Biomolecules

23 pages, 992 KB

Open AccessReview

The Pharmacological and Therapeutic Potential of Chrysopogon zizanioides (Vetiver): A Comprehensive Review of Its Medicinal Applications and Future Prospects

by Conjeevaram J. Gunasekar, Amin F. Majdalawieh, Imad A. Abu-Yousef and Sham A. Al Refaai

Biomolecules 2025, 15(9), 1312; https://doi.org/10.3390/biom15091312 (registering DOI) - 12 Sep 2025

Abstract

Chrysopogon zizanioides (Linn.) Nash, commonly known as vetiver, has been an integral component of traditional medicinal systems across India and Asia for centuries. The roots and essential oils of this aromatic grass have been widely utilized for their anti-inflammatory, analgesic, anticancer, antioxidant, antimicrobial, [...] Read more.

Chrysopogon zizanioides (Linn.) Nash, commonly known as vetiver, has been an integral component of traditional medicinal systems across India and Asia for centuries. The roots and essential oils of this aromatic grass have been widely utilized for their anti-inflammatory, analgesic, anticancer, antioxidant, antimicrobial, and wound-healing properties. Recent scientific investigations have provided substantial evidence supporting these traditional claims, revealing a diverse array of bioactive phytochemicals with significant pharmacological potential. Preclinical studies have demonstrated the efficacy of C. zizanioides extracts in mitigating inflammation, alleviating pain, combating microbial infections, and even exhibiting anticancer and antidiabetic effects. This review provides a comprehensive analysis of the current literature on the therapeutic properties of C. zizanioides, summarizing findings from in vitro assays, cell line studies, animal models, and available clinical studies. The bioactive constituents responsible for these pharmacological effects, including essential oil components and isolated fractions, are discussed, along with their proposed mechanisms of action. These mechanisms involve modulation of oxidative stress, inflammatory pathways, microbial proliferation, and pain perception. Additionally, current research limitations, gaps in knowledge, and future directions for investigating medicinal applications of C. zizanioides are explored. Emerging scientific evidence increasingly validates traditional claims regarding the healing properties of this versatile medicinal grass. Full article

(This article belongs to the Special Issue Natural Bioactives as Leading Molecules for Drug Development)

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25 pages, 1540 KB

Open AccessReview

Dual Perspectives on Peptide–Zinc Complexation: Highlighting Aquatic Sources While Contextualizing Other Natural Origins

by Lingyu Han, Nuo Dong, Jixin Yang and Bing Hu

Biomolecules 2025, 15(9), 1311; https://doi.org/10.3390/biom15091311 (registering DOI) - 12 Sep 2025

Abstract

Zinc is an essential mineral for the body, with chelated zinc valued for its superior absorption efficiency and bioavailability. This review systematically examines peptide–zinc interactions, covering fundamental concepts, historical evolution, current insights, clinical relevance, technological innovations, and future outlooks. It delves into chelation [...] Read more.

Zinc is an essential mineral for the body, with chelated zinc valued for its superior absorption efficiency and bioavailability. This review systematically examines peptide–zinc interactions, covering fundamental concepts, historical evolution, current insights, clinical relevance, technological innovations, and future outlooks. It delves into chelation mechanisms and structural theories, summarizes historical milestones in bioavailability research—particularly aquatic protein–zinc interactions—and details current studies on chelation efficacy and interaction dynamics. Clinical applications in nutritional supplements, therapeutic potential, and trial progress are discussed, alongside advances in analytical techniques, complex synthesis, and computational modeling. Future directions highlight emerging trends, application prospects, and challenges in bioavailability research, offering a comprehensive framework for subsequent investigations and practical implementations. Full article

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30 pages, 1228 KB

Open AccessReview

Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer’s Disease

by Amber Grewal, Simran Raikundalia, Joseph Zaia and Manveen K. Sethi

Biomolecules 2025, 15(9), 1310; https://doi.org/10.3390/biom15091310 - 11 Sep 2025

Abstract

In this review, we describe the methods used for the extraction and mass spectrometry proteomics analysis of amyloid plaques and neurofibrillary tangles (NFTs), the two primary pathological hallmarks of Alzheimer’s disease (AD). We also provide a comprehensive overview of the mass spectrometry-based studies [...] Read more.

In this review, we describe the methods used for the extraction and mass spectrometry proteomics analysis of amyloid plaques and neurofibrillary tangles (NFTs), the two primary pathological hallmarks of Alzheimer’s disease (AD). We also provide a comprehensive overview of the mass spectrometry-based studies conducted to analyze these pathological features. AD is the most prevalent form of dementia and the sixth leading cause of death in the United States. While the current treatments can alleviate early-stage memory and cognitive symptoms, they do not offer a cure. Thus, there is a pressing need to deepen our understanding of the neuropathological mechanisms underlying AD and to develop more effective therapeutics. In-depth mass spectrometry-based proteomics analyses of AD pathology—specifically, extracellular the Aβ plaques found in extracellular spaces and blood vessel walls and intraneuronal NFTs composed of the microtubule-associated protein tau—may offer molecular-level observations that contribute to the understanding of the biological context of plaque and NFT formation and support the discovery of potential biomarkers and therapeutic targets for AD. Full article

(This article belongs to the Special Issue Advances in Neuroproteomics)

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17 pages, 1556 KB

Open AccessReview

Novel Animal Models for Multiple Sclerosis: R-Ras GTPases in Myelin Pathophysiology

by Gema M. Esteban-Ortega, Gonzalo Garcia-Martin and Beatriz Cubelos

Biomolecules 2025, 15(9), 1309; https://doi.org/10.3390/biom15091309 - 11 Sep 2025

Abstract

Demyelinating diseases, such as multiple sclerosis, involve oligodendrocyte death, myelin loss, and neuronal death. These processes have been extensively studied, and a causal relationship has been demonstrated between them: destruction of oligodendrocytes results in myelin deficiency, which subsequently leads to neurodegeneration and the [...] Read more.

Demyelinating diseases, such as multiple sclerosis, involve oligodendrocyte death, myelin loss, and neuronal death. These processes have been extensively studied, and a causal relationship has been demonstrated between them: destruction of oligodendrocytes results in myelin deficiency, which subsequently leads to neurodegeneration and the consequent loss of sensory, motor, and cognitive functions. Currently, myelinopathies lack fully effective treatments. Available drugs primarily focus on controlling the immune response without directly promoting myelin regeneration or restoring neuronal functionality. Alongside these treatments, pharmaceutical research has increasingly focused on developing therapies that stimulate oligodendroglial lineage differentiation and myelin sheath regeneration. Despite these advances, the lack of suitable preclinical models has been a significant obstacle in evaluating new therapeutic compounds. In this review, we present the main animal models used in the preclinical phase for the study of myelin-related diseases and their role in the development of new therapies. In addition, we highlight the usefulness of R-Ras animal models for assessing the efficacy of compounds that promote oligodendrocyte differentiation. Full article

(This article belongs to the Special Issue Inflammatory Mechanisms and Molecular Targets in Neurological Disorders: Effects of Neuroprotective Drugs)

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32 pages, 2078 KB

Open AccessReview

Natural Compounds as Modulators of Ferroptosis: Mechanistic Insights and Therapeutic Prospects in Breast Cancer

by Haotong He, Haoyang Yu, Hefeng Zhou, Guozhen Cui and Min Shao

Biomolecules 2025, 15(9), 1308; https://doi.org/10.3390/biom15091308 - 11 Sep 2025

Abstract

Breast cancer is the most prevalent malignant tumor in women. However, its clinical management is severely hindered by three interconnected challenges that limit long-term survival: treatment resistance, metastatic dissemination, and immunological evasion. Ferroptosis, an iron-dependent form of regulated cell death, is emerging as [...] Read more.

Breast cancer is the most prevalent malignant tumor in women. However, its clinical management is severely hindered by three interconnected challenges that limit long-term survival: treatment resistance, metastatic dissemination, and immunological evasion. Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a novel strategy to overcome these obstacles. Furthermore, it demonstrates significant potential in inhibiting tumor metastasis and modifying the anti-tumor immune microenvironment, which provides a novel approach to address the core dilemma of breast cancer. Natural products have emerged as significant sources of ferroptosis inducers owing to their distinctive chemical variety, multi-target regulatory capabilities, and acceptable safety profile. Data increasingly indicates that several natural compounds can function as effective inducers or sensitizers of ferroptosis cell death. This review provides a thorough evaluation of current progress in harnessing natural ingredients to trigger ferroptosis for breast cancer treatment. It also elucidates the fundamental molecular mechanisms. Furthermore, it encapsulates therapeutic efficacy in preclinical models. Ultimately, it rigorously evaluates existing constraints and delineates potential and barriers for clinical translation. Full article

(This article belongs to the Topic Antitumor Activity of Natural Products and Related Compounds—2nd Edition)

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21 pages, 2836 KB

Open AccessArticle

Single-Vesicle Molecular Profiling by dSTORM Imaging in a Liquid Biopsy Assay Predicts Early Relapse in Colorectal Cancer

by Gabriele Raciti, Giulia Cavallaro, Raffaella Giuffrida, Cristina Grange, Loredana Leggio, Marco Catania, Nunzio Iraci, Elena Bruno, Luca Antonio Giaimi, Sofia Paola Lombardo, Giulia Chisari, Marzia Mare, Enrica Deiana, Lorenzo Memeo, Benedetta Bussolati and Stefano Forte

Biomolecules 2025, 15(9), 1307; https://doi.org/10.3390/biom15091307 - 11 Sep 2025

Abstract

Background and Objectives: Colorectal cancer (CRC) is the third most diagnosed tumor type and the second leading cause of cancer-related mortality. Despite recent improvements in the clinical management of CRC patients both before and after surgery, disease recurrence remains common, with an incidence [...] Read more.

Background and Objectives: Colorectal cancer (CRC) is the third most diagnosed tumor type and the second leading cause of cancer-related mortality. Despite recent improvements in the clinical management of CRC patients both before and after surgery, disease recurrence remains common, with an incidence of about 20–30% within 5 years. Current tissue biopsy techniques are invasive and inadequate for assessing tumor heterogeneity or capturing real-time disease dynamics. In contrast, liquid biopsy offers a promising, minimally invasive alternative. This study aimed to evaluate extracellular vesicle (EV)-associated protein markers, detected through super-resolution microscopy, as potential indicators of recurrence in CRC patients. Methods: We employed a novel liquid biopsy approach based on the super-resolution imaging (dSTORM) of specific protein markers carried by EVs isolated from the plasma of CRC patients. We analyzed combinations of both surface and intravesicular proteins, including EpCAM, PD-L1, CD81, IL-6, and Cyclin D1. Results: Specific combinations of EV-associated markers were able to distinguish patients with recurrence from those without residual disease. Additionally, we observed correlations between some marker profiles and tumor stage or lymph node involvement. No association was found with mismatch repair system status. Conclusions: To our knowledge, this is the first study to propose the use of EV-bound proteins for recurrence detection in CRC using super-resolution microscopy within a liquid biopsy framework. These findings support the potential of this approach as a non-invasive tool for CRC monitoring. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Their Roles in Cancer Progression)

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26 pages, 3890 KB

Open AccessArticle

Gene Duplication, Translocation, and Molecular Evolution of Dmrt1 and Related Sex-Determining Genes in Anurans

by Sagar S. Shinde, Paris Veltsos and Wen-Juan Ma

Biomolecules 2025, 15(9), 1306; https://doi.org/10.3390/biom15091306 - 11 Sep 2025

Abstract

Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, [...] Read more.

Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, birds, and Drosophila, most anurans (frogs and toads) maintain homomorphic sex chromosomes that exhibit a rapid turnover, even among closely related species. Master sex-determining genes evolve via gene duplication or via allelic diversification, and sex chromosome turnover is driven by gene translocation or novel mutations in the existing genes involved in the sexual developmental pathway. To uncover the mechanisms underlying the emergence of master sex-determining genes and sex chromosome turnover, we analyzed 53 published anuran genomes and one caecilian genome (>200 Mya divergence) and available transcriptomes. We asked how often master sex-determining genes arise by gene duplication, whether and how often gene translocation associates with sex chromosome turnover, and if master sex-determining genes evolve under positive selection. We find that chromosome-level synteny is remarkably conserved, with only a few fusions or fissions and no evidence for translocation of four candidate master sex-determining genes (Dmrt1, Foxl2, Bod1l, and Sox3). Only Dmrt1 duplicated in 3 out of 50 species (excluding tetraploid Xenopus), and it showed strong testis-biased expression in all 8 species with available gonadal expression data. While Dmrt1 has evolved under purifying selection, Dmrt1 duplicates exhibit elevated nonsynonymous substitution rates and tendency towards positive selection. Lineage-specific amino acid changes were observed in the conserved DM domain of Dmrt1. These results demonstrate that, in anurans, master sex-determining genes rarely arise via gene duplication, and more likely evolve via allelic diversification. Sex chromosome turnover is not associated with gene translocation and is more likely driven by mutations on genes involved in sexual developmental pathways. All candidate sex-determining genes were under strong purifying selection, with the exception of duplications which are linked to positive selection. Our results suggest future research on anuran sex determination and sex chromosome evolution should focus on identifying allelic diversification and novel mutations on genes involved in sexual developmental pathways. Full article

(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)

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18 pages, 2274 KB

Open AccessArticle

Isoniazid-Derived Hydrazones Featuring Piperazine/Piperidine Rings: Design, Synthesis, and Investigation of Antitubercular Activity

by Esma Özcan, Siva Krishna Vagolu, Rasoul Tamhaev, Christian Lherbet, Lionel Mourey, Tone Tønjum, Miyase Gözde Gündüz and Şengül Dilem Doğan

Biomolecules 2025, 15(9), 1305; https://doi.org/10.3390/biom15091305 - 11 Sep 2025

Abstract

Isoniazid (isonicotinic acid hydrazide, INH) is a key drug used to treat tuberculosis (TB), which continues to be the world’s most lethal infectious disease. Nevertheless, the efficacy of INH has diminished because of the emergence of Mycobacterium tuberculosis (Mtb) strains that [...] Read more.

Isoniazid (isonicotinic acid hydrazide, INH) is a key drug used to treat tuberculosis (TB), which continues to be the world’s most lethal infectious disease. Nevertheless, the efficacy of INH has diminished because of the emergence of Mycobacterium tuberculosis (Mtb) strains that are resistant to INH. Our goal in this study was to modify INH to reduce this significant resistance chemically. We synthesized INH-based hydrazones (IP1–IP13) through the reaction of INH with in-house obtained benzaldehydes carrying a piperidine or piperazine ring in refluxing ethanol. Upon confirmation of their proposed structures by various spectral techniques, IP1–IP13 were evaluated for their antimycobacterial capacity against Mtb H37Rv strain and INH-resistant clinical isolates with katG and inhA mutations using the Microplate Alamar Blue Assay (MABA). The compounds were additionally tested for their cytotoxicity. The obtained data indicated that the compounds with moderately increased lipophilicity compared to INH (IP7–IP13) were promising antitubercular drug candidates, exhibiting drug-like properties and negligible cytotoxicity. Out of these, IP11 (N′-(4-(4-cyclohexylpiperazin-1-yl)benzylidene)isonicotinohydrazide) emerged as the most promising derivative, demonstrating the lowest MIC values against all Mtb strains tested. Subsequently, the target molecules were evaluated for their capacity to inhibit enoyl acyl carrier protein reductase (InhA), the main target enzyme of INH. Except for IP11 demonstrating 81% InhA inhibition at a concentration of 50 μM, direct InhA inhibition was shown not to be the primary mechanism responsible for the antitubercular activity of the compounds. The binding mechanism of IP11 to InhA was analyzed through molecular docking and molecular dynamics simulations. Altogether, our research identified a novel approach to modify INH to address the challenges posed by the rising prevalence of drug-resistant Mtb strains. Full article

(This article belongs to the Special Issue Synthetic Chemistry in Drug Discovery: Novel Compounds for Antimicrobial and Antioxidant Applications)

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36 pages, 2843 KB

Open AccessReview

A Comprehensive Oncological Biomarker Framework Guiding Precision Medicine

by Reza Bayat Mokhtari, Manpreet Sambi, Faezeh Shekari, Kosar Satari, Roya Ghafoury, Neda Ashayeri, Paige Eversole, Narges Baluch, William W. Harless, Lucia Anna Muscarella, Herman Yeger, Bikul Das, Myron R. Szewczuk and Sayan Chakraborty

Biomolecules 2025, 15(9), 1304; https://doi.org/10.3390/biom15091304 - 10 Sep 2025

Abstract

Cancer remains a major cause of mortality worldwide, driving ongoing innovation in therapeutic strategies. Immunotherapy has transformed cancer care by leveraging the immune system to target tumors, but its effectiveness is limited by tumor heterogeneity, immune resistance, and unpredictable toxicities. Moreover, the absence [...] Read more.

Cancer remains a major cause of mortality worldwide, driving ongoing innovation in therapeutic strategies. Immunotherapy has transformed cancer care by leveraging the immune system to target tumors, but its effectiveness is limited by tumor heterogeneity, immune resistance, and unpredictable toxicities. Moreover, the absence of robust biomarkers to predict therapeutic response and manage adverse effects remains a significant challenge. Recent advances in biomarker discovery, including liquid biopsy technologies and gut microbiota profiling, are enhancing the precision of immunotherapy and enabling more personalized cancer management. Here, we present a Comprehensive Oncological Biomarker Framework that integrates genetic and molecular testing, imaging, histopathology, multi-omics, and liquid biopsy to generate a molecular fingerprint for each patient. This holistic approach supports individualized diagnosis, prognosis, treatment selection, and response monitoring. Incorporating emerging biomarkers, such as microbiome signatures, further refines patient stratification, guiding the optimization of therapy. By uniting molecular insights with clinical and social factors, this framework aims to address tumor heterogeneity and immune evasion, ultimately improving patient outcomes through precision oncology. Full article

(This article belongs to the Special Issue Spotlight on Hot Cancer Biological Biomarkers)

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16 pages, 1806 KB

Open AccessReview

Natural Product-Derived Drugs: Structural Insights into Their Biological Mechanisms

by Yujeong Choi, Younghyun Kim, Hye Joon Boo, Danbi Yoon, Jeong Seok Cha and Jiho Yoo

Biomolecules 2025, 15(9), 1303; https://doi.org/10.3390/biom15091303 - 10 Sep 2025

Abstract

Natural product-derived drugs represent a cornerstone of modern pharmacotherapy, with many serving as essential therapeutic agents across diverse medical conditions. Recent advances in structural biology have provided unprecedented insights into the molecular mechanisms underlying their biological activities. This review presents a comprehensive structural [...] Read more.

Natural product-derived drugs represent a cornerstone of modern pharmacotherapy, with many serving as essential therapeutic agents across diverse medical conditions. Recent advances in structural biology have provided unprecedented insights into the molecular mechanisms underlying their biological activities. This review presents a comprehensive structural analysis of five representative natural product-derived drugs: digoxin, simvastatin, morphine, paclitaxel, and penicillin. Through an examination of high-resolution crystal structures and cryo-electron microscopy (cryo-EM) data, we elucidate how these compounds interact with their respective protein targets and modulate biological functions. The structural data reveal diverse binding mechanisms—ranging from competitive inhibition and covalent modification to allosteric modulation via conformational selection and induced fit—demonstrating how natural products achieve their therapeutic effects through precise molecular recognition. These structural insights provide a molecular foundation for understanding natural product pharmacology and offer valuable guidance for structure-based drug design approaches in developing next-generation therapeutics. Full article

(This article belongs to the Special Issue Biomolecules and Their Impact on Biology and Translational Applications: Celebrating the Pioneering Work of Prof. Ho Jeong Kwon: 2nd Edition)

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21 pages, 2694 KB

Open AccessArticle

Nature’s Synergy: Cellular and Molecular Evaluation of Snail Slime and Its Principal Component, Glycolic Acid, on Keratinocytes, with Preliminary Evidence from Endothelial Cells

by Muhammad Rashad, Alessia Ricci, Serena Pilato, Amelia Cataldi, Marwa Balaha and Susi Zara

Biomolecules 2025, 15(9), 1302; https://doi.org/10.3390/biom15091302 - 10 Sep 2025

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Abstract

Snail slime (SS) is a natural secretion rich in bioactive components such as glycoproteins, hyaluronic acid, glycolic acid (GA), and antimicrobial peptides. GA, a key component of SS, is known for its exfoliative properties. This study investigates SS’s effects on keratinocytes (HaCaT) and [...] Read more.

Snail slime (SS) is a natural secretion rich in bioactive components such as glycoproteins, hyaluronic acid, glycolic acid (GA), and antimicrobial peptides. GA, a key component of SS, is known for its exfoliative properties. This study investigates SS’s effects on keratinocytes (HaCaT) and endothelial cells (ECs), comparing its properties to those of GA. HaCaT cell viability and cytotoxicity, ROS release, and inflammation-related signaling (PI3K/Akt/NF-κB and COX-2 gene expression) were assessed. Extracellular matrix (ECM) remodeling was evaluated by gene expression of MMPs. In ECs, a preliminary evaluation of SS’s effect was conducted in terms of cell viability and migration. Results demonstrated that SS is well tolerated by keratinocytes whereas GA exhibits cytotoxicity, suggesting that SS’s natural composition mitigates GA’s adverse effects. SS induced a controlled, brief inflammatory response, via the PI3K/Akt/NF-κB pathway, unlike GA, responsible for stronger and sustained pro-inflammatory events. Additionally, SS, through the upregulation of MMPs, contributes to ECM remodeling. In ECs, SS preserves viability and also enhances migration, thus supporting wound healing. These findings highlight SS’s ability to balance pro-inflammatory events, making it a promising candidate for advanced dermatological applications, underscoring SS’s potential in modulating key cellular signaling pathways, and supporting its future therapeutic prospects in wound healing. Full article

(This article belongs to the Special Issue Design and Synthesis of Bioactive Compounds for Therapeutic Applications)

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18 pages, 3328 KB

Open AccessArticle

In Vivo Anti-Inflammatory Activity of Lipids Extracted from the Most Abundant Cyanobacterial Strains of the Therapeutic Euganean Thermal Muds

by Micol Caichiolo, Giuliana d’Ippolito, Angela Grazioso, Chiara Rampazzo, Angelica Marchetto, Fabrizio Caldara, Luisa Dalla Valle and Nicoletta La Rocca

Biomolecules 2025, 15(9), 1301; https://doi.org/10.3390/biom15091301 - 10 Sep 2025

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Abstract

Cyanobacteria are a natural source of bioactive compounds increasingly recognized for their anti-inflammatory properties. In the Euganean Thermal District (Italy), thermal muds, used to cure arthro-rheumatic diseases, are prepared using natural clay and thermal water, resulting in a mature mud characterized by a [...] Read more.

Cyanobacteria are a natural source of bioactive compounds increasingly recognized for their anti-inflammatory properties. In the Euganean Thermal District (Italy), thermal muds, used to cure arthro-rheumatic diseases, are prepared using natural clay and thermal water, resulting in a mature mud characterized by a complex microbial biofilm dominated by Cyanobacteria. Among these, Phormidium sp. ETS-05 has been shown to contribute to the therapeutic properties of the mud, mainly through the production of bioactive compounds such as exopolysaccharides (EPS) and glycoglycerolipids (GLs). In contrast, the role of biomolecules from Thermospirulina andreolii ETS-09 and Kovacikia euganea ETS-13, also abundant in mature muds but at higher maturation temperatures, has not been investigated. This study focuses on the lipid profiles of these cyanobacteria, cultivated under temperature conditions that mimic their natural environment and that are different for the three species. Lipid extracts were analyzed for GLs classes and fatty acid composition, and their anti-inflammatory potential was assessed in vivo using a zebrafish inflammation model. All extracts showed anti-inflammatory activity with Phormidium sp. ETS-05 displaying the highest lipid content and the most rapid and potent beneficial effect, likely due to the specific composition of its GLs, presenting the greatest abundance of polyunsaturated fatty acids. These findings provide new insights into the biological basis of the therapeutic effects of Euganean muds and emphasize the importance of maturation conditions for cyanobacterial growth and bioactive lipid production. Full article

(This article belongs to the Special Issue Recent Advances in Bioactive Compounds from Microalgae)

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17 pages, 1426 KB

Open AccessArticle

Cerebrospinal Fluid Erythrocyte Burden Amplifies the Impact of PTAU on Entorhinal Degeneration in Alzheimer’s Disease

by Rafail C. Christodoulou, Georgios Vamvouras, Vasileia Petrou, Platon S. Papageorgiou, Rafael Pitsillos, Ludwing Rivera, Evros Vassiliou, Sokratis G. Papageorgiou, Elena E. Solomou and for the Alzheimer’s Disease Neuroimaging Initiative

Biomolecules 2025, 15(9), 1300; https://doi.org/10.3390/biom15091300 - 10 Sep 2025

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Abstract

Background: Alzheimer’s disease (AD) involves ongoing neurodegeneration, with phosphorylated tau (PTAU) intracellular accumulation closely associated with cortical shrinking. However, not everyone with high PTAU levels shows the same degree of neurodegeneration, implying that other biological stress factors might influence tau’s harmful effects. This [...] Read more.

Background: Alzheimer’s disease (AD) involves ongoing neurodegeneration, with phosphorylated tau (PTAU) intracellular accumulation closely associated with cortical shrinking. However, not everyone with high PTAU levels shows the same degree of neurodegeneration, implying that other biological stress factors might influence tau’s harmful effects. This research explores whether cerebrospinal fluid erythrocyte burden (CTRED), a marker indicating vascular–CSF barrier disruption and heme toxicity, affects the link between PTAU181 levels and entorhinal cortex atrophy in AD. Methods: We examined 25 observations from 18 patients with AD using a linear mixed effects model. The dependent variable was entorhinal cortex volume, with fixed effects for PTAU, CTRED, and their interaction. Random intercepts accounted for variability within subjects. A cognitively normal (CN) control group was included for comparison. Results: CTRED is significantly associated with reduced entorhinal volume (p = 0.005). A notable interaction between CTRED and PTAU was also found (p = 0.004), suggesting that higher CTRED enhances PTAU’s atrophic effects. PTAU alone was not a significant predictor. No significant effects were observed in the CN group, which supports the specificity of the disease. Conclusions: CTRED alters the neurotoxic impact of PTAU on the entorhinal cortex in AD, supporting a multi-hit model of degeneration that involves tau pathology and erythrocyte-derived stress. These findings emphasize the clinical importance of vascular–CSF biomarkers in predicting neurodegeneration and guiding targeted treatments. Full article

(This article belongs to the Special Issue Artificial Intelligence (AI) in Biomedicine: 2nd Edition)

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17 pages, 1566 KB

Open AccessCommunication

Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans

by Alexander Morin, Michael Christie, Eve Damiano and Maria L. Maccecchini

Biomolecules 2025, 15(9), 1299; https://doi.org/10.3390/biom15091299 - 10 Sep 2025

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Abstract

Buntanetap is an orally bioavailable small molecule that has been shown to improve cognitive function in patients with Alzheimer’s and Parkinson’s diseases and holds promise for use in other neurodegenerative conditions. Until now, a crystalline anhydrate (Form A) has been used in preclinical [...] Read more.

Buntanetap is an orally bioavailable small molecule that has been shown to improve cognitive function in patients with Alzheimer’s and Parkinson’s diseases and holds promise for use in other neurodegenerative conditions. Until now, a crystalline anhydrate (Form A) has been used in preclinical and clinical studies. However, a novel dihydrate crystal (Form B) was recently discovered, offering improved solid-state stability without compromising its absorption, systemic exposure, and metabolism. We sought to evaluate the pharmacokinetic (PK) profile of Form B and compare it to the well-characterized PK profile of Form A in a series of studies conducted in mice, dogs, and humans. Our data revealed that although the two forms are distinct and do not interconvert, they exhibit comparable PK profiles both within and across species. Consistent with previous reports, Form A and Form B alike reached fast peak plasma concentrations (<2 h), demonstrated efficient partitioning into brain tissue, and were fully cleared by 12 h post-dose. Furthermore, metabolic profiling showed that both forms produced identical PK profiles for the primary metabolites, N1- and N8-norbuntanetap, confirming that Form B retains the established metabolic characteristics of Form A. These findings support the continued development of Form B for future clinical use, as it combines enhanced solid-state stability with a preserved PK profile essential for buntanetap’s therapeutic efficacy. Full article

(This article belongs to the Section Molecular Medicine)

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18 pages, 2237 KB

Open AccessArticle

N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin T in Stable Renal Transplant Recipients and All-Cause Mortality, Cardiovascular, and Renal Events

by Zbigniew Heleniak, Marcel G. Naik, Georgios Eleftheriadis, Tomasz Madej, Fabian Halleck, Alicja Dębska-Ślizień and Klemens Budde

Biomolecules 2025, 15(9), 1298; https://doi.org/10.3390/biom15091298 - 9 Sep 2025

Viewed by 190

Abstract

Introduction: In renal transplant recipients (RTRs), kidney graft failure and cardiovascular (CV) disease are prevalent and associated with mortality. Objectives: The objective of the study was to evaluate biomarkers, (cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)), to identify RTRs who [...] Read more.

Introduction: In renal transplant recipients (RTRs), kidney graft failure and cardiovascular (CV) disease are prevalent and associated with mortality. Objectives: The objective of the study was to evaluate biomarkers, (cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)), to identify RTRs who are at greater risk of death, CV event, and graft renal survival. Patients and methods: A total of 342 stable RTRs were enrolled in this study, with a median follow-up time of 54 months. The probability of death, CV event, and renal graft survival were calculated using Kaplan–Meier analysis for the group defined by cTnT and NT-proBNP levels above the cutoff values. Results: The probability of death for troponin T level above the cut-off was 23% and for NT-proBNP 29%. For CV events the probability for troponin T was 20% and for NT-proBNP it was 21%. Troponin T concentrations above the cutoff point suggested a 25% probability of death-censored graft survival. For NT-proBNP, it was 26%. The probability of overall graft survival was 38% for patients with higher troponin T levels, and 40% for NT proBNP. Conclusions: These data suggest that cTnT and NT-proBNP could potentially identify patients at high risk for death, CV event, and graft survival. Full article

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14 pages, 791 KB

Open AccessArticle

Assessment of Cardiorenal Involvement in Systemic Sclerosis Patients

by Chiara Pellicano, Giancarlo D’Ippolito, Annalisa Villa, Ottavio Martellucci, Umberto Basile, Valeria Carnazzo, Valerio Basile, Edoardo Rosato, Mariapaola Marino and Antonietta Gigante

Biomolecules 2025, 15(9), 1297; https://doi.org/10.3390/biom15091297 - 9 Sep 2025

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Abstract

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart [...] Read more.

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiorenal Syndrome)

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18 pages, 1595 KB

Open AccessArticle

Blood Plasma Lipid Alterations Differentiating Psychotic and Affective Disorder Patients

by Anastasia Golubova, Elena Stekolshchikova, Anna Gareeva, Inessa Akhmerova, Ilgiz Timerbulatov, Valeria Zakurazhnaya, Daria Riabinina, Alexander Reznik, Anna Morozova, Denis Andreyuk, Georgiy Kostyuk, Daria Petrova, Anna Serkina, Philipp Khaitovich and Anna Tkachev

Biomolecules 2025, 15(9), 1296; https://doi.org/10.3390/biom15091296 - 9 Sep 2025

Viewed by 202

Abstract

Psychotic and affective disorders, including schizophrenia (SCZ) and depression (MDD), affect millions of people globally. The overlapping symptoms of these diseases and the lack of objective diagnostic tools could lead to misdiagnosis. Recent studies suggest that the analysis of plasma lipid levels may [...] Read more.

Psychotic and affective disorders, including schizophrenia (SCZ) and depression (MDD), affect millions of people globally. The overlapping symptoms of these diseases and the lack of objective diagnostic tools could lead to misdiagnosis. Recent studies suggest that the analysis of plasma lipid levels may help to develop new diagnostic tools. In this study, we investigated the plasma lipidome of psychiatric patients and healthy controls to identify disease-specific lipid species. Using untargeted mass spectrometry, we profiled blood plasma lipids from 416 patients with common psychotic and affective disorders and 272 healthy individuals from two different cohorts. We observed lipidome alterations in SCZ and MDD consistent with earlier findings. In total, 144 lipids showed significant changes, with 107 of them being concordant across both disorders, and 37 being discordant. Lipids that differentiated SCZ from MDD were mainly triacylglycerols with polyunsaturated fatty acid residues decreased in MDD. In an additional group of 111 patients with bipolar, schizotypal, and schizoaffective disorders, these lipid markers suggested a trend toward separating psychotic and affective disorders. Furthermore, a logistic regression model trained on lipid data distinguished SCZ from MDD with an ROC AUC of 0.83. Taken together, these results suggest that blood lipid profiling may aid in the objective differentiation of psychotic and affective disorders. Full article

(This article belongs to the Section Lipids)

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18 pages, 2244 KB

Open AccessArticle

Metabolic Adaptations Determine the Evolutionary Trajectory of TOR Signaling in Diverse Eukaryotes

by Kyle Johnson, Dellaraam Pourkeramati, Ian Korf and Ted Powers

Biomolecules 2025, 15(9), 1295; https://doi.org/10.3390/biom15091295 - 8 Sep 2025

Viewed by 309

Abstract

Eukaryotes use diverse nutrient acquisition strategies, including autotrophy, heterotrophy, mixotrophy, and symbiosis, which shape the evolution of cell regulatory networks. The Target of Rapamycin (TOR) kinase is a conserved growth regulator that in most species functions within two complexes, TORC1 and TORC2. TORC1 [...] Read more.

Eukaryotes use diverse nutrient acquisition strategies, including autotrophy, heterotrophy, mixotrophy, and symbiosis, which shape the evolution of cell regulatory networks. The Target of Rapamycin (TOR) kinase is a conserved growth regulator that in most species functions within two complexes, TORC1 and TORC2. TORC1 is broadly conserved and uniquely sensitive to rapamycin, whereas the evolutionary distribution of TORC2 is less well-defined. We built a sensitive hidden Markov model (HMM)-based pipeline to survey core TORC1 and TORC2 components across more than 800 sequenced eukaryotic genomes spanning multiple major supergroups. Both complexes are present in early-branching lineages, consistent with their presence in the last eukaryotic common ancestor, followed by multiple lineage-specific losses of TORC2 and, more rarely, TORC1. A striking pattern emerges in which TORC2 is uniformly absent from photosynthetic autotrophs derived from primary endosymbiosis and frequently lost in those derived from secondary or tertiary events. In contrast, TORC2 is consistently retained in mixotrophs, which obtain carbon from both photosynthesis and environmental uptake, and in free-living obligate heterotrophs. These findings suggest that TORC2 supports heterotrophic metabolism and is often dispensable under strict autotrophy. Our results provide a framework for the evolutionary divergence of TOR signaling and highlight metabolic and ecological pressures that shape TOR complex retention across eukaryotes. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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14 pages, 570 KB

Open AccessArticle

In Vitro Analysis of an Alkalihalobacillus clausii Spore-Based Probiotic Formulation Clarifies the Mechanisms Underlying Its Beneficial Properties

by Diletta Mazzantini, Marco Calvigioni, Francesco Celandroni, Alessandro Saba and Emilia Ghelardi

Biomolecules 2025, 15(9), 1294; https://doi.org/10.3390/biom15091294 - 8 Sep 2025

Viewed by 266

Abstract

Probiotics are microorganisms with recognized beneficial properties that are used to improve host health. In particular, probiotics administered as spores, such as those belonging to the genera Bacillus and Alkalihalobacillus, are attracting great interest due to their high tolerance to gastrointestinal conditions. [...] Read more.

Probiotics are microorganisms with recognized beneficial properties that are used to improve host health. In particular, probiotics administered as spores, such as those belonging to the genera Bacillus and Alkalihalobacillus, are attracting great interest due to their high tolerance to gastrointestinal conditions. This in vitro study aimed to assess the probiotic attributes potentially contributing to the in vivo beneficial effects of a commercial spore-based probiotic formulation composed of four Alkalihalobacillus clausii strains. The tolerance and survival of the spores from the formulation in simulated gastrointestinal fluids, as well as their germination rate and adhesion to mucins, were analyzed. Furthermore, metabolic properties of spore-derived vegetative cells were assessed, including lactose degradation and biosynthesis of antioxidant enzymes (catalase and superoxide dismutase), group B vitamins (B₂, B₈, B₉, and B₁₂), short-chain fatty acids (acetate, propionate, and butyrate), and D-lactate. A. clausii spores were shown to survive in artificial gastric juice, adhere to mucins and germinate in vitro, and replicate in simulated intestinal fluid, suggesting their potential resilience in the gastrointestinal tract, where they can exert beneficial effects after germination. A. clausii was also able to produce beneficial enzymes and metabolites, including β-galactosidase, catalase, superoxide dismutase, group B vitamins, and short-chain fatty acids, but it was unable to produce D-lactic acid. Our findings highlight the probiotic properties and potential of such A. clausii strains in both their spore and vegetative forms, reinforcing the clinical relevance of this multi-strain spore-based formulation for enhancing intestinal health. Full article

(This article belongs to the Special Issue Probiotics and Their Metabolites, 2nd Edition)

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13 pages, 2448 KB

Open AccessArticle

Differentiation of Dmrt1 Z and W Homologs Occurred Independently in Two Gekko hokouensis Populations

by Momoka Senga, Nao Kaneko, Yoichi Matsuda and Kazumi Matsubara

Biomolecules 2025, 15(9), 1293; https://doi.org/10.3390/biom15091293 - 8 Sep 2025

Viewed by 319

Abstract

Gekko hokouensis is a gecko species widely distributed across East Asia. Although most of the Japanese populations possess ZW sex chromosomes (female heterogamety), the degree of sex chromosome differentiation varies among populations. The gene encoding for Dmrt1, a transcription factor involved in testis [...] Read more.

Gekko hokouensis is a gecko species widely distributed across East Asia. Although most of the Japanese populations possess ZW sex chromosomes (female heterogamety), the degree of sex chromosome differentiation varies among populations. The gene encoding for Dmrt1, a transcription factor involved in testis development in vertebrates, is located on the Z and W sex chromosomes of this species and is therefore a candidate of the sex-determining gene. In this study, we investigated the gene structure of the Z and W homologs of Dmrt1 in two populations of Gekko hokouensis from the Ishigaki Island and Okinawa Island. In the Ishigaki population, the ZW chromosome pair is morphologically undifferentiated, whereas in the Okinawa population the ZW pair is heteromorphic. In the Okinawa population, promoter and exon sequences were nearly identical between the Z and W homologs, and no non-synonymous substitution was detected. In contrast, the W homolog in the Ishigaki population exhibited 42 bp and 12 bp deletions in exon 2. The predicted three-dimensional protein structure revealed a rearrangement of the C-terminal region in the W homolog that may interfere with target site binding. These results indicate that differentiation between Z and W homologs of Dmrt1 has occurred independently in each population. Our findings highlight the diversity of sex chromosome evolution and sex-determining mechanisms even within a single species. Full article

(This article belongs to the Special Issue Molecular Insights into Sex and Evolution)

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36 pages, 3121 KB

Open AccessReview

The Emerging Role of Mitochondrial Dysfunction in Thyroid Cancer: Mediating Tumor Progression, Drug Resistance, and Reshaping of the Immune Microenvironment

by Yating Zhang, Hengtong Han, Tingting Zhang, Tianying Zhang, Libin Ma, Ze Yang and Yongxun Zhao

Biomolecules 2025, 15(9), 1292; https://doi.org/10.3390/biom15091292 - 8 Sep 2025

Viewed by 431

Abstract

As the hub of energy metabolism and the cell’s fate arbiter, mitochondria are essential for preserving cellular homeostasis and converting it from pathological states. Therefore, through mechanisms that drive metabolic reprogramming, oxidative stress, and apoptosis resistance, mitochondrial dysfunction (including mitochondrial DNA mutations, mitochondrial [...] Read more.

As the hub of energy metabolism and the cell’s fate arbiter, mitochondria are essential for preserving cellular homeostasis and converting it from pathological states. Therefore, through mechanisms that drive metabolic reprogramming, oxidative stress, and apoptosis resistance, mitochondrial dysfunction (including mitochondrial DNA mutations, mitochondrial dynamics imbalance, mitochondrial autophagy abnormalities, mitochondrial permeability abnormalities, and metabolic disorder) can promote the progression of thyroid cancer (TC), resistance to treatment, and reshaping of the immune microenvironment. This article reviews the molecular mechanisms and characteristic manifestations of mitochondrial dysfunction in TC. It focuses on providing a summary of the main strategies currently used to target the mitochondria, such as dietary intervention and targeted medications like curcumin, as well as the clinical translational value of these medications when used in conjunction with current targeted therapies for TC and radioactive iodine (RAI) therapy in patients with advanced or RAI-refractory TC who rely on targeted therapies. The application prospects and existing challenges of emerging therapeutic methods, such as mitochondrial transplantation, are also discussed in depth, aiming to provide new perspectives for revealing the molecular mechanisms by which mitochondrial dysfunction drives the progression of TC, drug resistance, and the reshaping of its immune microenvironment, as well as providing new diagnostic and therapeutic strategies for patients with advanced or RAI-refractory TC who are reliant on targeted therapies. Full article

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8 pages, 511 KB

Open AccessPerspective

Structure and Function of PML Nuclear Bodies: A Brief Overview of Key Cellular Roles

by Karolina Dorosz, Lidia Majewska and Jacek Kijowski

Biomolecules 2025, 15(9), 1291; https://doi.org/10.3390/biom15091291 - 8 Sep 2025

Viewed by 321

Abstract

Promyelocytic leukemia nuclear bodies (PML-NBs) are dynamic membrane-less organelles (MLOs) located in the nucleus that serve as regulatory hubs for multiple cellular processes. This review examines current understanding of PML-NB structure, assembly mechanisms, and their diverse functional roles. We discuss how PML-NBs interact [...] Read more.

Promyelocytic leukemia nuclear bodies (PML-NBs) are dynamic membrane-less organelles (MLOs) located in the nucleus that serve as regulatory hubs for multiple cellular processes. This review examines current understanding of PML-NB structure, assembly mechanisms, and their diverse functional roles. We discuss how PML-NBs interact with chromatin to influence gene expression, regulate transcription factors, and participate in protein quality control. The review highlights their critical functions in tumor suppression, particularly in acute promyelocytic leukemia, and their role in intrinsic antiviral defense against various pathogens. Despite significant advances in the field, key questions remain regarding the mechanistic triggers of PML-NB formation and their common roles across different pathologies. Further elucidation of these aspects may provide valuable insights for developing therapeutic approaches targeting the PML-NB axis in disease treatment. Full article

(This article belongs to the Section Molecular Biology)

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22 pages, 1006 KB

Open AccessReview

Translating Alzheimer’s Disease Mechanisms into Therapeutic Opportunities

by Jiejia Li, Liyun Wang, Xiaodan Zhang, Jianhua Shi, Yizhun Zhu, Han Wang, Xiangyang Zhu, Qing Zhu and Jia-Lie Luo

Biomolecules 2025, 15(9), 1290; https://doi.org/10.3390/biom15091290 - 8 Sep 2025

Viewed by 419

Abstract

Alzheimer’s disease (AD), characterized by progressive cognitive decline and functional impairment, is the most prevalent cause of dementia, and it poses a significant socioeconomic and caregiving burden on patients, families, and healthcare systems. Notwithstanding comprehensive research, the precise causes underlying AD remain ambiguous. [...] Read more.

Alzheimer’s disease (AD), characterized by progressive cognitive decline and functional impairment, is the most prevalent cause of dementia, and it poses a significant socioeconomic and caregiving burden on patients, families, and healthcare systems. Notwithstanding comprehensive research, the precise causes underlying AD remain ambiguous. Evidence increasingly indicates that AD is a multifactorial and heterogeneous disease involving a mix of genetic and environmental factors. The amyloid-cascade hypothesis, neuroinflammation and immunity, vascular pathology, and oxidative stress all fulfill significant functions in the onset and development of AD. This review primarily examines the critical pathogenesis, key biomarkers, and novel therapeutic strategies of Alzheimer’s disease to inform future research directions. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Novel Therapeutic Approaches of Neurodegenerative Diseases)

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31 pages, 18432 KB

Open AccessArticle

Elderberry-Based Multifunctional Prebiotic Systems Prepared via Spray Drying

by Anna Gościniak, Lidia Tajber, Piotr Szulc, Andrzej Miklaszewski, Tomasz M. Karpiński and Judyta Cielecka-Piontek

Biomolecules 2025, 15(9), 1289; https://doi.org/10.3390/biom15091289 - 7 Sep 2025

Viewed by 403

Abstract

Elderberry (Sambucus nigra L.) is recognized as a rich source of anthocyanins and other bioactives with antioxidant and antidiabetic potential, and is increasingly explored as a functional ingredient in nutraceuticals. However, cultivar-dependent variability can strongly influence chemical composition and bioactivity, underscoring the [...] Read more.

Elderberry (Sambucus nigra L.) is recognized as a rich source of anthocyanins and other bioactives with antioxidant and antidiabetic potential, and is increasingly explored as a functional ingredient in nutraceuticals. However, cultivar-dependent variability can strongly influence chemical composition and bioactivity, underscoring the need for careful selection of plant material prior to formulation. In the present study, twelve genotypes of elderberry were compared in terms of total polyphenols, antioxidant activity, and antiglycation potential. Based on the overall profile, ‘Samyl 1’ was advanced to formulation trials. Spray-dried carrier systems were produced using galactooligosaccharides (GOS) or chitooligosaccharides (COS), with or without colloidal silica. GOS-based powders retained anthocyanins at levels approaching theoretical values and exhibited superior thermal stability, as evidenced by differential scanning calorimetry, thermogravimetric analysis, and degradation-kinetic modeling, whereas COS matrices provided less effective stabilization. Incorporation of silica significantly enhanced technological properties, improving recovery, reducing agglomeration, and increasing flowability, without compromising anthocyanin content. All powders displayed low moisture (2.5–7.1%), favorable morphology, and preserved functional activity, aligning with stability requirements for shelf-stable plant extracts. Overall, the study demonstrates that strategic cultivar selection combined with GOS–silica carrier systems enables the production of stable elderberry powders that maintain high anthocyanin content and bioactivity. Such multifunctional ingredients couple prebiotic functionality with efficient delivery of polyphenols, highlighting their potential in nutraceutical and pharmaceutical formulations. Full article

(This article belongs to the Special Issue Advances in Pharmacognosy and Phytochemistry: From Molecular to Pre-Clinical Insights)

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19 pages, 3691 KB

Open AccessArticle

Postmortem Stability Analysis of Lipids and Polar Metabolites in Human, Rat, and Mouse Brains

by Marina Zavolskova, Dmitry Senko, Olga Bukato, Sergey Troshin, Elena Stekolshchikova, Mark Kachanovski, Anna Akulova, Maria Afonina, Olga Efimova, Daria Petrova, Maria Osetrova and Philipp Khaitovich

Biomolecules 2025, 15(9), 1288; https://doi.org/10.3390/biom15091288 - 5 Sep 2025

Viewed by 399

Abstract

Lipids and polar metabolites are emerging as promising indicators of the brain’s molecular phenotype in both clinical and fundamental research. However, the impact of postmortem delay on these compounds, unavoidable in human brain studies, remains insufficiently understood. In this study, we examined the [...] Read more.

Lipids and polar metabolites are emerging as promising indicators of the brain’s molecular phenotype in both clinical and fundamental research. However, the impact of postmortem delay on these compounds, unavoidable in human brain studies, remains insufficiently understood. In this study, we examined the postmortem stability of lipids and polar metabolites over a 48-h interval in the brains of three species: humans, rats, and mice. We show that the abundance levels of 23% of the 867 studied lipids and 75% of the 104 studied polar metabolites were affected significantly by postmortem delay in at least one species. The postmortem effects correlated positively and significantly among the species, while showing an approximately tenfold slower rate in humans compared to rodents. The only exception to the postmortem rates deceleration was a group of oxidized fatty acids, which accumulated at similar speed in both humans and rodents. These findings provide valuable insights for improving reproducibility and refining the interpretation of human and rodent brain lipidome and metabolome data in future studies. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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11 pages, 201 KB

Open AccessArticle

Human Stem Cell-Based Embryo Models in Implantation Research: Regulation, Consistency and Potential

by Søren Holm

Biomolecules 2025, 15(9), 1287; https://doi.org/10.3390/biom15091287 - 5 Sep 2025

Viewed by 350

Abstract

The use of human stem cell-based embryo models (hSCBEM) in implantation research is developing rapidly. This raises regulatory and ethical issues as these models become more complex and get closer to morphological and functional identity with human embryos. This paper provides an analysis [...] Read more.

The use of human stem cell-based embryo models (hSCBEM) in implantation research is developing rapidly. This raises regulatory and ethical issues as these models become more complex and get closer to morphological and functional identity with human embryos. This paper provides an analysis of two possible approaches to resolving the regulatory issues. The first approach is to try to achieve consistency with current regulation of embryo research, and the second approach is to elaborate the regulation of hSCBEMs based on their developmental potential. It is shown that both approaches are problematic. The consistency approach is problematic because the current regulation of embryo research is best understood as being the result of a historical, political compromise in most jurisdictions. And the approach based on assessment of developmental potential is problematic because of unavoidable epistemic uncertainty about the potential of a new hSCBEM, and because of problems in determining what constitutes a particular model, and what changes to a model makes it into a different model. Full article

(This article belongs to the Special Issue Embryo Implantation: New Molecular Insights in Endometrial Receptivity, Trophoblast Invasion and Signaling)

18 pages, 1009 KB

Open AccessReview

Optogenetics: A Novel Therapeutic Avenue for Age-Related Macular Degeneration

by Pier Luigi Grenga, Chiara Ciancimino, Alessandro Meduri and Serena Fragiotta

Biomolecules 2025, 15(9), 1286; https://doi.org/10.3390/biom15091286 - 5 Sep 2025

Viewed by 479

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors in the macula. Current treatment options primarily focus on slowing disease progression in neovascular AMD, while [...] Read more.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors in the macula. Current treatment options primarily focus on slowing disease progression in neovascular AMD, while effective therapies for dry AMD remain limited. Optogenetics, a revolutionary technique utilizing light-sensitive proteins (opsins) to control the activity of genetically targeted cells, has emerged as a promising therapeutic strategy for restoring vision in retinal degenerative diseases. In retinal disease models, adeno-associated viruses (AAVs) serve as delivery vectors via intravitreal or subretinal injections. This review explores the principles of optogenetics, its application in preclinical AMD models, and the potential for clinical translation of this approach. We discuss the various optogenetic tools, delivery methods, and the challenges and future directions in harnessing this technology to combat AMD-related vision loss. Full article

(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration: From Pathogenesis to Therapeutic Strategies)

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31 pages, 2529 KB

Open AccessArticle

Synthesis and Bioevaluation of Chalcones as Broad-Spectrum Antiviral Compounds Against Single-Stranded RNA Viruses

by Lorael K. M. Kirton, Nasser N. Yousef, Griffith D. Parks and Otto Phanstiel IV

Biomolecules 2025, 15(9), 1285; https://doi.org/10.3390/biom15091285 - 5 Sep 2025

Viewed by 389

Abstract

Chalcones are flavonoid compounds containing an α,β-unsaturated ketone core that are often found in plants and have diverse biological activities including antiviral activity. For example, chalcone 8o was previously shown to have antiviral activity against human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV); [...] Read more.

Chalcones are flavonoid compounds containing an α,β-unsaturated ketone core that are often found in plants and have diverse biological activities including antiviral activity. For example, chalcone 8o was previously shown to have antiviral activity against human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV); two viruses that use a nuclear phase to complete their growth cycle. Here, we synthesized ten new derivatives of 8o and tested them for antiviral activity against four RNA viruses that replicate exclusively in the cytoplasm, including prototype members of the paramyxovirus, flavivirus, bunyavirus, and coronavirus families. For example, chalcones 8o and 8p showed potent inhibition of PIV5 replication with minimal cytotoxicity in human fibroblast cultures. Time-of-addition studies showed that these chalcones inhibit an early stage of viral replication and prevent viral spread through cell cultures. Most importantly, our top performing chalcones showed potent in vitro antiviral activity against Zika virus, La Crosse Virus, and the coronavirus OC43. These studies offer mechanistic insight into chalcone-mediated inhibition of viral replication, demonstrate the influence of functional group changes of chalcone scaffolds on their efficacy as antivirals, and support the development of chalcones as broad-spectrum antiviral compounds. Full article

(This article belongs to the Section Natural and Bio-derived Molecules)

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34 pages, 2980 KB

Open AccessReview

The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe?

by Dimitris Kounatidis, Natalia G. Vallianou, Eleni Rebelos, Kalliopi Vallianou, Evanthia Diakoumopoulou, Konstantinos Makrilakis and Nikolaos Tentolouris

Biomolecules 2025, 15(9), 1284; https://doi.org/10.3390/biom15091284 - 5 Sep 2025

Viewed by 595

Abstract

Erectile dysfunction (ED) is a common yet frequently underrecognized microvascular complication of diabetes, affecting up to three out of four individuals. Key contributing factors include advancing age, long-standing disease duration, and suboptimal glycemic control, as well as insulin resistance and androgen deficiency—the latter [...] Read more.

Erectile dysfunction (ED) is a common yet frequently underrecognized microvascular complication of diabetes, affecting up to three out of four individuals. Key contributing factors include advancing age, long-standing disease duration, and suboptimal glycemic control, as well as insulin resistance and androgen deficiency—the latter being particularly common in men with type 2 diabetes (T2D) and obesity. While numerous studies have investigated the effects of various antidiabetic therapies on diabetes-related ED, the results remain inconsistent, limiting definitive conclusions. In recent years, increasing attention has focused on a novel class of antidiabetic medications, namely glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These agents have become central to the treatment of T2D due to their potent glucose-lowering properties and well-documented benefits on cardiovascular outcomes, and weight loss. Given these pleiotropic effects, GLP-1 RAs have been presumed to positively influence erectile function—a hypothesis supported by a growing body of experimental and clinical research. However, preliminary reports have also raised concerns about a possible association between GLP-1 RA use and ED. This narrative review aims to synthesize current evidence regarding the impact of GLP-1 RAs on erectile function, providing a platform for future research in this evolving field. Full article

(This article belongs to the Collection Feature Papers in Biological Factors)

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18 pages, 4199 KB

Open AccessArticle

In Situ Synthesis of Bacterial Cellulose-Supported CoAl-Layered Double Hydroxide as a Peroxymonosulfate Activator for Enhancing the Removal of Tetracycline

by Xiuzhi Bai, Yongsheng Du, Zhongxiang Liu, Jing Cheng, Jie Yang and Ying Li

Biomolecules 2025, 15(9), 1283; https://doi.org/10.3390/biom15091283 - 5 Sep 2025

Viewed by 340

Abstract

This study employed the hydrothermal coprecipitation method to grow CoAl-layered double hydroxide (LDH) onto bacterial cellulose (BC) in situ, successfully preparing the CoAl-LDH@BC composite. This composite was then used to activate peroxymonosulfate (PMS) for tetracycline (TC) degradation. According to the results, the CoAl-LDH@BC/PMS [...] Read more.

This study employed the hydrothermal coprecipitation method to grow CoAl-layered double hydroxide (LDH) onto bacterial cellulose (BC) in situ, successfully preparing the CoAl-LDH@BC composite. This composite was then used to activate peroxymonosulfate (PMS) for tetracycline (TC) degradation. According to the results, the CoAl-LDH@BC/PMS system demonstrated a remarkable removal efficiency of 99.9% for TC within 15 min. Moreover, the influencing factors of catalyst dosage, PMS dosage, TC concentration, reaction temperature, initial pH, and inorganic ions were evaluated. Notably, the system demonstrated broad-spectrum contaminant removal capabilities, which could simultaneously eliminate more than 99.7% of oxytetracycline hydrochloride (TCH) and 87.9% of ciprofloxacin (CFX) within 20 min. Additionally, the removal rates for several dyes reached more than 95.7% in 20 min. Phytotoxicity assessment (using mung bean seeds) confirmed a significant reduction in the biotoxicity of post-treatment TC solutions. The identification of TC degradation intermediates was enabled, alongside the subsequent proposal of plausible degradation pathways. Furthermore, mechanistic investigations based on radical quenching experiments revealed the coexistence of dual radical (•OH and

{SO}_{4}^{-} •

) and non-radical (¹O₂) oxidation pathways in the reaction of the CoAl-LDH@BC/PMS system. Overall, this research broadens the potential applications of bacterial cellulose-based porous materials and provides an innovative insight into antibiotic wastewater treatment. Full article

(This article belongs to the Section Natural and Bio-derived Molecules)

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