Molecules

19 pages, 753 KiB

Open AccessReview

Neuroprotective Role of Omega-3 Fatty Acids: Fighting Alzheimer’s Disease

by Mervin Chávez-Castillo, María Paula Gotera, Pablo Duran, María P. Díaz, Manuel Nava, Clímaco Cano, Edgar Díaz-Camargo, Gabriel Cano, Raquel Cano, Diego Rivera-Porras and Valmore Bermúdez

Molecules 2025, 30(15), 3057; https://doi.org/10.3390/molecules30153057 (registering DOI) - 22 Jul 2025

Abstract

Alzheimer’s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order to solve this problem, new strategies have been investigated over recent years for AD treatment. This field has been reborn due to epidemiological and preclinical findings that demonstrate the fact that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can be promising therapeutic agents because of their anti-inflammatory, antioxidant, and neurogenic-promoting activities, thus allowing us to classify these molecules as neuroprotectors. Similarly, ω-3 PUFAs perform important actions in the formation of characteristic AD lesions, amyloid-β plaques (Aβ) and neurofibrillary tangles, reducing the development of these structures. Altogether, the aforementioned actions hinder cognitive decline and possibly reduce AD development. In addition, ω-3 PUFAs modulate the inflammatory response by inhibiting the production of pro-inflammatory molecules and promoting the synthesis of specialised pro-resolving mediators. Consequently, the present review assesses the mechanisms by which ω-3 PUFAs can act as therapeutic molecules and the effectiveness of their use in patients. Clinical evidence so far has shown promising results on ω-3 PUFA effects, both in animal and epidemiological studies, but remains contradictory in clinical trials. More research on these molecules and their neuroprotective effects in AD is needed, as well as the establishment of future guidelines to obtain more reproducible results on this matter. Full article

(This article belongs to the Special Issue Bioactive Compounds and Small Molecules with Neuroprotective and Anti-Inflammatory Functions)

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22 pages, 1008 KiB

Open AccessReview

Ap4A in Cancer: A Multifaceted Regulator and Emerging Therapeutic Target

by Kateryna Tkachenko, Tiziana Bachetti and Camillo Rosano

Molecules 2025, 30(15), 3056; https://doi.org/10.3390/molecules30153056 (registering DOI) - 22 Jul 2025

Abstract

Diadenosine polyphosphates, including diadenosine tetraphosphate (Ap4A), are ubiquitous nucleotides that are present across diverse life forms, gaining considerable interest due to their role as cellular signaling molecules. Ap4A, in particular, has been extensively researched in various biological systems, especially under conditions of environmental stress. This review provides an in-depth analysis of the current knowledge surrounding Ap4A, focusing on its biosynthesis and degradation pathways, the identification of Ap4A protein targets and the molecular mechanisms underlying its action. Furthermore, this review aims to examine the interplay between the various pathogenetic mechanisms driving tumor development and the potential role of Ap4A which emerges as pivotal signaling molecules orchestrating cellular responses to environmental challenges, positioning them at the nexus of cancer adaptation and progression. Full article

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26 pages, 24382 KiB

Open AccessArticle

Carboxylated Mesoporous Carbon Nanoparticles as Bicalutamide Carriers with Improved Biopharmaceutical and Chemo-Photothermal Characteristics

by Teodora Popova, Borislav Tzankov, Marta Slavkova, Yordan Yordanov, Denitsa Stefanova, Virginia Tzankova, Diana Tzankova, Ivanka Spassova, Daniela Kovacheva and Christina Voycheva

Molecules 2025, 30(15), 3055; https://doi.org/10.3390/molecules30153055 (registering DOI) - 22 Jul 2025

Abstract

Prostate cancer is a serious, life-threatening condition among men, usually requiring long-term chemotherapy. Due to its high efficacy, bicalutamide, a non-steroidal anti-androgen, has widespread use. However, its poor water solubility, low oral bioavailability, and nonspecific systemic exposure limit its application. To overcome these obstacles, our study explored the potential of non-carboxylated and carboxylated mesoporous carbon nanoparticles (MCN) as advanced drug carriers for bicalutamide (MCN/B and MCN-COOH/B). The physicochemical properties and release behaviour were thoroughly characterized. Functionalization with carboxylic groups significantly improved wettability, dispersion stability, as well as loading efficiency due to enhanced hydrogen bonding and π–π stacking interactions. Moreover, all systems exhibited sustained and near-infrared (NIR) triggered drug release with reduced burst-effect, compared to the release of free bicalutamide. Higher particle size and stronger drug–carrier interactions determined a zero-order kinetics and notably slower release rate of MCN-COOH/B compared to non-functionalized MCN. Cytotoxicity assays on LNCaP prostate cancer cells demonstrated that both MCN/B and MCN-COOH/B possessed comparable antiproliferative activity as free bicalutamide, where MCN-COOH/B exhibited superior efficacy, especially under NIR exposure. These findings suggest that MCN-COOH nanoparticles could be considered as a prospective platform for controlled, NIR-accelerated delivery of bicalutamide in prostate cancer treatment. Full article

(This article belongs to the Special Issue Mesoporous Silica and Related Nanomaterials: Synthesis, Characterization and Applications in Drug Delivery Systems and Green Chemistry)

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16 pages, 2682 KiB

Open AccessArticle

Modulatory Effect of Curcumin on Expression of Methyltransferase/Demethylase in Colon Cancer Cells: Impact on wt p53, mutp53 and c-Myc

by Roberta Santarelli, Claudia Di Dio, Michele Di Crosta, Paola Currà, Roberta Gonnella and Mara Cirone

Molecules 2025, 30(15), 3054; https://doi.org/10.3390/molecules30153054 (registering DOI) - 22 Jul 2025

Abstract

Curcumin-mediated anti-cancer properties have been correlated with the inhibition of oncogenic molecules such as mutp53 and c-Myc. Their targeting is therapeutically significant, as p53, following point mutations, can acquire oncogenic functions, and c-Myc overexpression, due to translocations, point mutations, protein/protein interactions, or epigenetic modifications, plays a central role in cancer cell proliferation and metabolic reprogramming, particularly in colorectal cancer. In a previous study, we showed that curcumin strongly downregulated mutp53 while activating wtp53 and reduced the expression of methyltransferases such as EZH2, G9a, and MLL-1 in colon cancer cells. Based on this background, here we investigated whether the dysregulation of such methyltransferases could correlate with the effect observed on p53. We also explored whether these epigenetic changes could affect c-Myc expression in these cells. By Western blot analysis and RT-qPCR, we found that the downregulation of EZH2; G9a; and, to a lesser extent, KDM1, which was also reduced by curcumin, correlated with the decrease in mutp53 and that the reduction of EZH2 and KDM1 correlated with the activation of wtp53. Regarding c-Myc, we unveiled the occurrence of a positive feedback loop between it and MLL-1, which was inhibited by curcumin, independently of the p53 status. In conclusion, this study provides new insights into the therapeutic potential of curcumin, which involves its properties to act as an epigenetic modulator and target key molecules in colon cancer cells. Full article

(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 2nd Edition)

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Molecules, Volume 30, Issue 15 (August-1 2025) – 4 articles

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