs to the Special Issue Water Electrolysis)

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24 pages, 2572 KiB

Open AccessArticle

Hair Levels of Lead, Cadmium, Selenium, and Their Associations with Neurotoxicity and Hematological Biomarkers in Children from the Mojana Region, Colombia

by Jenny Palomares-Bolaños, Jesus Olivero-Verbel and Karina Caballero-Gallardo

Molecules 2025, 30(15), 3227; https://doi.org/10.3390/molecules30153227 (registering DOI) - 1 Aug 2025

Abstract

Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing [...] Read more.

Heavy metals are a major toxicological concern due to their adverse effects on human health, particularly in children exposed to contaminated areas. This study evaluated biomarkers of exposure in 253 children aged 6 to 12 from Magangue, Achi, and Arjona (Bolivar, Colombia), analyzing their relationship with neurotoxicity and hematological markers. The mean Pb concentrations at the study sites were 1.98 µg/g (Magangue) > 1.51 µg/g (Achi) > 1.24 µg/g (Arjona). A similar pattern was observed for Cd concentrations for Magangue (0.39 µg/g) > Achi (0.36 µg/g) > Arjona (0.14 µg/g). In contrast, Se concentrations followed a different trend for Arjona (0.29 µg/g) > Magangue (0.21 µg/g) > Achi (0.16 µg/g). The proportion of Se/Pb molar ratios > 1 was higher in Arjona (3.8%) than in Magangue (0.9%) and Achi (2.0%). For Se/Cd ratios, values > 1 were also more frequent in Arjona (70.7%), exceeding 20% in the other two locations. Significant differences were found among locations in red and white blood cell parameters and platelet indices. Neurotransmitter-related biomarkers, including serotonin, monoamine oxidase A (MAO-A), and acetylcholinesterase levels, also varied by location. Principal component analysis showed that Pb and Cd had high loadings on the same component as PLT, WBC, and RDW, and while Se loaded together with HGB, PDW, MCHC, MCH, and MCV, suggesting distinct hematological patterns associated with each element. Multiple linear regression analysis demonstrated a statistically significant inverse association between hair Pb levels and serotonin concentrations. Although MAO-A and Cd showed negative β coefficients, these associations were not statistically significant after adjustment. These findings highlight the potential impact of toxic element exposure on key hematological and neurochemical parameters in children, suggesting early biological alterations that may compromise health and neurodevelopment. Full article

(This article belongs to the Section Analytical Chemistry)

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25 pages, 1206 KiB

Open AccessArticle

Application of Protein Structure Encodings and Sequence Embeddings for Transporter Substrate Prediction

by Andreas Denger and Volkhard Helms

Molecules 2025, 30(15), 3226; https://doi.org/10.3390/molecules30153226 (registering DOI) - 1 Aug 2025

Abstract

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid [...] Read more.

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid sequence embeddings with protein language models (pLMs), highly accurate 3D structure predictions with AlphaFold 2, and structure-encoding 3Di sequences from FoldSeek, for predicting substrates of membrane transporters. We test new deep learning features derived from both sequence and structure, and compare them to the previously best-performing protein encodings, which were made up of amino acid k-mer frequencies and evolutionary information from PSSMs. Furthermore, we compare the performance of these features either using a previously developed SVM model, or with a regularized feedforward neural network (FNN). When evaluating these models on sugar and amino acid carriers in A. thaliana, as well as on three types of ion channels in human, we found that both the DL-based features and the FNN model led to a better and more consistent classification performance compared to previous methods. Direct encodings of 3D structures with Foldseek, as well as structural embeddings with ProstT5, matched the performance of state-of-the-art amino acid sequence embeddings calculated with the ProtT5-XL model when used as input for the FNN classifier. Full article

(This article belongs to the Special Issue Application of Computational Studies for Elucidation of Protein Structure and Function)

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15 pages, 2399 KiB

Open AccessReview

Cyclodextrin-Based Supramolecular Hydrogels in Tissue Engineering and Regenerative Medicine

by Jiamin Lin, Yuanyuan Chen and Xuemei Wang

Molecules 2025, 30(15), 3225; https://doi.org/10.3390/molecules30153225 (registering DOI) - 31 Jul 2025

Abstract

Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication [...] Read more.

Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication strategies for CD-based supramolecular hydrogels and their applications in tissue engineering and regenerative medicine, with focused analysis on wound healing, corneal regeneration, and bone repair. We critically analyze CD–guest molecular interaction mechanisms and innovative therapeutic implementations, highlighting the significant potential of CD hydrogels for tissue regeneration while addressing clinical translation challenges and future directions. Full article

(This article belongs to the Special Issue Cyclodextrin Chemistry and Toxicology III)

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17 pages, 7013 KiB

Open AccessArticle

A Novel HDAC6 Inhibitor Ameliorates Imiquimod-Induced Psoriasis-Like Inflammation in Mice

by Anqi Cao, Yurong Li, Yanqiao Feng, Xiaoquan Wang, Wenyu Wei, Hongyan Sun and Junmin Quan

Molecules 2025, 30(15), 3224; https://doi.org/10.3390/molecules30153224 (registering DOI) - 31 Jul 2025

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of keratinocytes and infiltration of inflammatory cells. Significant challenges remain in developing effective and safe targeted therapies for psoriasis. Here, we reported the discovery of novel cystamine derivatives for the treatment of [...] Read more.

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of keratinocytes and infiltration of inflammatory cells. Significant challenges remain in developing effective and safe targeted therapies for psoriasis. Here, we reported the discovery of novel cystamine derivatives for the treatment of psoriasis. These compounds effectively attenuated LPS-induced inflammation in vitro, and the optimal candidate CS1 ameliorated imiquimod-induced psoriasis-like inflammation in mice. Mechanistically, CS1 bound and inhibited the deacetylase HDAC6, subsequently inhibited the AKT, MAPK, and STAT3 pathways, attenuated the hyperproliferation and altered differentiation of keratinocytes and reduced the infiltration of immune cells. These findings suggest that HDAC6 may serve as a potential target for drug development in the treatment of psoriasis. Full article

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