Molecules

11 pages, 1022 KB

Open AccessArticle

Linking Phytochemical Diversity to Aflatoxin Suppression: LC-MS/MS Metabolomics of Trichilia dregeana Bark Extracts

by Martha Cebile Jobe, Babra Moyo, Ntakadzeni Edwin Madala and Mulunda Mwanza

Molecules 2026, 31(3), 578; https://doi.org/10.3390/molecules31030578 - 6 Feb 2026

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Trichilia dregeana has a rich phytochemical diversity and biological activity; however, information on its metabolomic profile and antimycotoxigenic potential is limited. This study investigated different extracts of T. dregeana bark obtained with various solvents (water, ethanol, ethyl acetate, and methanol), assessing their chemical [...] Read more.

Trichilia dregeana has a rich phytochemical diversity and biological activity; however, information on its metabolomic profile and antimycotoxigenic potential is limited. This study investigated different extracts of T. dregeana bark obtained with various solvents (water, ethanol, ethyl acetate, and methanol), assessing their chemical composition using LC-MS and their inhibitory activity against the aflatoxin produced by Aspergillus fungi. LC-MS analysis identified metabolites belonging to several secondary metabolite classes, including flavonoids, phenolic acids, lignan glycosides, cardiac glycosides, coumarins, cinnamic acids, and limonoids. Solvent polarity strongly influenced metabolite distribution, with water and methanol enriching polar antioxidant compounds, while ethanol and ethyl acetate extracted semipolar antimicrobial constituents. The antimycotoxigenic efficacy of T. dregeana bark extracts was evaluated against Aspergillus flavus in maize, rice, and flour matrices. Among the tested extracts, only the methanolic extract exhibited a statistically significant reduction in aflatoxin levels (µg/kg), while the water, ethanol, and ethyl acetate extracts showed no significant inhibition. Fungal inoculation significantly increased aflatoxin levels, with maize showing the highest contamination (673.32 µg/kg). At 50 µg/mL extract, aflatoxin concentrations were reduced to 230.39 µg/kg maize, 129.93 µg/kg rice, and 143.89 µg/kg flour, with efficacy comparable to or exceeding the commercial fungicide tenazole. Associations between solvent-dependent metabolite class distribution and aflatoxin suppression were observed; however, bioactivity was demonstrated exclusively at the crude extract level. These findings suggest that methanolic extracts of T. dregeana bark may represent a promising natural alternative to antimycotoxin agents, warranting further fractionation and mechanistic validation. Full article

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17 pages, 7642 KB

Open AccessArticle

The Synthesis, Metal Exchange, and Hyaluronate Functionalization of a Cationic Gallium-Based Thiosemicarbazone Anticancer Drug

by Ye Ning, Meng-Lin Dong, Wen-Hua Zhang and David J. Young

Molecules 2026, 31(3), 577; https://doi.org/10.3390/molecules31030577 - 6 Feb 2026

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Abstract

We herein demonstrate that the thiosemicarbazone (TSC) ligand N′-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) can coordinate with Ga³⁺ to give cationic complex [Ga(L)₂]NO₃ featuring an octahedral Ga(III) center. [Ga(L)₂]NO₃ undergoes metathesis with both Fe²⁺ and Fe³⁺ [...] Read more.

We herein demonstrate that the thiosemicarbazone (TSC) ligand N′-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) can coordinate with Ga³⁺ to give cationic complex [Ga(L)₂]NO₃ featuring an octahedral Ga(III) center. [Ga(L)₂]NO₃ undergoes metathesis with both Fe²⁺ and Fe³⁺, resulting in the formation of respective Fe²⁺- and Fe³⁺ complexes. [Ga(L)₂]NO₃ is also susceptible to anion exchange with sodium hyaluronate (NaA) to produce the nanoformulation [Ga(L)₂]A with boosted aqueous solubility and cell targeting. [Ga(L)₂]A demonstrated remarkable in vitro cytotoxicity against NCI-H82 and A549 (lung cancer), as well as KYSE-510 and Te-1 (esophageal cancer) cell lines, featuring half maximal inhibitory concentration (IC₅₀) values in the range 0.102–2.616 μmol L⁻¹. This work highlights the potential of using non-toxic and biocompatible Ga³⁺ as the central ion to prepare TSC-based nanomedicines for combating cancer. Full article

(This article belongs to the Special Issue Transition Metal Complexes with Bioactive Ligands)

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17 pages, 6468 KB

Open AccessArticle

Water-Soluble Palladium Complexes with 1,10-Phenanthroline—Synthetic Aspects, Crystal Structure, DNA-Binding and In Vitro Antibacterial Evaluation

by Marina A. Uvarova, Ilya A. Yakushev, Nina A. Kasyanenko, Natalia A. Komolkina, Noura Hilal and Igor L. Eremenko

Molecules 2026, 31(3), 576; https://doi.org/10.3390/molecules31030576 - 6 Feb 2026

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Abstract

Obtaining water-soluble palladium complexes capable of interacting with DNA is an important synthetic task in medicinal chemistry. The interaction of [Pd(phen)(OAc)₂] (phen = 1,10-phenanthroline) with pivalic acid (^tBuCOOH) and trifluoromethanesulfonic acid (HOTf) leads to the formation of the molecular [...] Read more.

Obtaining water-soluble palladium complexes capable of interacting with DNA is an important synthetic task in medicinal chemistry. The interaction of [Pd(phen)(OAc)₂] (phen = 1,10-phenanthroline) with pivalic acid (^tBuCOOH) and trifluoromethanesulfonic acid (HOTf) leads to the formation of the molecular complex [Pd(phen)(OOC^tBu)₂] (1) and the ionic complex [Pd(phen)(H₂O)₂]Otf₂ (2), respectively. Complex 1 is highly soluble in water and stable in solution for 48 h. When complex 2 is boiled in water, it undergoes hydrolysis to form the binuclear hydroxo-bridged complex [Pd₂(phen)₂(μ-OH)₂]Otf₂ (3). According to X-ray diffraction data, the crystal lattices of 1–3 are stabilized by numerous intermolecular hydrogen bonds and π-π stacking interactions. The interaction of 1 and 2 with DNA in vitro (in 0.005 M NaCl solution) was studied using UV spectroscopy, low-gradient viscometry, and DNA melting analysis. It was shown that both compounds interact with DNA, and the binding is accompanied by the intercalation of the phenanthroline ligand at low concentrations in the DNA solution. An increase in their concentration leads to an alternative binding mode—palladium–DNA interaction causes a decrease in the DNA molecular coil size due to electrostatic interaction and/or palladium coordination to DNA bases. The difference between the binding of compounds 1 and 2 to DNA is that 2 can coordinate to N-bases, unlike complex 1. The antibacterial properties of the complexes have been studied in vitro against E. coli, P. aeruginosa, and S. aureus. Full article

(This article belongs to the Special Issue Metal Complexes as Potential Antimicrobial and Antiproliferative Agents)

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26 pages, 7422 KB

Open AccessArticle

Exothermic Effects and Viscosity of Oxide Melts Formed During High-Temperature Reduction of Cr–Mn Ore Systems

by Yerbolat Makhambetov, Sultan Kabylkanov, Saule Abdulina, Armat Zhakan, Azamat Burumbayev, Zhadiger Sadyk, Amankeldy Akhmetov, Zhalgas Saulebek, Ruslan Toleukadyr, Arnat Smagulov and Onuralp Yücel

Molecules 2026, 31(3), 575; https://doi.org/10.3390/molecules31030575 - 6 Feb 2026

Cited by 1 | Viewed by 401

Abstract

This study investigates the exothermic effects and viscosity properties of multicomponent oxide melts during the high-temperature reduction of low-grade Cr–Mn ores. Unlike previous thermodynamic-focused research, this work provides experimental evidence of transient exothermic responses and correlates them with melt properties. High-temperature experiments identified [...] Read more.

This study investigates the exothermic effects and viscosity properties of multicomponent oxide melts during the high-temperature reduction of low-grade Cr–Mn ores. Unlike previous thermodynamic-focused research, this work provides experimental evidence of transient exothermic responses and correlates them with melt properties. High-temperature experiments identified pronounced exothermic effects in the 800–1600 °C range. Phase analysis (XRD, SEM–EDS) confirmed effective Cr and Mn reduction into Fe–Cr–Mn–Si alloys with minimal residual oxides in the slag. Effective viscosity, measured via the electrovibrational method at 1400–1650 °C, decreased monotonically with temperature. Arrhenius analysis was applied to determine activation energies and crystallization onset temperatures (T_cr). The results indicate low viscosity and high thermal stability of the slags, ensuring efficient metal–slag separation. These findings confirm the technological feasibility of using low-grade ores for Fe–Cr–Mn alloy production and provide a basis for optimizing industrial smelting. Full article

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13 pages, 1832 KB

Open AccessArticle

Synthesis, Characterization, Molecular Docking, and Preliminary Biological Evaluation of 2-((4-Morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde

by Mokete Motente and Uche A. K. Chude-Okonkwo

Molecules 2026, 31(3), 574; https://doi.org/10.3390/molecules31030574 - 6 Feb 2026

Viewed by 475

Abstract

This study details the synthesis, characterization, molecular docking and preliminary biological evaluation of a new heterocyclic compound, 2-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde. This molecule was designed using an artificial intelligence (AI)-based molecular generative model. It was synthesized through a nucleophilic substitution between 3-chloro-4-morpholino-1,2,5-thiadiazole and 2-hydroxybenzaldehyde. Structural elucidation [...] Read more.

This study details the synthesis, characterization, molecular docking and preliminary biological evaluation of a new heterocyclic compound, 2-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde. This molecule was designed using an artificial intelligence (AI)-based molecular generative model. It was synthesized through a nucleophilic substitution between 3-chloro-4-morpholino-1,2,5-thiadiazole and 2-hydroxybenzaldehyde. Structural elucidation was performed using ¹H NMR, ¹³C NMR, Elemental Analysis, and Single Crystal X-ray diffraction. AI-guided in silico predictions suggested promising pharmacophoric features and potential biological activity. Preliminary biological evaluation, primarily through anticancer assays, demonstrated moderate to significant activity, supporting further investigation. The findings therefore suggest that this AI-generated molecule could serve as a lead scaffold for developing drugs targeting cancer and other infectious diseases. Full article

(This article belongs to the Section Medicinal Chemistry)

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22 pages, 4310 KB

Open AccessArticle

Novel Tyrosinase and α-Glucosidase Inhibitors: 1,3-Bisbenzylphenylphenol and Congeners as Cosmetic Whitening Agents Based on Natural Products

by Meng-Fei Wanyan, Xing Wu, Hui-Xiang Yang, Liang Tu, Qian Chen, Zhi-Hui Dong, Yu-Ting Tian, Xiao Lv, Qiong Chen, Hui-Hui Shen, Ting-Ting Deng, Zheng-Hui Li, Xian Wang, Rong Huang, Yong-Sheng Zheng and Ji-Kai Liu

Molecules 2026, 31(3), 573; https://doi.org/10.3390/molecules31030573 - 6 Feb 2026

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Abstract

New diarylheptene polyphenols with α-glucosidase inhibitory activity were previously isolated and reported from the aquatic plant Ottelia acuminata var. acuminata. It was used as the template in the present research, and a series of 1,3-bisbenzylphenylphenolic compounds were designed and synthesized. The tyrosinase, [...] Read more.

New diarylheptene polyphenols with α-glucosidase inhibitory activity were previously isolated and reported from the aquatic plant Ottelia acuminata var. acuminata. It was used as the template in the present research, and a series of 1,3-bisbenzylphenylphenolic compounds were designed and synthesized. The tyrosinase, α-glucosidase inhibitory effects, antioxidant properties, and whitening effects of these compounds were investigated. Of them, the representative compounds 1 and 2 inhibited the two target enzymes (tyrosinase and α-glucosidase) engaged in skin whitening and aging with comparable IC₅₀ values to the reference drugs as well as antioxidant activities. They showed potent whitening efficacy in zebrafish. In particular, compound 1 had whitening-effect rates of 31% at a concentration of 0.0001% (m/m), and 52% at a concentration of 0.0002% (m/m). Both compounds had more superior whitening efficacy than the commercially available whitening agent phenylethylresorcinol (377), which was used as a positive control. Compounds 1 and 2 did not show any genotoxicity and skin phototoxicity at the test concentrations, and they show promise as new skin-whitening agents. Full article

(This article belongs to the Section Bioorganic Chemistry)

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17 pages, 2809 KB

Open AccessArticle

Synthesis of Arapaima gigas Growth Hormone (ag-GH) in HEK 293 Cells: Its Purification and Characterization via In Vivo Bioassay in Dwarf “Little” Mice

by Eliana Rosa Lima, Jeniffer Cristina Ribeiro Melo, Filipe Menezes Bezerra, Miriam Fussae Suzuki, Amanda Palermo Nunes, Thais Cristina dos Anjos Sevilhano, João Ezequiel Oliveira, Riviane Garcez, Lucas Simon Torati, Geraldo Santana Magalhães, Cibele Nunes Peroni and Paolo Bartolini

Molecules 2026, 31(3), 572; https://doi.org/10.3390/molecules31030572 - 6 Feb 2026

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Abstract

Arapaima gigas growth hormone (ag-GH) cDNA was previously cloned from A. gigas pituitaries. In this work ag-GH has been synthesized using human embryonic kidney 293 cells (HEK293) transiently transfected with the 3.4-TOPO^® vector carrying ag-GH cDNA. The 4th day after transfection, the [...] Read more.

Arapaima gigas growth hormone (ag-GH) cDNA was previously cloned from A. gigas pituitaries. In this work ag-GH has been synthesized using human embryonic kidney 293 cells (HEK293) transiently transfected with the 3.4-TOPO^® vector carrying ag-GH cDNA. The 4th day after transfection, the presence of putative ag-GH was detected via SDS-PAGE and Western blotting in comparison with human GH. Ion exchange purification exhibited a clearly symmetric peak, absent in the control medium. The purified fraction, submitted to high-performance size-exclusion chromatography (HPSEC), SDS-PAGE, and Western blotting, contained an immunoreactive molecule, slightly smaller than hGH as expected. MALDI-TOF-MS determined a high-resolution molecular mass of 21,220 Da versus a theoretical value of 21,150. A phylogenetic analysis positioned ag-GH within basal teleost lineages, consistent with earlier analyses of A. gigas gonadotrophic hormones, reinforcing the structural and functional conservation relevant for its biologic activity. An in vivo bioassay based on the body weight increase of dwarf “little” mice demonstrated a biological activity for ag-GH comparable to that of the international reference preparation of rec-hGH. For two species (H. sapiens and A. gigas) separated by an evolutionary period of >100 million years, such a positive biological correlation is remarkable. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Chemical Biology)

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17 pages, 1245 KB

Open AccessReview

Auranofin Combination Therapy: A New Frontier in Cancer Treatment

by Diana Laura Guzman-Gomez, Srinivasa Reddy Telukutla, Ruchika Ojha, Suresh K. Bhargava and Magdalena Plebanski

Molecules 2026, 31(3), 571; https://doi.org/10.3390/molecules31030571 - 6 Feb 2026

Viewed by 739

Abstract

Auranofin, a gold(I)-based compound initially developed for the treatment of rheumatoid arthritis, has emerged as a promising anticancer agent with a multimodal mechanism of action. This review comprehensively examines the therapeutic potential of auranofin in oncology focusing on its ability to synergize with [...] Read more.

Auranofin, a gold(I)-based compound initially developed for the treatment of rheumatoid arthritis, has emerged as a promising anticancer agent with a multimodal mechanism of action. This review comprehensively examines the therapeutic potential of auranofin in oncology focusing on its ability to synergize with conventional and emerging cancer treatments. Here, we discuss the unique pharmacological properties of auranofin, including thioredoxin reductase inhibition, reactive oxygen species induction, and modulation of key apoptotic pathways. Moreover, this article highlights new recent evidence on its ability to synergize with other cancer treatments such as chemotherapy, immunotherapy, and targeted therapies. Particular emphasis is placed on the role of auranofin in overcoming drug resistance and its potential as an adjuvant in precision medicine. By analyzing both preclinical and clinical data, this review provides critical insights into the repositioning of auranofin as a versatile component in contemporary cancer treatment paradigms, while addressing current challenges and future directions for gold-based therapeutics in oncology. Full article

(This article belongs to the Special Issue Rational Design, Synthesis, and Evaluation of Small-Molecule Anticancer Agents)

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14 pages, 732 KB

Open AccessArticle

DECAF: Deconvoluted Extracted Ion Chromatogram-Based Quantification of Therapeutic Oligonucleotides

by Piotr Prostko, Youzhong Liu, Michał Aleksander Ciach, Tatsiana Khamiakova, Thomas De Vijlder and Dirk Valkenborg

Molecules 2026, 31(3), 570; https://doi.org/10.3390/molecules31030570 - 6 Feb 2026

Viewed by 604

Abstract

Accurate quantification in LC–MS experiments becomes challenging when analytes overlap both chromatographically and in mass spectra, as conventional extracted ion chromatogram-based methods can yield biased results by double-counting shared isotope signals. This limitation is particularly relevant for oligonucleotides, where degradation products and synthetic [...] Read more.

Accurate quantification in LC–MS experiments becomes challenging when analytes overlap both chromatographically and in mass spectra, as conventional extracted ion chromatogram-based methods can yield biased results by double-counting shared isotope signals. This limitation is particularly relevant for oligonucleotides, where degradation products and synthetic impurities frequently co-elute with the intended full-length product, complicating relative quantification. To address this, we developed DECAF, a straightforward and computationally efficient procedure for deconvoluting overlapping isotope patterns directly from MS1 data. The method models experimental isotope distributions as mixtures of theoretical templates across retention time, generating deconvoluted ion chromatograms whose peak areas accurately reflect the contributions of individual components. We demonstrate the utility of DECAF on two pharmaceutically relevant oligonucleotide mixture datasets, where it reliably estimated mixing proportions and enabled visualisation of component-specific elution profiles. Analysis of a typical sample required one to two minutes, underscoring the method’s practical efficiency. DECAF provides a transparent and accessible alternative to existing commercial software, with promising applications in pharmaceutical analysis and quality control. Full article

(This article belongs to the Special Issue Chromatography and Spectrometry in Food Safety and Pharmaceutical Analysis)

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13 pages, 691 KB

Open AccessArticle

Simultaneous UHPLC-UV Determination of Hericenones, Hericenes, Erinacines and Ergosterol in Hericium erinaceus Raw Materials or Products

by Yijin Tang, Ozan Kahraman, Anthony J. Goos and Christine Fields

Molecules 2026, 31(3), 569; https://doi.org/10.3390/molecules31030569 - 6 Feb 2026

Viewed by 813

Abstract

This study describes a single-laboratory validation of an ultra-high-performance liquid chromatographic (UHPLC) method for the determination of key compounds like hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus (H. erinaceus, Lion’s Mane) raw materials and finished products. The expanding market for [...] Read more.

This study describes a single-laboratory validation of an ultra-high-performance liquid chromatographic (UHPLC) method for the determination of key compounds like hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus (H. erinaceus, Lion’s Mane) raw materials and finished products. The expanding market for Hericium erinaceus (Lion’s Mane) has increased the need for practical, routine-ready analytical methods that can quantify characteristic marker compounds and strengthen quality control across both raw materials and finished products. In this study, an ultra-high-performance liquid chromatographic (UHPLC) separation method was developed for the determination of hericenones, hericenes, erinacines, and ergosterol in Hericium erinaceus raw materials and finished products. Under the optimized conditions, the major target analytes—hericenones, hericenes, erinacine A, and ergosterol—were fully resolved (R_s > 1.5) within 38 min using an HSS T3 column at 30 °C. All the peaks in the LC chromatogram of Hericium erinaceus samples and standard solutions were structurally confirmed by LC–UV-MS/MS based on the possible mass spectra. The quantitative calibration curves were linear, covering a range of 10–300 μg/mL for hericenone C, D and E, and hericene A, D and C; 3–100 μg/mL for deacylhericenone and deacylhericene; 1–50 μg/mL for erinacine A, and 5–200 μg/mL for ergosterol. Limits of quantification (LOQs) for hericenone C, D, and E and for hericene A, D, and C were approximately 9.263, 4.545, 4.650, 1.854, 10.72, and 11.18 µg/mL, respectively, while LOQs for deacylhericenone and deacylhericene were 1.083 and 2.109 µg/mL. Erinacine A and ergosterol showed LOQs of 0.642 and 8.352 µg/mL, respectively. The recovery of ergosterol was evaluated for the method at two different levels: 91.6~93.9% for 0.2% spiking and 93.0~102.6% for 0.08% spiking. The method was successfully validated, demonstrating inter-day Relative Standard Deviation (RSD) values between 1.1% and 5.7% for detected analytes across diverse matrices. This validated method provides a consistent quantification of hericenones, hericenes, erinacine A, and ergosterol across a range of commercial products and raw Hericium erinaceus materials, providing a sensitive and reliable tool for product characterization and quality control. This method provides QC laboratories with a robust, UV-based tool for standardized product characterization without requiring mass spectrometry. Full article

(This article belongs to the Collection Qualitative and Quantitative Analysis of Bioactive Natural Products)

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19 pages, 4552 KB

Open AccessArticle

Alkali-Modified Biochar Derived from Waste Bamboo Powder for the Effective Adsorption of Perfluorooctanoic Acid

by Long Lu, Hongbin Wang, Junfeng Zhao, Mei Zhang, Xuying Zheng, Dapeng Luo, Yongliang Sun and Jinyan Yang

Molecules 2026, 31(3), 568; https://doi.org/10.3390/molecules31030568 - 6 Feb 2026

Viewed by 448

Abstract

Bamboo powder waste generated from bamboo processing serves as an ideal feedstock for biochar (BC). This study employed potassium hydroxide (KOH) to modify biochar derived from bamboo powder waste, activating it at different temperatures (700 °C, 800 °C, and 900 °C) to yield [...] Read more.

Bamboo powder waste generated from bamboo processing serves as an ideal feedstock for biochar (BC). This study employed potassium hydroxide (KOH) to modify biochar derived from bamboo powder waste, activating it at different temperatures (700 °C, 800 °C, and 900 °C) to yield samples designated KBC-700, KBC-800, and KBC-900, respectively. The physicochemical properties and pore structures of the modified biochar were characterized using SEM, specific surface area and pore size analysis, FT-IR, Raman spectroscopy, XRD, and zeta potential measurements. The adsorption performance of the modified biochar toward PFOA was investigated using kinetic and thermodynamic models, examining the effects of the solution pH, adsorbent dosage, and temperature. Results indicate that KBC-900 exhibits a significantly enhanced specific surface area (up to 2924.7 m² g⁻¹), reduced surface oxygen-containing functional groups, increased carbon skeleton aromatization, and expanded mesoporous channels. Under initial conditions of pH = 3 and reaction temperature of 298 K, KBC-900 achieved a PFOA adsorption capacity of 366.7 mg g⁻¹ with a removal efficiency of 91.67%. The adsorption process conformed to pseudo-first-order and pseudo-second-order kinetic models as well as the Freundlich model. The adsorption equilibrium was reached within 12 h, indicating multi-layer adsorption dominated by chemisorption on a heterogeneous surface. Thermodynamic parameters indicate the adsorption reaction is an exothermic process. After five cycles of regeneration, KBC-900 maintained a removal efficiency of 75.69%. This study provides an efficient and reliable solution for removing PFOA from water. Full article

(This article belongs to the Special Issue Innovative Materials for Wastewater Treatment Applications)

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28 pages, 2279 KB

Open AccessReview

Beyond Resistance: Phenotypic Plasticity in Bacterial Responses to Antibiotics, Oxidative Stress and Antimicrobial Photodynamic Inactivation

by Aleksandra Rapacka-Zdonczyk

Molecules 2026, 31(3), 567; https://doi.org/10.3390/molecules31030567 - 6 Feb 2026

Cited by 1 | Viewed by 674

Abstract

The global challenge of antimicrobial resistance (AMR) has been framed primarily in terms of genetic resistance mechanisms. Nevertheless, bacteria can also survive antimicrobial stress through phenotypic plasticity, resulting in transient, non-genetic states such as tolerance, persistence, and population-level resilience. These phenotypic states complicate [...] Read more.

The global challenge of antimicrobial resistance (AMR) has been framed primarily in terms of genetic resistance mechanisms. Nevertheless, bacteria can also survive antimicrobial stress through phenotypic plasticity, resulting in transient, non-genetic states such as tolerance, persistence, and population-level resilience. These phenotypic states complicate diagnostic efforts, diminish antibiotic efficacy, and contribute to the chronic nature of infections even in the absence of heritable resistance. This review evaluates phenotypic plasticity as a significant yet underrecognized factor in AMR, with a focus on responses to oxidative and photodynamic stress. Key manifestations of plasticity are discussed, including morphological and metabolic remodeling such as filamentation, small-colony variants, and metabolic rewiring, as well as envelope- and biofilm-associated heterogeneity and regulatory flexibility mediated by gene networks and horizontal regulatory transfer. The review highlights plastic responses elicited by reactive oxygen species-mediated stress and antimicrobial photodynamic inactivation, where single-cell heterogeneity, biofilm and mucus barriers, and light-dependent cues influence bacterial survival. Case studies are presented to demonstrate how photodynamic strategies can induce transient protective states and act synergistically with antibiotics, revealing mechanisms of action that extend beyond conventional single-target therapeutic models. Drawing on evidence from single-cell analyses, biofilm ecology, and experimental evolution, this review establishes phenotypic plasticity as a central element in the chemical biology of AMR. Enhanced understanding of plasticity is essential for advancing diagnostics, informing the development of adjuvant therapies, and predicting bacterial responses to novel antimicrobial interventions. Full article

(This article belongs to the Special Issue Chemical Biology of Antimicrobial Resistance, 2nd Edition)

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13 pages, 2423 KB

Open AccessArticle

A DFT Study on Be_n(n = 10–12) Clusters with Hydrogen Storage Capacity

by Chunyu Yao, Shunping Shi, Zhanjiang Duan, Xiaoling Liu, Kai Diao, Jiabao Hu and Deliang Chen

Molecules 2026, 31(3), 566; https://doi.org/10.3390/molecules31030566 - 6 Feb 2026

Cited by 1 | Viewed by 529

Abstract

Hydrogen energy has garnered widespread attention as a clean energy source. This study employs density functional theory (DFT) to systematically investigate the hydrogen storage performance of Be_n(n = 10–12) clusters. The results reveal that hollow spherical Be_n clusters exhibit excellent [...] Read more.

Hydrogen energy has garnered widespread attention as a clean energy source. This study employs density functional theory (DFT) to systematically investigate the hydrogen storage performance of Be_n(n = 10–12) clusters. The results reveal that hollow spherical Be_n clusters exhibit excellent hydrogen storage capacity while maintaining good thermal stability even after H₂ adsorption at room temperature. Specifically, Be₁₀, Be₁₁ and Be₁₂ clusters can adsorb 26, 28, and 30 H₂ molecules, achieving hydrogen storage densities of 31.96 wt%, 31.87 wt%, and 35.87 wt%, respectively—far exceeding the U.S. Department of Energy’s target of 5.5 wt%. Calculations indicate an average adsorption energy between 0.16 and 0.19 eV/H₂, which lies between physisorption and chemisorption. IGMH isosurface analysis confirms the physisorption characteristics of H₂ molecules. PDOS analysis reveals that the hydrogen storage mechanism primarily originates from H₂ molecular polarization and van der Waals forces arising from orbital hybridization between hydrogen atoms and the substrate. Desorption temperature calculations show that, above 216 K, this material demonstrates potential for reversible hydrogen storage. This study demonstrates that these three hollow spherical beryllium cluster systems are ideal candidates for achieving ultra-high-capacity reversible hydrogen storage. Full article

(This article belongs to the Special Issue Advances in Density Functional Theory (DFT) Calculation)

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28 pages, 1351 KB

Open AccessReview

Small Particles, Big Impact: Inorganic Nanotechnology for Glioblastoma

by Klaudia Dynarowicz, David Aebisher, Jakub Tylutki, Nazarii Kozak, Aleksandra Kawczyk-Krupka and Dorota Bartusik-Aebisher

Molecules 2026, 31(3), 565; https://doi.org/10.3390/molecules31030565 - 6 Feb 2026

Viewed by 991

Abstract

Background: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors, with a median survival of only 15–17 months. Treatment failure is largely driven by the Blood–Brain Barrier (BBB), which restricts the delivery of most conventional therapeutics and shields invasive tumor [...] Read more.

Background: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors, with a median survival of only 15–17 months. Treatment failure is largely driven by the Blood–Brain Barrier (BBB), which restricts the delivery of most conventional therapeutics and shields invasive tumor regions from systemic drugs. Approach: This review highlights recent advances in inorganic nanoparticles designed to cross the BBB and target GBM. These platforms, including silica-, metal-, and carbon-based nanomaterials, enable multimodal applications such as tumor imaging, localized hyperthermia, and selective induction of cancer cell death. Functionalization with targeting ligands or surface modifications further enhances tumor penetration and therapeutic efficacy. Outlook: Despite promising preclinical results, clinical translation requires careful optimization of nanoparticle properties to minimize toxicity and immune clearance. Understanding these challenges provides a roadmap for the development of more effective nanomedicine strategies aimed at improving outcomes for GBM patients. Full article

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33 pages, 6390 KB

Open AccessArticle

Effect of n-Octadecylphosphonic Acid Coating on Zeolite 5A for Adsorptive Separation of Carbon Dioxide and Propylene

by Magdy Abdelghany Elsayed, Shixue Zhou, Chengdong Zhang and Kun Zhang

Molecules 2026, 31(3), 564; https://doi.org/10.3390/molecules31030564 - 5 Feb 2026

Viewed by 567

Abstract

Understanding the competitive adsorption mechanism is crucial for the rational design of CO₂ adsorbents. In this work, the surface of zeolite 5A was modified with varying concentrations of n-octadecylphosphonic acid (ODPA) to enhance the adsorptive separation of CO₂ over C [...] Read more.

Understanding the competitive adsorption mechanism is crucial for the rational design of CO₂ adsorbents. In this work, the surface of zeolite 5A was modified with varying concentrations of n-octadecylphosphonic acid (ODPA) to enhance the adsorptive separation of CO₂ over C₃H₆. With a 0.01 mol/L concentration of ODPA, the modified zeolite 5A achieves CO₂/C₃H₆ ideal selectivity over 73 at 298 K, a substantial improvement over the pristine zeolite 5A, which exhibits a selectivity of 6.07. The Sips isotherm model provides an excellent fit to the experimental data, offering insights into the adsorption mechanism, with a calculated enthalpy change of −30.70 kJ/mol for CO₂ and −16.54 kJ/mol for C₃H₆, along with favorable Gibbs free energy changes ranging from −9.00 to −3.54 kJ/mol for CO₂ and −4.96 to −2.04 kJ/mol for C₃H₆ over the temperature range of 298–373 K. Kinetic analysis reveals faster diffusion in pristine zeolite 5A; however, surface modification significantly enhances CO₂/C₃H₆ selectivity while maintaining balanced adsorption capacity. Adsorption uptakes of CO₂ and C₃H₆ in pristine zeolite 5A follow the pseudo-first-order model and pseudo-second-order model, respectively. Pristine zeolite 5A shows rapid adsorption, with a CO₂ adsorption capacity of 4.10 mmol/g with a rate constant of 2.60 min⁻¹, and a C₃H₆ adsorption capacity of 1.99 mmol/g with a rate constant of 0.34 min⁻¹. The modification with ODPA increases adsorption energy barriers, with CO₂ activation energy reaching 5.18 kJ/mol and C₃H₆ activation energy up to 15.63 kJ/mol, while tetrahydrofuran washing restores site accessibility, demonstrating tunable diffusion and adsorption behavior. These findings lay the foundation for designing high-efficiency, and selective adsorbents through targeted surface engineering. Full article

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19 pages, 966 KB

Open AccessArticle

Exploring Castanea sativa Shells (CSSs) as a Source of AKR1B1 and AKR1B10 Inhibitors: From Extraction to Bioactivity Testing

by Lucia Piazza, Lorena Tedeschi, Francesca Felice, Antonella Cecchettini, Elisa Ceccherini, Martina Avanatti, Adrian Florentin Suman, Francesco Balestri, Silvia Rocchiccioli and Giovanni Signore

Molecules 2026, 31(3), 563; https://doi.org/10.3390/molecules31030563 - 5 Feb 2026

Viewed by 485

Abstract

Chestnut shells are widely recognized as a source of bioactive compounds, including polyphenols and other antioxidant molecules. The industrial chestnut food chain generates large amounts of this by-product, which represents both a waste disposal challenge and a potential source of promising biomolecules. Thermal [...] Read more.

Chestnut shells are widely recognized as a source of bioactive compounds, including polyphenols and other antioxidant molecules. The industrial chestnut food chain generates large amounts of this by-product, which represents both a waste disposal challenge and a potential source of promising biomolecules. Thermal treatments occurring during industrial processing, however, may affect both chemical composition and bioactivity. Characterization of the chemical composition and biological activity of chestnut shells can contribute to the valorisation of this industrial by-product. Understanding which molecular alterations are caused by the processing is essential to assess the real potential of chestnut shell biomass. This study provides a comparative analysis of Castanea sativa shells, both raw and industrially processed. Evaluation was performed at different levels, exploiting mass spectrometry–based metabolite profiling, Total Phenolic Index analysis, antioxidant capacity, and inhibitory activity against AKR1B and AKR1B10, two reductases involved in key physiopathologic pathways. A comparison between extraction solvents (water and ethanol) and processing status (raw versus industrially processed) was performed. Overall, our results support the view that chestnut shell residues represent a valuable source of bioactive extracts. In a circular economy framework, such extracts could be developed to act on AKR1B1/AKR1B10 activity and oxidative stress, thereby contributing to the valorisation of chestnut processing by-products. Full article

(This article belongs to the Section Cross-Field Chemistry)

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18 pages, 1010 KB

Open AccessArticle

Linking Global Antioxidant Assays with Targeted HPLC Profiling of Prenylated Flavonoids in Humulus lupulus L. Extracts Obtained by Accelerated Solvent Extraction

by Nora Haring, Blažena Drábová and Milan Chňapek

Molecules 2026, 31(3), 562; https://doi.org/10.3390/molecules31030562 - 5 Feb 2026

Viewed by 298

Abstract

Accelerated solvent extraction (ASE) is widely used for recovering bioactive compounds from hops; however, the extent to which global antioxidant assays reflect changes in molecular composition remains unclear. This study evaluated the relationship between global antioxidant parameters and targeted profiling of prenylated flavonoids [...] Read more.

Accelerated solvent extraction (ASE) is widely used for recovering bioactive compounds from hops; however, the extent to which global antioxidant assays reflect changes in molecular composition remains unclear. This study evaluated the relationship between global antioxidant parameters and targeted profiling of prenylated flavonoids in hop extracts obtained under different ASE conditions. Total antioxidant capacity (TAC), total phenolic content (TPC), and concentrations of xanthohumol, isoxanthohumol, and 8-prenylnaringenin were determined in extracts prepared using different solvents, extraction temperatures, and homogenization approaches. Global antioxidant parameters responded consistently to technological factors and exhibited a strong mutual correlation. In contrast, their correlations with individual prenylated flavonoids were moderate, indicating that global assays capture only part of the variability associated with specific bioactive compounds. Extraction temperature emerged as a key modulating factor, inducing compound-specific and partly non-linear responses that were not fully reflected by global antioxidant methods. Principal component analysis confirmed a shared chemical trend linking global and targeted parameters while separating extraction temperature as an independent technological driver. Overall, global antioxidant assays provide a robust but simplified assessment of hop extract quality. Their combination with targeted chromatographic analysis enables more accurate interpretation of extraction behavior and supports informed process optimization aimed at preserving and recovering bioactive compounds. Full article

(This article belongs to the Section Analytical Chemistry)

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25 pages, 3065 KB

Open AccessArticle

From Elderflower to Bioactive Extracts: Phytochemical Characterization and Anti-Inflammatory Activity

by Maryna Koval, Sławomir Dresler, Sandra Kowalik, Benedikt Schwarz, Anna Wawruszak, Anna Filipek, Małgorzata Komar, Thomas Jakschitz, Stavros Beteinakis, Günther Bonn, Wojciech Koch and Wirginia Kukula-Koch

Molecules 2026, 31(3), 561; https://doi.org/10.3390/molecules31030561 - 5 Feb 2026

Viewed by 735

Abstract

This study provides a phytochemical characterization of Sambucus nigra L. (elderflower) and correlates its chemical profile with anti-inflammatory bioactivity, establishing an optimized extraction methodology. A comparative analysis of ultrasound-assisted extraction (UAE), accelerated solvent extraction (ASE), and shaking maceration was conducted using solvents of [...] Read more.

This study provides a phytochemical characterization of Sambucus nigra L. (elderflower) and correlates its chemical profile with anti-inflammatory bioactivity, establishing an optimized extraction methodology. A comparative analysis of ultrasound-assisted extraction (UAE), accelerated solvent extraction (ASE), and shaking maceration was conducted using solvents of varying polarity (ethanol, ethanol–water mixture (1:1, v/v), and water). High-resolution fingerprinting via HPLC-ESI-QTOF-MS/MS confirmed a rich polyphenolic profile, dominated by flavonoids such as rutin, naringenin, and phenolic acids, notably chlorogenic acid. Quantitative analysis revealed that UAE with ethanol–water mixture (1:1, v/v) for 20 min yielded the highest recovery of rutin (4.87%) and chlorogenic acid (8.22%). The anti-inflammatory potential was evaluated in TNFα-stimulated HaCaT NF-κB Luc reporter keratinocytes. Anhydrous ethanolic extracts demonstrated superior efficacy, significantly inhibiting NF-κB pathway activation at non-cytotoxic concentrations. Chemometric analysis, specifically PLS-DA, identified naringenin as a principal contributor to this observed anti-inflammatory effect. These findings underscore the critical role of solvent selection in modulating the phytochemical composition and resultant bioefficacy of elderflower extracts. The potent, naringenin-driven inhibition of NF-κB in keratinocytes highlights the significant therapeutic potential of optimized S. nigra extracts for applications in dermatological and cosmetic formulations aimed at managing inflammatory skin disorders. Full article

(This article belongs to the Special Issue Anti-Aging and Skin Rejuvenation Ingredients: Design and Research)

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22 pages, 4000 KB

Open AccessReview

Enhancing Tumor Photodynamic Therapy via Molecular Engineering and Functional Modification of Photosensitizers

by Wei Zheng, Linlin Tao, Xiaofeng Xia, Tianlin Wang and Feiyi Wang

Molecules 2026, 31(3), 560; https://doi.org/10.3390/molecules31030560 - 5 Feb 2026

Cited by 1 | Viewed by 704

Abstract

Photosensitizers are susceptible to interference from the biological internal environment, which largely restricts the clinical application of photodynamic therapy. For instance, most existing photosensitizers tend to aggregate in the biological environment, resulting in a decrease in reactive oxygen species yield; their therapeutic efficacy [...] Read more.

Photosensitizers are susceptible to interference from the biological internal environment, which largely restricts the clinical application of photodynamic therapy. For instance, most existing photosensitizers tend to aggregate in the biological environment, resulting in a decrease in reactive oxygen species yield; their therapeutic efficacy is unsatisfactory in hypoxic tumor environments; they are difficult to accumulate effectively in tumor sites and cannot accurately distinguish between tumors and healthy tissues. To address these issues, this review systematically elaborates on a series of optimization strategies, including improving the intersystem crossing efficiency of photosensitizers through molecular engineering, endowing them with aggregation-induced emission properties, developing type I photosensitizers, and functionalizing photosensitizers by modifying biological proteins, targeting groups, or combining with nanoengineering, aiming to enhance the efficiency of photodynamic therapy. By summarizing the latest research breakthroughs, innovative methods, and emerging applications in this field, the review provides practical solutions and broad application prospects for photodynamic therapy, which is expected to promote the clinical translation and application of photosensitizers. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Bioorganic Chemistry)

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23 pages, 1333 KB

Open AccessReview

Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation

by Junyi Duan, Daoyuan Huang and Yick W. Fong

Molecules 2026, 31(3), 559; https://doi.org/10.3390/molecules31030559 - 5 Feb 2026

Viewed by 749

Abstract

The unfolded protein response (UPR) is a highly conserved adaptive mechanism that restores endoplasmic reticulum (ER) homeostasis under stress. Beyond its canonical roles in proteostasis, the UPR has emerged as a central regulator of immune responses across diverse contexts, including infection, inflammation, cancer, [...] Read more.

The unfolded protein response (UPR) is a highly conserved adaptive mechanism that restores endoplasmic reticulum (ER) homeostasis under stress. Beyond its canonical roles in proteostasis, the UPR has emerged as a central regulator of immune responses across diverse contexts, including infection, inflammation, cancer, and autoimmunity. IRE1α, PERK, and ATF6 are three principal UPR sensors that coordinate complex signaling networks to regulate antigen presentation, cytokine production, and immune cell differentiation. This review highlights the molecular mechanisms by which small molecules target the UPR to modulate immune responses. In addition, we highlight stress granules (SGs) and the prevalence of protein–protein interactions mediated by intrinsically low-complexity domains (LCDs) in the UPR as potential new avenues for immune modulation. Finally, we discuss future directions for leveraging UPR modulation in immunotherapy, infectious disease, and chronic inflammatory disorders. Full article

(This article belongs to the Special Issue Small-Molecule Targeted Drugs)

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12 pages, 1558 KB

Open AccessArticle

Secondary Metabolites with Antithrombotic and Antioxidant Activities Derived from Cordyceps cicadae

by Xingze Hu, Guisheng Wang, Tao Chen, Xinyue Zhang, Jianying Wu, Guang Shao, Runlin Cai and Zhigang She

Molecules 2026, 31(3), 558; https://doi.org/10.3390/molecules31030558 - 5 Feb 2026

Viewed by 394

Abstract

Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, [...] Read more.

Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, one unreported flavonoid; quercetin-3-O-β-D-methylglucopyranoside (1); three known flavonoids (2–4); and one new dicarboxylic acid derivative, cicadae acid (5), were isolated from C. cicadae. Their chemical structures were elucidated by a comprehensive spectroscopic analysis (1D/2D NMR and HRESIMS), electronic circular dichroism (ECD) calculations, a DP4+ probability analysis, and the modified Mosher method. All compounds exhibited significant antithrombotic effects at a concentration of 20 μM in a zebrafish model. Compounds 1–4 exhibited potent antioxidant activity in the DPPH radical scavenging assay, with IC₅₀ values ranging from 12.81 ± 3.42 to 20.16 ± 2.64 μM. These findings provide scientific evidence supporting the traditional application of C. cicadae, identifying specific flavonoids and dicarboxylic acids as potential therapeutic agents for thrombosis and oxidative stress-related disorders. Full article

(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)

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15 pages, 119310 KB

Open AccessArticle

Ginsenoside Rg5 Targets PRDX1 to Disrupt Redox Homeostasis and Induce Mitochondria-Dependent Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

by Hai-Lun Ye, Ya-Ni Wang, Gang-Ao Li, Xing-Hui Jin, Guan-Ting Wu, Yang Li and Ying-Hua Jin

Molecules 2026, 31(3), 557; https://doi.org/10.3390/molecules31030557 - 5 Feb 2026

Viewed by 530

Abstract

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options and poor clinical outcomes. Mounting evidence suggests that targeting cancer-specific metabolic and redox adaptations represents a promising therapeutic strategy. Peroxiredoxin 1 (PRDX1), a key antioxidant enzyme [...] Read more.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with limited therapeutic options and poor clinical outcomes. Mounting evidence suggests that targeting cancer-specific metabolic and redox adaptations represents a promising therapeutic strategy. Peroxiredoxin 1 (PRDX1), a key antioxidant enzyme that is frequently overexpressed in HCC, enables tumor cells to neutralize excessive reactive oxygen species (ROS), thereby sustaining survival and conferring therapeutic resistance. In this study, using human hepatocellular carcinoma HepG2 cells as an in vitro model, we identify ginsenoside Rg5 (Rg5) as a previously unrecognized small-molecule inhibitor of PRDX1. Structural and functional analyses demonstrate that Rg5 directly binds to the Asn145 residue of PRDX1, effectively suppressing its peroxidase activity. Mechanistically, this inhibition disrupts ROS detoxification in HepG2 cells, leading to mitochondrial ROS accumulation, activation of the intrinsic apoptotic pathway, and consequent HepG2 cell death. Additionally, Rg5 not only suppresses HepG2 cell survival but also acts synergistically with doxorubicin, a first-line chemotherapeutic agent, to markedly enhance antitumor efficacy and potentially mitigate chemoresistance. Collectively, these findings suggest that PRDX1 inhibition may represent a broadly exploitable vulnerability in liver cancer and establish Rg5 as a promising candidate for developing targeted and combinatorial therapies against HCC. Full article

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19 pages, 4551 KB

Open AccessReview

Fatty Acid Amide Hydrolase Signaling and Ovarian Disorders: From Molecular Mechanism to Clinical Significance

by Qinghe Lin, Zhenghong Zhang, Defan Wang, Fan Wang and Zhengchao Wang

Molecules 2026, 31(3), 556; https://doi.org/10.3390/molecules31030556 - 5 Feb 2026

Viewed by 1646

Abstract

Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology [...] Read more.

Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology is receiving increasing attention. Accumulating evidence indicates that FAAH participates in several important ovarian processes, including follicular development, steroid hormone synthesis, ovulation, and luteal function. In this review, we outline the biochemical properties of FAAH and its spatial distribution in ovarian tissues, with a particular focus on how FAAH-mediated AEA metabolism contributes to intraovarian signaling. Furthermore, we highlight the potential implications of altered FAAH activity in ovarian disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and infertility. By integrating molecular observations with clinical findings, this work provides updated perspectives on FAAH as both a physiological regulator and a potential therapeutic target in reproductive medicine. Full article

(This article belongs to the Special Issue Signaling Pathways as Targets in Disease Therapy)

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21 pages, 5158 KB

Open AccessArticle

Natural Isothiocyanates Block Adhesion and Invasion of Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines

by Jochen Rutz, Timothy Grein, Marina Laqua, Kenza Benhassine, Eren Perktas, Jindrich Cinatl, Anita Thomas, Felix K.-H. Chun, Axel Haferkamp, Eva Juengel, Igor Tsaur, Sascha D. Markowitsch and Roman A. Blaheta

Molecules 2026, 31(3), 555; https://doi.org/10.3390/molecules31030555 - 5 Feb 2026

Viewed by 728

Abstract

Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP [...] Read more.

Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP bladder cancer cell lines was investigated. Parameters determined were: cell interaction with collagen or fibronectin, chemotaxis, and membrane receptors involved in adhesion (total and activated integrins β1, β4, β5, CD44s, and CD44v3-v7). CD44s’ location and adhesion- and migration-related signaling proteins were determined. AITC blocked adhesion of almost all sensitive and resistant cancer cells. PEITC and BITC suppressed fibronectin interaction of sensitive and resistant RT112. All three isothiocyanates diminished chemotaxis in all cell lines. Integrin expression was differentially altered but CD44s and CD44v were not altered. BITC and PEITC translocated CD44s from the cell membrane to cytoplasm. The tumor suppressor E-cadherin increased, whereas focal adhesion kinase (FAK), linked to integrin signaling, was deactivated after isothiocyanate treatment. Blocking FAK, β1, β4, or β5 was associated with reduced chemotaxis. Thus, AITC, BITC, and PEITC blocked adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells. This was associated with altered integrin expression and signaling, CD44s translocation, and enhanced E-cadherin. Full article

(This article belongs to the Section Natural Products Chemistry)

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22 pages, 5147 KB

Open AccessArticle

A UHPLC-Orbitrap-MS Metabolomics Strategy Reveals Glycerophospholipid Metabolic Remodeling Is Associated with the Anti-Arthritic Effect of Glycyrrhiza Protein–Paeoniflorin Nanoparticles via PI3K/AKT/NLRP3 Axis

by Na Zhang, Xiaoyun Yang, Cui Li, Miaoxin Huo, Yuan Gao, Dong Bai and Yuqin Yang

Molecules 2026, 31(3), 554; https://doi.org/10.3390/molecules31030554 - 5 Feb 2026

Viewed by 480

Abstract

Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein–paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 [...] Read more.

Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein–paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 mice (n = 42) were assigned to the control, model, GP-PF NPs, paeoniflorin, glycyrrhiza protein, physical mixture, and celecoxib groups. All groups except controls received complete Freund’s adjuvant, and treatments were given intraperitoneally for 10 days. GP-PF NPs produced the greatest reduction in paw thickness versus the model (p < 0.0001) and outperformed all other active treatments, which was consistent with the improved histopathology. UHPLC-Orbitrap-MS detected 473 serum metabolites, and the model group showed 59 significant changes versus the control. GP-PF NPs significantly modulated 108 metabolites and yielded robust OPLS-DA separation from the model (R²Y = 0.98; Q² = 0.742). Venn and pathway analyses identified 43 NP-specific metabolites enriched in glycerophospholipid metabolism, including glycerophosphocholine, 1-oleylglycerophosphocholine, PE (16:0/16:0), phosphocholine, and sphingosine-1-phosphate. These metabolites were selectively normalized toward control levels by GP-PF NPs. qPCR further showed that GP-PF NPs significantly reduced synovial PI3K, AKT, mTOR, NLRP3, Caspase-1, and GSDMD mRNA overexpression (all p < 0.001 vs. model). Correlation analysis indicated significant associations between key serum lipids and synovial genes (e.g., PI3K positively correlated with several metabolites, r = 0.71–0.82; mTOR negatively correlated with sphinganine 1-phosphate and glycerophosphocholine, r = −0.65 and −0.54). These data suggest that GP-PF NPs ameliorate AIA and are associated with the normalization of glycerophospholipid-related metabolic perturbations and reduced synovial mRNA expression of the PI3K/AKT/mTOR-NLRP3 pathway, supporting their potential as a metabolism-inflammation preclinical oriented anti-arthritic nanomedicine. Full article

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20 pages, 1583 KB

Open AccessArticle

Pick-Up of Organic Molecules by Mixed Ar Clusters: A Function of Gas Properties and Composition

by Jernej Ekar and Oksana Plekan

Molecules 2026, 31(3), 553; https://doi.org/10.3390/molecules31030553 - 5 Feb 2026

Viewed by 521

Abstract

Clusters present an intriguing field of research, with their properties bridging the gap between an isolated atom/molecule and a bulk. They can act as a substrate for dopant molecules picked up on the fly and located on or inside the cluster. Our research [...] Read more.

Clusters present an intriguing field of research, with their properties bridging the gap between an isolated atom/molecule and a bulk. They can act as a substrate for dopant molecules picked up on the fly and located on or inside the cluster. Our research on Ar clusters reveals that gas pressure and composition are crucial parameters determining the pickup probability for molecules such as adenine, uracil, glycine, and ascorbic acid. For pure Ar expansion, the most intense molecular signals are observed in the stagnation pressure range between 10 and 30 bar. Adding up to 33 mol% of He or O₂ at fixed total pressure causes no change in the intensity of dopant and Ar oligomer signals. The addition of N₂O or CO₂ results in a significant intensity drop, with signals from the molecule and Ar oligomers disappearing above 3 mol% of N₂O or CO₂. The opposite effects are observed with the Ar-H₂ mixture at a pressure of 25 bar. Optimal results are obtained for H₂ concentrations between 40 and 50 mol% versus D₂ concentrations between 20 and 35 mol%. Substitution of Ar with an Ar-H₂ mixture causes signal intensities of dopants and Ar oligomers to increase by more than threefold. Full article

(This article belongs to the Special Issue The 30th Anniversary of Molecules—Recent Advances in Nanochemistry)

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14 pages, 2525 KB

Open AccessArticle

Releasing the Constraints on the Catalytic Performance of Ballast Stone in Co-N-C Materials

by Mingzhu Gao, Xiaogeng Zhao, Xingmian Zhang, Yunhui Hao, Junna Feng, Hong Su, Changbin Zhu, Shengman Wang, Xue Li, Chun Wang, Junmin Wang and Cheng Feng

Molecules 2026, 31(3), 552; https://doi.org/10.3390/molecules31030552 - 5 Feb 2026

Viewed by 423

Abstract

For Co-N-C materials prepared under high-temperature calcination conditions, the formation of Co nanoparticles occurs when the metal loading exceeds 2%. Typically, CoNx is regarded as the primary active site of the catalyst, while Co nanoparticles are considered to possess limited catalytic activity. Consequently, [...] Read more.

For Co-N-C materials prepared under high-temperature calcination conditions, the formation of Co nanoparticles occurs when the metal loading exceeds 2%. Typically, CoNx is regarded as the primary active site of the catalyst, while Co nanoparticles are considered to possess limited catalytic activity. Consequently, within Co-N-C materials, Co nanoparticles are often likened to ‘ballast stone’ in a catalyst. In the model reaction of formic acid dehydrogenation, we incorporated boron into the precursor, thereby enhancing the electronic metal-support interactions (EMSI) between Co nanoparticles and carbon carriers. Consequently, this modification resulted in a catalytic performance of Co nanoparticles that was comparable to that of Co single-atom catalysts (SACs). Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Applied Chemistry)

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33 pages, 1962 KB

Open AccessReview

Iodinated Contrast Media—From Clinical Use to Environmental Concern and Treatment Possibilities

by Katarzyna Wrzesińska, Michał Kwiatkowski, Piotr Terebun, Dawid Zarzeczny, Agata Sumara, Tomoyuki Murakami, Nobuya Hayashi, Frantisek Krcma, Evgenia Benova, Karol Hensel, Zdenko Machala, Emilia Fornal and Joanna Pawłat

Molecules 2026, 31(3), 551; https://doi.org/10.3390/molecules31030551 - 4 Feb 2026

Viewed by 1220

Abstract

Iodine-based contrast agents (ICMs) are crucial substances in medical imaging because of their potent X-ray characteristics and chemical stability. However, their persistence and poor removal in conventional wastewater treatment have led to increasing environmental concern. Although ICMs exhibit low acute toxicity, their transformation [...] Read more.

Iodine-based contrast agents (ICMs) are crucial substances in medical imaging because of their potent X-ray characteristics and chemical stability. However, their persistence and poor removal in conventional wastewater treatment have led to increasing environmental concern. Although ICMs exhibit low acute toxicity, their transformation during water disinfection can generate iodine-based disinfection by-products (I-DBPs), like iodo-trihalomethanes, which display notable cytotoxic, genotoxic, and ecotoxic effects and compromise drinking water quality. Advanced oxidation processes (AOPs) have become promising methods for breaking down persistent ICMs and limiting the formation of I-DBPs. Techniques including ozonation, UV/H₂O₂, UV/chlorine, photocatalysis with TiO₂, Fenton reactions, and electrochemical oxidation utilize highly reactive radicals to decompose persistent compounds like iopamidol, iohexol, iopromide, and diatrizoate. Despite high degradation efficiencies under laboratory conditions, limitations such as incomplete mineralization, secondary product formation, and elevated operational costs hinder large-scale implementation. Future research should focus on optimizing AOP conditions under realistic water matrices, evaluating by-product toxicity, and developing cost-effective hybrid systems. Advancing these technologies is critical to reducing the environmental burden of ICMs and safeguarding aquatic ecosystems and public health. Full article

(This article belongs to the Special Issue Review Papers in Physical Chemistry)

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16 pages, 1796 KB

Open AccessArticle

Comprehensive Profiling of Triglycerides in Wild Eastern Mediterranean Echium Seed Oil Using Paternò–Büchi Modulated Lipidomics

by Manal Alhusban, Suha Telfah, Mohammad M. Al-Gharaibeh, Sanaa Bardaweel, Raghad Alkadri and Fang Wei

Molecules 2026, 31(3), 550; https://doi.org/10.3390/molecules31030550 - 4 Feb 2026

Viewed by 545

Abstract

Currently, ω-3 polyunsaturated fatty acids (PUFAs), which have become popular as dietary supplements, are limited by a shortage in supply. Thus, finding safe, effective alternatives is crucial. Echium seed oil (ESO), rich in α-linolenic acid (ALA, 18:3ω-3) and stearidonic acid (SDA, 18:4ω-3), surpasses [...] Read more.

Currently, ω-3 polyunsaturated fatty acids (PUFAs), which have become popular as dietary supplements, are limited by a shortage in supply. Thus, finding safe, effective alternatives is crucial. Echium seed oil (ESO), rich in α-linolenic acid (ALA, 18:3ω-3) and stearidonic acid (SDA, 18:4ω-3), surpasses many other botanical seed oils. In this study, a pseudotargeted approach was applied to characterize the lipidomic profile of two unexplored Echium species from the Mediterranean region. Our findings established Echium glomeratum as a rich source of ω-3 fatty acids (FAs), exceeding many other species in both quality and quantity. E. glomeratum possesses different FAs and triglyceride (TG) profiles compared to E. judaeum, with the ω-3:ω-6 ratio being 3.5 and 1.3, respectively. This corresponds to higher quantities of ALA (45.50%) and SDA (12.59%) in E. glomeratum. Triglycerides (TGs) comprise 93% of the total lipid content in ESO. This study also profiled the most abundant TGs (50–60 carbons) from both species through comprehensive assignment of the olefination patterns. The E. glomeratum oil profile, containing a higher ω-3 PUFA concentration, was further screened for cytotoxic and antioxidant activities. Our preliminary results demonstrated that E. glomeratum ESO may significantly suppress colon cancer cell growth. Full article

(This article belongs to the Special Issue New Achievements and Challenges in Food Chemistry, 2nd Edition)

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28 pages, 27267 KB

Open AccessArticle

Selective Cytotoxic and Antiproliferative Effects of Extracts from Four Mexican Medicinal Plants in Human Cancer and Non-Cancerous Cell Lines

by Joel Daniel Castañeda-Espinoza, Yessica Arisbeth Alvarez Soto, Silvia Marquina-Bahena, Guillermo Antonio Madariaga Sosa, Karina Lizbeth Zagal Laguna, Araceli Guerrero-Alonso, Enrique Salas-Vidal, Janette Furuzawa-Carballeda, Juan M. Uriostegui-Velarde, Carlos Mojica Cardoso, Abraham Noé Anzurez Jiménez, Estela Carranza Valencia, Erick Ayala Calvillo and Jessica Nayelli Sánchez-Carranza

Molecules 2026, 31(3), 549; https://doi.org/10.3390/molecules31030549 - 4 Feb 2026

Viewed by 750

Abstract

Background: Medicinal plants used in traditional Mexican medicine represent a valuable source of bioactive compounds with potential anticancer activity. Beyond cytotoxic potency, selectivity toward cancer cells over normal cells is a critical toxicological parameter for identifying safer therapeutic candidates. This study aimed [...] Read more.

Background: Medicinal plants used in traditional Mexican medicine represent a valuable source of bioactive compounds with potential anticancer activity. Beyond cytotoxic potency, selectivity toward cancer cells over normal cells is a critical toxicological parameter for identifying safer therapeutic candidates. This study aimed to evaluate the selective cytotoxic and antiproliferative effects of extracts from four Mexican medicinal plants across human cancerous and non-cancerous cell lines. Methods: Hexane, acetone, and methanolic extracts from Semialarium mexicanum, Eryngium heterophyllum, Piper auritum, and Cochlospermum vitifolium were evaluated in a panel of human cancer cell lines and non-tumoral models, including primary human uterine fibroblasts (HUFs). Cytotoxicity was assessed after 48 h of treatment using increasing extract concentrations, and selectivity indices were calculated. Cell cycle distribution and nuclear morphology analyses were performed to explore antiproliferative effects. Additionally, GC–MS-based chemical profiling was conducted on selected extracts to obtain a tentative characterization of major bioactive constituents. Results: The extracts exhibited differential cytotoxic profiles depending on plant species and solvent polarity. The hexane extract of Semialarium mexicanum showed the highest cytotoxic potency and selectivity toward cervical cancer cells, with half-maximal inhibitory concentration (IC₅₀); values of 15.9 ± 1.8 µg/mL and 17.2 ± 2.8 µg/mL in HeLa and SiHa cells, respectively, and selectivity index (SI) values > 5 when compared with primary human uterine fibroblasts (HUF). Extracts of Eryngium heterophyllum displayed moderate cytotoxic activity (IC₅₀ = 20–30 µg/mL in HeLa cells) with intermediate selectivity, whereas Cochlospermum vitifolium showed solvent-dependent effects and Piper auritum exhibited limited cytotoxicity. Cell cycle analysis revealed an increased sub-G1 population, and nuclear morphology assays demonstrated chromatin condensation and fragmentation in cancer cells, supporting an antiproliferative mechanism. GC–MS analysis of the hexane extract of Semialarium mexicanum suggested the presence of triterpenoid-related and other lipophilic compounds potentially associated with its selective anticancer activity. Conclusions: These findings provide in vitro evidence of selective anticancer activity of Mexican medicinal plant extracts and establish a basis for future mechanistic studies medicinal plant extracts and lay the groundwork for future mechanistic investigations. Full article

(This article belongs to the Special Issue Recent Advances in the Toxicology and Safety of Medicinal Plants and Natural Products)

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Molecules, Volume 31, Issue 3 (February-1 2026) – 186 articles

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