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Biomolecules, Volume 15, Issue 8 (August 2025) – 11 articles

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28 pages, 2329 KiB  
Review
Myocardial Infarction in Young Adults: A Case Series and Comprehensive Review of Molecular and Clinical Mechanisms
by Bogdan-Sorin Tudurachi, Larisa Anghel, Andreea Tudurachi, Răzvan-Liviu Zanfirescu, Silviu-Gabriel Bîrgoan, Radu Andy Sascău and Cristian Stătescu
Biomolecules 2025, 15(8), 1065; https://doi.org/10.3390/biom15081065 - 23 Jul 2025
Abstract
Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to [...] Read more.
Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to nonatherothrombotic mechanisms such as coronary vasospasm, spontaneous coronary artery dissection (SCAD), vasculitis, hypercoagulable states, and drug-induced coronary injury. This manuscript aims to explore the multifactorial nature of AMI in young adults through a focused review of current evidence and a series of illustrative clinical cases. We present and analyze four distinct cases of young patients with AMI, each demonstrating different pathophysiological mechanisms and risk profiles—including premature atherosclerosis, substance use, human immunodeficiency virus (HIV)-related coronary disease, and SCAD. Despite the heterogeneity of underlying causes, early diagnosis, individualized management, and aggressive secondary prevention were key to favorable outcomes. Advanced imaging, lipid profiling, and risk factor modification played a central role in guiding therapy. AMI in young adults requires heightened clinical suspicion and a comprehensive, multidisciplinary approach. Early intervention and recognition of nontraditional risk factors are essential to improving outcomes and preventing recurrent events in this vulnerable population. Full article
(This article belongs to the Special Issue Cardiometabolic Disease: Molecular Basis and Therapeutic Approaches)
16 pages, 2129 KiB  
Article
A Distinct miRNA Profile in Intimal Hyperplasia of Failed Arteriovenous Fistulas Reveals Key Pathogenic Pathways
by Carmen Ciavarella, Francesco Vasuri, Alessio Degiovanni, Lena Christ, Raffaella Mauro, Mauro Gargiulo and Gianandrea Pasquinelli
Biomolecules 2025, 15(8), 1064; https://doi.org/10.3390/biom15081064 - 23 Jul 2025
Abstract
Intimal hyperplasia (IH) compromises the patency of arteriovenous fistula (AVF) vascular access in patients with end-stage kidney disease. Uncontrolled cell proliferation and migration, driven by inflammation, shear stress and surgery, are well-known triggers in IH. Recently, microRNAs (miRNAs) have emerged as regulators of [...] Read more.
Intimal hyperplasia (IH) compromises the patency of arteriovenous fistula (AVF) vascular access in patients with end-stage kidney disease. Uncontrolled cell proliferation and migration, driven by inflammation, shear stress and surgery, are well-known triggers in IH. Recently, microRNAs (miRNAs) have emerged as regulators of core mechanisms in cardiovascular diseases and as potential markers of IH. This study was aimed at identifying a specific miRNA panel in failed AVFs and clarifying the miRNA involvement in IH. miRNA profiling performed in tissues from patients with IH (AVFs) and normal veins (NVs) highlighted a subset of four miRNAs significantly deregulated (hsa-miR-155-5p, hsa-miR-449a-5p, hsa-miR-29c-3p, hsa-miR-194-5p) between the two groups. These miRNAs were analyzed in tissue-derived cells (NVCs and AVFCs), human aortic smooth muscle cells (HAOSMCs) and human umbilical vein endothelial cells (HUVECs). The panel of hsa-miR-449a-5p, hsa-miR-155-5p, hsa-miR-29c-3p and hsa-miR-194-5p was up-regulated in AVFCs, HAOSMCs and HUVEC under inflammatory stimuli. Notably, overexpression of hsa-miR-449a-5p exacerbated the proliferative, migratory and inflammatory features of AVFCs. In vitro pharmacological modulation of these miRNAs with pioglitazone, particularly the down-regulation of hsa-miR-155-5p and hsa-miR-29c-3p, suggested their involvement in IH pathogenesis and a potential translational application. Overall, these findings provide new insights into the pathogenesis of AVF failure, reinforcing the miRNA contribution to IH detection and prevention. Full article
(This article belongs to the Section Molecular Biology)
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31 pages, 4621 KiB  
Perspective
Current Flow in Nerves and Mitochondria: An Electro-Osmotic Approach
by Robert S. Eisenberg
Biomolecules 2025, 15(8), 1063; https://doi.org/10.3390/biom15081063 - 22 Jul 2025
Abstract
The electrodynamics of current provide much of our technology, from telegraphs to the wired infrastructure powering the circuits of our electronic technology. Current flow is analyzed by its own rules that involve the Maxwell Ampere law and magnetism. Electrostatics does not involve magnetism, [...] Read more.
The electrodynamics of current provide much of our technology, from telegraphs to the wired infrastructure powering the circuits of our electronic technology. Current flow is analyzed by its own rules that involve the Maxwell Ampere law and magnetism. Electrostatics does not involve magnetism, and so current flow and electrodynamics cannot be derived from electrostatics. Practical considerations also prevent current flow from being analyzed one charge at a time. There are too many charges, and far too many interactions to allow computation. Current flow is essential in biology. Currents are carried by electrons in mitochondria in an electron transport chain. Currents are carried by ions in nerve and muscle cells. Currents everywhere follow the rules of current flow: Kirchhoff’s current law and its generalizations. The importance of electron and proton flows in generating ATP was discovered long ago but they were not analyzed as electrical currents. The flow of protons and transport of electrons form circuits that must be analyzed by Kirchhoff’s law. A chemiosmotic theory that ignores the laws of current flow is incorrect physics. Circuit analysis is easily applied to short systems like mitochondria that have just one internal electrical potential in the form of the Hodgkin Huxley Katz (HHK) equation. The HHK equation combined with classical descriptions of chemical reactions forms a computable model of cytochrome c oxidase, part of the electron transport chain. The proton motive force is included as just one of the components of the total electrochemical potential. Circuit analysis includes its role just as it includes the role of any other ionic current. Current laws are now needed to analyze the flow of electrons and protons, as they generate ATP in mitochondria and chloroplasts. Chemiosmotic theory must be replaced by an electro-osmotic theory of ATP production that conforms to the Maxwell Ampere equation of electrodynamics while including proton movement and the proton motive force. Full article
(This article belongs to the Special Issue Advances in Cellular Biophysics: Transport and Mechanics)
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21 pages, 2670 KiB  
Article
Regulatory Effect of PGE2-EP2/EP4 Receptor Pathway on Staphylococcus aureus-Induced Inflammatory Factors in Dairy Cow Neutrophils
by Yi Zhao, Chao Wang, Bo Liu, Shuangyi Zhang, Yongfei Wang, Yinghong Qian, Zhiguo Gong, Jiamin Zhao, Xiaolin Yang, Yuting Bai and Wei Mao
Biomolecules 2025, 15(8), 1062; https://doi.org/10.3390/biom15081062 - 22 Jul 2025
Abstract
Naturally occurring prostaglandin E2 (PGE2) influences cytokine production regulation in bovine neutrophils exposed to Staphylococcus aureus Rosenbach. Here, we employed bovine neutrophils as the primary experimental system, and administered specific inhibitors targeting various receptors, which were subsequently exposed to S. [...] Read more.
Naturally occurring prostaglandin E2 (PGE2) influences cytokine production regulation in bovine neutrophils exposed to Staphylococcus aureus Rosenbach. Here, we employed bovine neutrophils as the primary experimental system, and administered specific inhibitors targeting various receptors, which were subsequently exposed to S. aureus. Cytokine expression levels in dairy cow neutrophils induced by S. aureus via the endogenous PGE2-EP2/4 receptor pathway were investigated, and its effects on P38, extracellular signal-regulated kinase (ERK), P65 activation, and phagocytic function in Staphylococcus aureus Rosenbach-induced dairy cow neutrophils, were examined. Blocking cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) enzymes substantially decreased PGE2 production and release in S. aureus-exposed bovine neutrophils. Cytokine output showed significant reduction compared to that in SA113-infected controls. Phosphorylation of P38, ERK, and P65 signaling molecules was depressed in the infected group. Pharmacological interference with EP2/EP4 receptors similarly diminished cytokine secretion and phosphorylation patterns of P38, ERK, and P65, with preserved cellular phagocytic function. During S. aureus infection of bovine neutrophils, COX-2 and mPGES-1 participated in controlling PGE2 biosynthesis, and internally produced PGE2 molecules triggered NF-κB and MAPK inflammatory pathways via EP2/EP4 receptor activation, later adjusting the equilibrium between cytokine types that promote or suppress inflammation. This signaling mechanism coordinated inflammatory phases through receptor-mediated processes. Full article
(This article belongs to the Section Molecular Biology)
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23 pages, 2985 KiB  
Review
Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities
by Claudio Brancolini
Biomolecules 2025, 15(8), 1061; https://doi.org/10.3390/biom15081061 - 22 Jul 2025
Abstract
Class IIa histone deacetylases (HDACs) are pleiotropic regulators of various differentiation pathways and adaptive responses. They form complexes with other co-repressors and can bind to DNA by interacting with selected transcription factors, with members of the Myocyte Enhancer Factor-2 (MEF2) family being the [...] Read more.
Class IIa histone deacetylases (HDACs) are pleiotropic regulators of various differentiation pathways and adaptive responses. They form complexes with other co-repressors and can bind to DNA by interacting with selected transcription factors, with members of the Myocyte Enhancer Factor-2 (MEF2) family being the best characterized. A notable feature of class IIa HDACs is the substitution of tyrosine for histidine in the catalytic site, which has occurred over the course of evolution and has a profound effect on the efficiency of catalysis against acetyl-lysine. Another distinctive feature of this family of “pseudoenzymes” is the regulated nucleus–cytoplasm shuttling associated with several non-histone proteins that have been identified as potential substrates, including proteins localized in the cytosol. Within the complexity of class IIa HDACs, several aspects deserve further investigation. In the following, I will discuss some of the recent advances in our knowledge of class IIa HDACs. Full article
(This article belongs to the Special Issue Recent Advances in Chromatin and Chromosome Molecular Research)
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29 pages, 1763 KiB  
Review
Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection
by Marcela Montilla, Norma Pavas-Escobar, Iveth Melissa Guatibonza-Arévalo, Alejandro Múnera, Renshen Eduardo Rivera-Melo and Felix A. Ruiz
Biomolecules 2025, 15(8), 1060; https://doi.org/10.3390/biom15081060 - 22 Jul 2025
Abstract
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders [...] Read more.
Inorganic polyphosphate (polyP) is an evolutionarily conserved polymer that has recently gained relevance in neuronal physiology and pathophysiology. Although its roles, such as mitochondrial bioenergetics, calcium homeostasis, and the oxidative stress response, for example, are increasingly recognized, its specific implications in neurological disorders remain underexplored. This review focuses on synthesizing the current knowledge of polyP in the context of central nervous system (CNS) diseases, highlighting how its involvement in key mitochondrial processes may influence neuronal survival and function. In particular, we examine recent evidence linking polyP to mechanisms relevant to neurodegeneration, such as the modulation of the mitochondrial permeability transition pore (mPTP), regulation of amyloid fibril formation, and oxidative stress responses. In addition, we analyze the emerging roles of polyP in inflammation and related cell signaling in CNS disorders. By organizing the existing data around the potential pathological and protective roles of polyP in the CNS, this review identifies it as a candidate of interest in the context of neurodegenerative disease mechanisms. We aim to clarify its relevance and stimulate future research on its molecular mechanisms and translational potential. Full article
(This article belongs to the Special Issue Polyphosphate (PolyP) in Health and Disease)
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26 pages, 1899 KiB  
Review
Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch’s Membrane Pathology and Age-Related Macular Degeneration (AMD)
by Ali A. Hussain and Yunhee Lee
Biomolecules 2025, 15(8), 1059; https://doi.org/10.3390/biom15081059 - 22 Jul 2025
Abstract
The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted [...] Read more.
The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch’s membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch’s membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets. Full article
(This article belongs to the Special Issue Role of Matrix Metalloproteinase in Health and Disease)
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15 pages, 6089 KiB  
Article
Molecular Fingerprint of Cold Adaptation in Antarctic Icefish PepT1 (Chionodraco hamatus): A Comparative Molecular Dynamics Study
by Guillermo Carrasco-Faus, Valeria Márquez-Miranda and Ignacio Diaz-Franulic
Biomolecules 2025, 15(8), 1058; https://doi.org/10.3390/biom15081058 - 22 Jul 2025
Abstract
Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, [...] Read more.
Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function. Our simulations show that ChPepT1 displays enhanced global flexibility, particularly in domains adjacent to the substrate-binding site and the C-terminal domain (CTD). While hPepT1 loses substrate binding affinity as temperature increases, ChPepT1 maintains stable peptide interactions across a broad thermal range. This thermodynamic buffering results from temperature-sensitive rearrangement of hydrogen bond networks and more dynamic lipid interactions. Importantly, we identify a temperature-responsive segment (TRS, residues 660–670) within the proximal CTD that undergoes an α-helix to coil transition, modulating long-range coupling with transmembrane helices. Dynamic cross-correlation analyses further suggest that ChPepT1, unlike hPepT1, reorganizes its interdomain communication in response to temperature shifts. Our findings suggest that cold tolerance in ChPepT1 arises from a combination of structural flexibility, resilient substrate binding, and temperature-sensitive interdomain dynamics. These results provide new mechanistic insight into thermal adaptation in membrane transporters and offer a framework for engineering proteins with enhanced functionality in extreme environments. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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29 pages, 53407 KiB  
Review
Changes in Epithelial Cell Polarity and Adhesion Guide Human Endometrial Receptivity: How In Vitro Systems Help to Untangle Mechanistic Details
by Irmgard Classen-Linke, Volker U. Buck, Anna K. Sternberg, Matthias Kohlen, Liubov Izmaylova and Rudolf E. Leube
Biomolecules 2025, 15(8), 1057; https://doi.org/10.3390/biom15081057 - 22 Jul 2025
Abstract
Tissue remodeling of human endometrium occurs during the menstrual cycle to prepare for embryo adhesion and invasion. The ovarian steroid hormones 17β-estradiol and progesterone control the menstrual cycle to achieve the receptive state during the “window of implantation” (WOI). Here, we focus on [...] Read more.
Tissue remodeling of human endometrium occurs during the menstrual cycle to prepare for embryo adhesion and invasion. The ovarian steroid hormones 17β-estradiol and progesterone control the menstrual cycle to achieve the receptive state during the “window of implantation” (WOI). Here, we focus on the human endometrial epithelium and its changes in polarity, adhesion, cytoskeletal organization and the underlying extracellular matrix enabling embryo implantation. The adhesion and invasion of the trophoblast via the apical plasma membrane of epithelial cells is a unique cell biological process, which is coupled to partial epithelial–mesenchymal transition (EMT). Given the fundamental species differences during implantation, we restrict the review mainly to the human situation and focus on cell culture systems to study the interaction between human trophoblast and endometrial cells. We summarize current knowledge based on the relatively scarce in vivo data and the steadily growing in vitro observations using various cell culture systems. Full article
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14 pages, 1573 KiB  
Article
Association of 17q12-q21 Asthma Risk Locus with Clinical Severity of Infant Respiratory Syncytial Virus Infection
by Kedir N. Turi, Christopher McKennan, Christian Rosas-Salazar, Tebeb Gebretsedik, Dawn C. Newcomb, Emma E. Thompson, James Gern, James Chappell, Larry Anderson, Carole Ober and Tina Hartert
Biomolecules 2025, 15(8), 1056; https://doi.org/10.3390/biom15081056 - 22 Jul 2025
Abstract
This study examined whether SNPs at the 17q12-q21 locus that are associated with childhood asthma are also associated with severe respiratory syncytial virus (RSV) infection and viral load. We conducted a candidate SNP association study in the subset of RSV-infected infants who were [...] Read more.
This study examined whether SNPs at the 17q12-q21 locus that are associated with childhood asthma are also associated with severe respiratory syncytial virus (RSV) infection and viral load. We conducted a candidate SNP association study in the subset of RSV-infected infants who were parent-identified as White (n = 159) in the INSPIRE cohort. Nine SNPs at the 17q12-q21 locus were genotyped. We used an additive model to evaluate each SNP’s association with RSV infection severity and viral load. Replication of significant associations was tested in the TCRI cohort: infants with severe RSV illness. In INSPIRE, an SNP rs8069202-G in the GSDMA gene was associated with increased RSV viral load (and marginally associated with RSV severity). SNP rs2941504, in the PGAP3 gene, was associated with a reduced risk of RSV severity. All significant associations were directionally replicated in the TCRI cohort but were insignificant at a p-value < 0.05. The association of a SNP in GSDMA with RSV viral load and RSV infection severity suggests that GSDMA may be contributing to both severe RSV infection and asthma development. On the other hand, the association between an SNP in PGAP3 and reduced RSV infection severity suggests distinct pathways link PGAP3 to these two respiratory outcomes. Full article
(This article belongs to the Section Molecular Medicine)
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31 pages, 4179 KiB  
Review
Plant-Derived Vesicle-like Nanoparticles: Pioneering Sustainable and Effective Approaches for Tissue Repair and Regeneration
by Qinjing Wang, Zhijie Huang, Jiming Guo, Weixing Chen, Min Wang, Yue Ming, Hongyu Liu, Mingshu Huang, Yisheng Huang, Zhengming Tang and Bo Jia
Biomolecules 2025, 15(8), 1055; https://doi.org/10.3390/biom15081055 - 22 Jul 2025
Abstract
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, [...] Read more.
Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
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